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Simple Summary: Heat stress during pregnancy can negatively affect the intrauterine environment, compromising fetal development and resulting in long-term physiological and structural changes that impact the postnatal outcomes of the offspring. The aim of this retrospective longitudinal study was to identify how exposure to summer season at different trimesters of intrauterine development and dam parity affect postpartum disease incidence, milk production, and herd lifespan of the offspring (F1 generation) of Holstein cows. Our preliminary findings confirmed less milk production capacity and greater culling risk in offspring experiencing the summer season during the first trimester of their intrauterine development than those during later stages. Daughters born to nulliparous dams had a lower risk of dystocia and metritis, a higher risk of retained placenta, and were more likely to remain in the herd than those born to parous dams. Minimizing summer heat exposure during the early intrauterine development of offspring through implementing heat-abatement strategies may help alleviate the risk of future production losses. A suboptimal intrauterine environment during gestation may result in the programming of long-lasting structural and physiological alterations in the developing fetus, leading to health and production complications in adulthood. This observational study aimed to identify the impact of exposure to the summer season at different trimesters of gestation, dam parity, and their interaction on the postpartum disease incidence, first-lactation milk production, and herd lifespan of the offspring (F1 generation). Using a dataset collected from two commercial herds, the female offspring were categorized into three groups based on the trimester their dams experienced summer season during pregnancy: (1) first trimester (n = 2345), (2) second trimester (n = 3513), and (3) final trimester (n = 4988). The estimated 305-day milk production was lower in daughters (as a first-lactation cow) born to dams exposed to summer season during the first vs. third trimester. Summer season exposure during the first vs. third trimester resulted in the offspring that were less likely to remain in the herd (hazard ratio = 0.90; 95% CI = 0.84–0.95). Daughters of parous vs. nulliparous dams were more likely to experience dystocia and metritis but less likely to experience retained placenta. The risk of culling was higher in daughters of parous vs. nulliparous dams. Our preliminary findings suggest that the first trimester is a critical determinant of the female progeny's future productive performance and survivability. Dam parity was also identified as an influential factor affecting offspring health, as dystocia and metritis were more prevalent, and the culling risk was greater in daughters born to parous dams. [ABSTRACT FROM AUTHOR]

Level of dam milk production (DMP) and dam milk fat to protein ratio (DFPR), as an indicator of metabolic status in dairy cows, have been identified to be associated with productive and reproductive performance of the offspring. Yet whether the interaction of DMP by DFPR can be associated with performance of the offspring have not been studied to our knowledge. Therefore, the present study was conducted to investigate the association of the main and interactive effects of DMP and DFPR with offspring's birth weight, survival, milk yield and fertility. To this end, data of birth weight, culling rate, milk yield and reproductive variables of offspring born to lactating dams (n = 14,582) and data associated with DMP and DFPR during 305-day lactation were retrieved. Afterwards, offspring were classified in three categories of DMP, including DMP1 (dams with <10.00 × 103 kg of 305-day milk production), DMP2 (dams with ≥10.00 × 103 kg and <14.00 × 103 kg of 305-day milk production), DMP3 (dams with ≥14.00 × 103 kg of 305-day milk production), and three categories of DFPR, including DFPR1 (offspring born to dams with <1.00 FPR), DFPR2 (offspring born to dams with ≥1.00 and < 1.40 FPR) and DFPR3 (offspring born to dams with ≥1.40 FPR). Statistical analysis revealed no association of the interaction effect of DMP by DFPR with investigated variables in the offspring (P > 0.05). However, the main effect of DMP was positively associated with milk yield, but negatively associated with survival, age at first insemination and conception during nulliparity, and transgenerational improvement in milk yield in the offspring (P < 0.05). Moreover, the main effect of DFPR was positively associated with birth weight, survival and first service conception rate during nulliparity, but negatively associated with metabolic status and reproductive performance during primiparity in the offspring (P < 0.05). In conclusion, the present study did not find any interaction effect of DMP by DFPR on productive and reproductive variables in the offspring. This finding implicates the association of DMP with milk production in the offspring was regardless of DFPR. Moreover, this finding implies the association of DFPR with postpartum metabolic status and reproductive performance in the offspring was regardless of DMP. • The interaction effect of dam milk production (DMP) by dam fat to protein ratio (DFPR) was not associated with productive and reproductive performance of the offspring. • Although the main effect of DMP was positively associated with milk production of the offspring, it was negatively associated with transgenerational improvement in milk production. • The main effect of DFPR was associated with postpartum metabolic status and reproductive performance of the offspring. [ABSTRACT FROM AUTHOR]

Background: Pregnancy represents a window of vulnerability to fetal development. Disruptions in the prenatal environment during this crucial period can increase the risk of the offspring developing diseases over the course of their lifetime. The central nervous system (CNS) has been shown to be particularly susceptible to changes during crucial developmental windows. To date, research focused on disruptions in the development of the CNS has predominantly centred on the brain, revealing a correlation between exposure to prenatal risk factors and the onset of neuropsychiatric disorders. Nevertheless, some studies indicate that the retina, which is part of the CNS, is also vulnerable to in utero alterations during pregnancy. Such changes may affect neuronal, glial and vascular components of the retina, compromising retinal structure and function and possibly impairing visual function. Methods: A search in the PubMed database was performed, and any literature concerning prenatal risk factors (drugs, diabetes, unbalanced diet, infection, glucocorticoids) affecting the offspring retina were included. Results: This review collects evidence on the cellular, structural and functional changes occurring in the retina triggered by maternal risk factors during pregnancy. We highlight the adverse impact on retinal development and its long‐lasting effects, providing a critical analysis of the current knowledge while underlining areas for future research. Conclusions: Appropriate recognition of the prenatal risk factors that negatively impact the developing retina may provide critical clues for the design of preventive strategies and for early therapeutic intervention that could change retinal pathology in the progeny. [ABSTRACT FROM AUTHOR]

Women with polycystic ovary syndrome (PCOS) exhibit sustained elevation in circulating androgens during pregnancy, an independent risk factor linked to pregnancy complications and adverse outcomes in offspring. Yet, further studies are required to understand the effects of elevated androgens on cell type‐specific placental dysfunction and fetal development. Therefore, a PCOS‐like mouse model induced by continuous androgen exposure is examined. The PCOS‐mice exhibited impaired placental and embryonic development, resulting in mid‐gestation lethality. Co‐treatment with the androgen receptor blocker, flutamide, prevents these phenotypes including germ cell specification. Comprehensive profiling of the placenta by whole‐genome bisulfite and RNA sequencing shows a reduced proportion of trophoblast precursors, possibly due to the downregulation of Cdx2 expression. Reduced expression of Gcm1, Synb, and Prl3b1 is associated with reduced syncytiotrophoblasts and sinusoidal trophoblast giant cells, impairs placental labyrinth formation. Importantly, human trophoblast organoids exposed to androgens exhibit analogous changes, showing impaired trophoblast differentiation as a key feature in PCOS‐related pregnancy complications. These findings provide new insights into the potential cellular targets for future treatments. [ABSTRACT FROM AUTHOR]

Environmental factors in the early life stages can lead the descendant to adaptations in gene expression, permanently impacting several structures and organs. The amount and quality of fatty acids in the maternal diet in pregnancy and lactation were found to impact offspring metabolism. So, maternal diet and insulin resistance can affect the male and female descendants through distinct pathways and at different time points. We hypothesized that maternal high-fat diet (HFD) intake before conception and an adequate amount of different fatty acids intake during pregnancy and lactation could influence the energy homeostasis system of 21-day-old offspring. Female rats received control diet (C) or HFD (HF) for 8 weeks before pregnancy. During pregnancy and lactation C group remained with same diet (C-C), HF group were distributed into 4 groups and received C diet (HF-C), normolipidic diet based on saturated fatty acids (HF-S) or based on polyunsaturated fatty acids n-3 (HF-P) or remained in same diet (HF-HF). Maternal HFD in preconception, pregnancy, and lactation (HF-HF) led to lower glucagon-like peptide-1 levels in male (HF-HF21) compared to other groups (C-C21, HF-C21, and HF-P21) and compared to HF-HF21 females. Neuropeptide YY levels were higher in the HF-HF21, HF-C21, and HF-S21 male offspring compared to HF-P21. HF-P21 was similar to C-C21. Positive correlations were found among the energy homeostasis markers genes expressed in the offspring hypothalamus. Maternal diet changes to adequate quantities of fatty acids during pregnancy and lactation showed less impaired results but was not entirely avoided. A maternal diet based on PUFA n-3 during pregnancy and lactation seems to reverse the damage of an HFD in preconception. These results of homeostasis energy system disturbance in the offspring at weaning give us clues about changes that precede the onset of the disease in adult life — adding notes to the knowledge for future investigations of prevention and treatment of chronic diseases. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. The performance of an adult dairy cow may be influenced by events that occur before her birth. The present study investigated the potential effects of 2 prenatal groups of factors, assisted reproductive technologies and maternal characteristics (e.g., dam parity), on offspring performance during their first lactation in populations of 2 dairy cow breeds: French Holstein and Montbéliarde. The different assisted reproductive technologies studied included the type of semen (conventional or X-sorted) used for AI and the technology of conception used (AI, embryo transfer, or in vitro fertilization). Three maternal characteristics were considered: (1) the dam age at first calving, (2) dam parity number, and (3) indicators of dam udder health during gestation (SCS and events of clinical mastitis). First, we investigated whether heifer survival from 3 d to 18 mo old was associated with any of the prenatal factors considered. We then estimated the associations of these prenatal factors with 8 traits of commercial interest: (1) stature, (2–4) milk, fat, and protein yields, (5) SCS, (6) clinical mastitis, and (7–8) heifer and cow conception rate, all measured on genotyped cows. Linear models were used for this study with the prenatal factors as covariates in the model, and for the 8 traits, phenotypes were adjusted for their corresponding genomic EBV. The results indicated that the survival rate of heifers born from embryo transfer was significantly higher than that of heifers born from AI (probably due to preferential management practices), and the other prenatal factors did not explain large differences in heifer survival. Among the Montbéliarde cows born from AI, those born from X-sorted semen showed a lightly but significantly lower milk yield than those born without X-sorting of the semen (−52 kg of milk in the first lactation). Among the Holstein cows, those born from embryo transfer presented significantly lower milk performance than cows born from AI. Regarding the maternal characteristics, none or very weak associations were found between the dam age at first calving and the offspring performance in both breeds. Dam parity, on the other hand, was associated with offspring performance for milk, fat, and protein yield in both breeds, but not in the same direction. In the Holstein breed, an increase in dam parity was favorable for offspring performance for milk, fat, and protein yield, whereas in the Montbéliarde breed, an increase in dam parity was associated with lower milk and protein yield and no association was found for fat yield. The udder health of the dam during gestation was not or only weakly associated with the traits studied in the offspring. Although some significant associations were identified due to the large sample size, the effects were modest, typically less than 1% of the phenotypic mean, and were not consistently observed across the 2 breeds. [ABSTRACT FROM AUTHOR]

Fetal growth restriction (FGR) is a common outcome in human suboptimal gestation and is related to prenatal origins of cardiovascular dysfunction in offspring. Despite this, therapy of human translational potential has not been identified. Using human umbilical and placental vessels and the chicken embryo model, we combined cellular, molecular, and functional studies to determine whether N‐acetylcysteine (NAC) and hydrogen sulphide (H2S) protect cardiovascular function in growth‐restricted unborn offspring. In human umbilical and placental arteries from control or FGR pregnancy and in vessels from near‐term chicken embryos incubated under normoxic or hypoxic conditions, we determined the expression of the H2S gene CTH (i.e. cystathionine γ‐lyase) (via quantitative PCR), the production of H2S (enzymatic activity), the DNA methylation profile (pyrosequencing) and vasodilator reactivity (wire myography) in the presence and absence of NAC treatment. The data show that FGR and hypoxia increased CTH expression in the embryonic/fetal vasculature in both species. NAC treatment increased aortic CTH expression and H2S production and enhanced third‐order femoral artery dilator responses to the H2S donor sodium hydrosulphide in chicken embryos. NAC treatment also restored impaired endothelial relaxation in human third‐to‐fourth order chorionic arteries from FGR pregnancies and in third‐order femoral arteries from hypoxic chicken embryos. This NAC‐induced protection against endothelial dysfunction in hypoxic chicken embryos was mediated via nitric oxide independent mechanisms. Both developmental hypoxia and NAC promoted vascular changes in CTH DNA and NOS3 methylation patterns in chicken embryos. Combined, therefore, the data support that the effects of NAC and H2S offer a powerful mechanism of human translational potential against fetal cardiovascular dysfunction in complicated pregnancy. Key points: Gestation complicated by chronic fetal hypoxia and fetal growth restriction (FGR) increases a prenatal origin of cardiovascular disease in offspring, increasing interest in antenatal therapy to prevent against a fetal origin of cardiovascular dysfunction.We investigated the effects between N‐acetylcysteine (NAC) and hydrogen sulphide (H2S) in the vasculature in FGR human pregnancy and in chronically hypoxic chicken embryos.Combining cellular, molecular, epigenetic and functional studies, we show that the vascular expression and synthesis of H2S is enhanced in hypoxic and FGR unborn offspring in both species and this acts to protect their vasculature.Therefore, the NAC/H2S pathway offers a powerful therapeutic mechanism of human translational potential against fetal cardiovascular dysfunction in complicated pregnancy. [ABSTRACT FROM AUTHOR]

Maternal obesity, caused by diets rich in fats and sugars during pregnancy, can predispose offspring to metabolic diseases such as diabetes. We hypothesized that obesity during pregnancy leads to increased DNA methylation and reduced protein expression in factors regulating β-cell function and apoptosis. Female C57BL/6J mice were fed a high-fat diet (HFD; 42% fat content; n = 3) or a control diet (CON; 16% fat content; n = 3) for fourteen weeks before and during pregnancy. Offspring were euthanized at 8 weeks and pancreatic tissue was collected. Isolated DNA was analyzed using whole-genome bisulfite sequencing. Protein expression was quantified using LC–MS. No significant differences in body weight were observed between HFD and control pups (p = 0.10). Whole-genome bisulfite sequencing identified 91,703 and 88,415 differentially methylated regions (DMRs) in CON vs. HFD male and female offspring. A total of 34 and 4 proteins were determined to have changes in expression that correlated with changes in DNA methylation in CON vs. HFD males and females, respectively. The majority of these factors were grouped into the metabolic function category via pathway analyses. This study illustrates the complex relationship between epigenetics, diet, and sex-specific responses, therefore offering insights into potential therapeutic targets and areas for further research. [ABSTRACT FROM AUTHOR]

Context: A maternal high-fat diet is thought to pose a risk to spermatogenesis in the progeny. Aims: We tested whether a maternal high-fat diet would affect Sertoli cell expression of transcription factors (insulin-like growth factor I (IGF-I); glial-cell line-derived neurotrophic factor (GDNF); Ets variant 5 (ETV5)) and cell proliferation and apoptotic proteins, in the testis of adult offspring. Methods: Pregnant rats were fed ad libitum with a standard diet (Control) or a high-fat diet (HFat) throughout pregnancy and lactation. After weaning, male pups were fed the standard diet until postnatal day 160. Males were monitored daily from postnatal day 34 to determine onset of puberty. On postnatal day 160, their testes were processed for morphometry and immunohistochemistry. Key results: The HFat diet increased seminiferous-tubule diameter (P < 0.03), the numbers of Sertoli cells (P < 0.0001) and Ki-67-positive spermatogonia (P < 0.0006), and the areas immunostained for ETV5 (P < 0.0001), caspase-3 (P < 0.001) and Bcl-2 (P < 0.0001). By contrast, the HFat diet reduced the areas immunostained for IGF-I (P < 0.01) and GDNF (P < 0.0001). Conclusions: A maternal high-fat diet alters the balance between spermatogonia proliferation and spermatid apoptosis. Implications: A maternal high-fat diet seems to 'program' adult male fertility. In rats, we tested whether a high-fat diet fed to mothers during pregnancy and lactation would affect Sertoli cell function in their adult offspring. Changes in transcription factors and proteins that control proliferation and apoptosis in germ cells suggest that the high-fat diet alters the balance between cell proliferation and apoptosis, potentially reducing sperm production. Image by Graciela Pedrana, Grame Martin. [ABSTRACT FROM AUTHOR]

Background: Diabetes in pregnancy is associated with increased risk of long-term metabolic disease in the offspring, potentially mediated by in utero epigenetic variation. Previously, we identified multiple differentially methylated single CpG sites in offspring of women with gestational diabetes mellitus (GDM), but whether stretches of differentially methylated regions (DMRs) can also be identified in adolescent GDM offspring is unknown. Here, we investigate which DNA regions in adolescent offspring are differentially methylated in blood by exposure to diabetes in pregnancy. The secondary aim was to characterize the RNA expression of the identified DMR, which contained the nc886 non-coding RNA. Methods: To identify DMRs, we employed the bump hunter method in samples from young (9–16 yr, n = 92) offspring of women with GDM (O-GDM) and control offspring (n = 94). Validation by pyrosequencing was performed in an adult offspring cohort (age 28–33 years) consisting of O-GDM (n = 82), offspring exposed to maternal type 1 diabetes (O-T1D, n = 67) and control offspring (O-BP, n = 57). RNA-expression was measured using RT-qPCR in subcutaneous adipose tissue and skeletal muscle. Results: One significant DMR represented by 10 CpGs with a bimodal methylation pattern was identified, located in the nc886/VTRNA2-1 non-coding RNA gene. Low methylation status across all CpGs of the nc886 in the young offspring was associated with maternal GDM. While low methylation degree in adult offspring in blood, adipose tissue, and skeletal muscle was not associated with maternal GDM, adipose tissue nc886 expression was increased in O-GDM compared to O-BP, but not in O-T1D. In addition, adipose tissue nc886 expression levels were positively associated with maternal pre-pregnancy BMI (p = 0.006), but not with the offspring's own adiposity. Conclusions: Our results highlight that nc886 is a metastable epiallele, whose methylation in young offspring is negatively correlated with maternal obesity and GDM status. The physiological effect of nc886 may be more important in adipose tissue than in skeletal muscle. Further research should aim to investigate how nc886 regulation in adipose tissue by exposure to GDM may contribute to development of metabolic disease. [ABSTRACT FROM AUTHOR]

Although the association of maternal milk production with developmental programming of offspring has been investigated, there is limited information available on the relationship of maternal milk components with productive and reproductive performance of the offspring. Therefore, the present study was conducted to analyze the association of maternal milk fat and protein percentage and milk fat to protein ratio with birth weight, survival, productive and reproductive performance and AMH concentration in the offspring. In study I, data of birth weight, milk yield and reproductive variables of offspring born to lactating dams (n = 14,582) and data associated with average maternal milk fat percentage (MFP), protein percentage (MPP) and fat to protein ratio (MFPR) during 305-day lactation were retrieved. Afterwards, offspring were classified in various categories of MFP, MPP and MFPR. In study II, blood samples (n = 339) were collected from offspring in various categories of MFP, MPP and MFPR for measurement of serum AMH. Maternal milk fat percentage was positively associated with birth weight and average percentage of milk fat (APMF) and protein (APMP) and milk fat to protein ratio (FPR) during the first lactation, but negatively associated with culling rate during nulliparity in the offspring (P < 0.05). Maternal milk protein percentage was positively associated with birth weight, APMF, APMP, FPR and culling rate, but negatively associated with milk yield and fertility in the offspring (P < 0.05). Maternal FPR was positively associated with APMF and FPR, but negatively associated with culling rate, APMP and fertility in the offspring (P < 0.05). However, concentration of AMH in the offspring was not associated with MFP, MPP and MFPR (P > 0.05). In conclusion, the present study revealed that maternal milk fat and protein percentage and their ratio were associated with birth weight, survival, production and reproduction of the offspring. Yet it was a preliminary research and further studies are required to elucidate the mechanisms underlying these associations. • Maternal milk fat percentage was positively associated with birth weight, average percentage of milk fat and protein, and milk fat to protein ratio (FPR), but negatively associated with culling rate in the offspring. • Maternal milk protein percentage was positively associated with birth weight, average percentage of milk fat and protein, FPR and culling rate, but negatively associated with milk yield and fertility in the offspring. • Maternal FPR was positively associated with average percentage of milk fat and FPR, but negatively associated with culling rate, average percentage of milk protein and fertility in the offspring. [ABSTRACT FROM AUTHOR]

Although obesity is recognized as a risk factor for cardiorenal and metabolic diseases, the impact of parental obesity on the susceptibility of their offspring to renal injury at adulthood is unknown. We examined the impact of parental obesity on offspring kidney function, morphology, and markers of kidney damage after acute kidney injury (AKI). Offspring from normal (N) diet-fed C57BL/6J parents were fed either N (NN) or a high-fat (H) diet (NH) from weaning until adulthood. Offspring from obese H diet-fed parents were fed N (HN) or H diet (HH) after weaning. All offspring groups were submitted to bilateral AKI by clamping the left and right renal pedicles for 30 min. Compared with male NH and NN offspring from lean parents, male HH and HN offspring from obese parents exhibited higher kidney injury markers such as urinary, renal osteopontin, plasma creatinine, urinary albumin excretion, and neutrophil gelatinase-associated lipocalin (NGAL) levels, and worse histological injury score at 22 wk of age. Only albumin excretion and NGAL were elevated in female HH offspring from obese parents compared with lean and obese offspring from lean parents. We also found an increased mortality rate and worse kidney injury scores after AKI in male offspring from obese parents, regardless of the diet consumed after weaning. Female offspring were protected from major kidney injury after AKI. These results indicate that parental obesity leads to increased kidney injury in their offspring after ischemia-reperfusion in a sex-dependent manner, even when their offspring remain lean. [ABSTRACT FROM AUTHOR]

Anti-Müllerian hormone (AMH) is an important component within androgen receptor (AR)-regulated pathways governing the hyperandrogenic origin of polycystic ovary syndrome (PCOS). In women with PCOS, granulosa cell AMH overexpression in developing ovarian follicles contributes to elevated circulating AMH levels beginning at birth and continuing in adolescent daughters of PCOS women. A 6 to 7% incidence among PCOS women of gene variants coding for AMH or its receptor, AMHR2, suggests genetic contributions to AMH-related pathogenesis. Discrete gestational AMH administration to pregnant mice induces hypergonadotropic hyperandrogenic, PCOS-like female offspring with high circulating AMH levels that persist over three generations, suggesting epigenetic contributions to PCOS through developmental programming. Moreover, adult-onset, selective hyperactivation of hypothalamic neurons expressing gonadotropin-releasing hormone (GnRH) induces hypergonadotropic hyperandrogenism and PCOS-like traits in female mice. Both gestational and adult AMH inductions of PCOS-like traits are prevented by GnRH antagonist coadministration, implicating luteinizing hormone–dependent ovarian theca cell testosterone (T) action, mediated through the AR in AMH-induced pathogenesis. Interestingly, gestational or peripubertal exogenous T or dihydrotestosterone induction of PCOS-like traits in female mice, rats, sheep, and monkeys fails to elicit ovarian AMH hypersecretion; thus, AMH excess per se may lead to a distinct pathogenic contribution to hyperandrogenic PCOS origins. [ABSTRACT FROM AUTHOR]

Aim: Offspring of obese mothers are at high risk of developing metabolic syndrome and cognitive disabilities. Impaired metabolism has also been reported in the offspring of obese fathers. However, whether brain function can also be affected by paternal obesity has barely been examined. This study aimed to characterize the learning deficits resulting from paternal obesity versus those induced by maternal obesity and to identify the underlying mechanisms. Methods: Founder control and obese female and male Wistar rats were mated to constitute three first‐generation (F1) experimental groups: control mother/control father, obese mother/control father, and obese father/control mother. All F1 animals were weaned onto standard chow and underwent a learning test at 4 months of age, after which several markers of glutamate‐mediated synaptic plasticity together with the expression of miRNAs targeting glutamate receptors and the concentration of kynurenic and quinolinic acids were quantified in the hippocampus and frontal cortex. Results: Maternal obesity induced a severe learning deficit by impairing memory encoding and memory consolidation. The offspring of obese fathers also showed reduced memory encoding but not impaired long‐term memory formation. Memory deficits in offspring of obese fathers and obese mothers were associated with a down‐regulation of genes encoding NMDA glutamate receptors subunits and several learning‐related genes along with impaired expression of miR‐296 and miR‐146b and increased concentration of kynurenic acid. Conclusion: Paternal and maternal obesity impair offspring's learning abilities by affecting different processes of memory formation. These cognitive deficits are associated with epigenetic and neurochemical alterations leading to impaired glutamate‐mediated synaptic plasticity. [ABSTRACT FROM AUTHOR]

Although some studies investigated the relationship of dam milk production (DMP) with offspring birth weight and productive performance, limited information is available on the association of level of DMP with reproductive performance in dairy cows. Therefore, the present study was conducted to understand whether dams with various levels of milk production produce offspring with different fertility. In study I, offspring were classified based on the level of DMP into five categories, including DMP1 (dams with <10.00 × 103 kg of 305-day milk production), DMP2 (dams with ≥10.00 × 103 kg and <12.00 × 103 kg of 305-day milk production), DMP3 (dams with ≥12.00 × 103 kg and <14.00 × 103 kg of 305-day milk production), DMP4 (dams with ≥14.00 × 103 kg and <16.00 × 103 kg of 305-day milk production) and DMP5 (dams with ≥16.00 × 103 kg of 305-day milk production). In study I, data of birth weight, milk yield and reproductive variables of 14,536 offspring born to lactating dams and corresponding data of DMP were retrieved. In study II, blood samples (n = 339) were collected from offspring in various categories of DMP for measurement of serum AMH. Offspring were heavier at birth in DMP4 and DMP5 categories than DMP1 and DMP2 categories (P < 0.05). Milk yield of offspring increased as DMP elevated (P < 0.05); however, offspring in DMP1 and DMP2 categories produced higher milk as compared with their dams during primiparity (P < 0.05) whereas offspring in DMP3, DMP4 and DMP5 categories produced less milk as compared with their dams during primiparity (P < 0.05). Milk fat to protein ratio during the first month of lactation was greater in DMP4 and DMP5 categories than DMP1 category (P < 0.05). Offspring of DMP4 and DMP5 categories were inseminated and conceived at younger ages than offspring of DMP1 category during nulliparity (P < 0.05). Calving to conception interval was longer in DMP5 than DMP1 category in primiparous offspring (P < 0.05), but concentration of AMH did not differ among various categories of DMP (P > 0.05). In conclusion, dams with greater level of milk production produced heavier offspring with higher milk yield but worse transgenerational improvement in milk production and diminished reproductive performance, which were seemingly under higher pressure of negative energy balance during the first month of lactation. • Level of dam milk production (DMP) was positively associated with birth weight of offspring. • Level of DMP was negatively associated with potential for milk production of offspring. • Level of DMP was negatively associated with metabolic status of primiparous offspring during early postpartum period. • Level of DMP was negatively associated with reproductive performance of primiparous offspring. • Level of DMP was not associated with AMH concentration of offspring. [ABSTRACT FROM AUTHOR]

Adverse environmental conditions before birth are known to programme adult metabolic and endocrine phenotypes in several species. However, whether increments in fetal cortisol concentrations of the magnitude commonly seen in these conditions can cause developmental programming remains unknown. Thus, this study investigated the outcome of physiological increases in fetal cortisol concentrations on glucose-insulin dynamics and pituitary-adrenal function in adult sheep. Compared with saline treatment, intravenous fetal cortisol infusion for 5 days in late gestation did not affect birthweight but increased lamb body weight at 1-2 weeks after birth. Adult glucose dynamics, insulin sensitivity and insulin secretion were unaffected by prenatal cortisol overexposure, assessed by glucose tolerance tests, hyperinsulinaemic-euglycaemic clamps and acute insulin administration. In contrast, prenatal cortisol infusion induced adrenal hypo-responsiveness in adulthood with significantly reduced cortisol responses to insulin-induced hypoglycaemia and exogenous adrenocorticotropic hormone (ACTH) administration relative to saline treatment. The area of adrenal cortex expressed as a percentage of the total cross-sectional area of the adult adrenal gland was also lower after prenatal cortisol than saline infusion. In adulthood, basal circulating ACTH but not cortisol concentrations were significantly higher in the cortisol than saline-treated group. The results show that cortisol overexposure before birth programmes pituitary-adrenal development with consequences for adult stress responses. Physiological variations in cortisol concentrations before birth may, therefore, have an important role in determining adult phenotypical diversity and adaptability to environmental challenges. [ABSTRACT FROM AUTHOR]

Perinatal exposure to selective serotonin reuptake inhibitors (SSRIs) has been shown to disrupt the development of serotonergic signaling pathways in the brain and enteric nervous system. Serotonin (5-hydroxytryptamine; 5-HT) signaling is critical for gastrointestinal homeostasis; changes in 5-HT expression and regulation have been associated with gastrointestinal diseases of motility and inflammation. We tested the hypothesis that perinatal exposure to the SSRI fluoxetine can influence the development of the gastrointestinal tract in exposed offspring. Female nulliparous Wistar rats were given fluoxetine (10 mg/kg) or vehicle control from 2 wk before mating until weaning; small and large intestines of female and male offspring were collected at postnatal days 1, 21 (P1, P21, respectively), and 6 mo of age. In histological preparations, the proportion of serotonergic neurons significantly increased in the colons of both female and male fluoxetine-exposed compared with control offspring at P21, a time point that signifies maximal exposure to fluoxetine. At 6 mo of age, male but not female fluoxetine-exposed offspring had a significant increase in circulating 5-HT, with a significant decrease in transcripts encoding the 5-HT2A receptor and monoamine oxidase as compared with control offspring. Measurement of spatiotemporal mapping of contractile activity of the small and large intestine at 6 mo of age revealed no changes in motility in the small bowel of fluoxetine-exposed offspring but revealed a significant increase in the frequency of colonic contractions in the female fluoxetine-exposed compared with control animals. Susceptibility to inflammation was examined at 6 mo using the dextran sulfate sodium model of acute colitis. In utero exposure to fluoxetine was not found to exacerbate colitis severity. These findings suggest that fluoxetine exposure during fetal and early postnatal development can lead to changes in serotonergic neurons at the peak of exposure with sex-specific changes in 5-HT signaling and colonic motility in adulthood. NEW & NOTEWORTHY There is increasing recognition of the relevance of in utero and early postnatal exposures in the developmental programming of the gastrointestinal tract. Perinatal exposure to selective serotonin reuptake inhibitors and antidepressant medications is of particular relevance as they are commonly prescribed during pregnancy, and serotonergic pathways play key roles during gastrointestinal development and in postnatal homeostasis. Here, we provide a comprehensive evaluation of clinically relevant outcomes of gastrointestinal motility and susceptibility to colitis in fluoxetine-exposed offspring and highlight changes in colonic serotonergic neurons at the peak of perinatal fluoxetine exposure with sex-dependent changes in serotonin signaling and colonic motility in adulthood. [ABSTRACT FROM AUTHOR]

Although the negative effect of maternal exposure to heat stress on production and reproduction of offspring has been reported, there are some discrepancies among various studies about which gestational stage is more critical in this regard. Therefore, the present research was conducted to identify during which stage(s) of pregnancy maternal exposure to heat stress would lead to more dramatic decrease in productive and reproductive performance of offspring. To this end, offspring were classified based on the gestational stage they were in utero exposed to heat stress into four categories, including heat stress exposure (HSE) during only the first trimester of gestation (HSE1), HSE during the first and second trimester of gestation (HSE2), HSE during the second and third trimester of gestation (HSE3) and HSE during only the third trimester of gestation (HSE4). In study I, data of birth weight, milk yield and reproductive variables of 11,788 offspring and data of the month they were conceived were retrieved. In study II, blood samples (n = 521) were collected from offspring in various categories of HSE for measurement of serum AMH. Offspring in HSE1 and HSE2 categories were heavier than offspring in HSE3 and HSE4 categories (P < 0.0001). Offspring in HSE1 and HSE3 categories had the lowest and highest milk production, respectively (P < 0.05). First service conception rate was the greatest and worst in HSE1 and HSE4 categories, respectively (P < 0.05). Service per conception and calving to conception interval were greater in HSE2 than HSE4 category (P < 0.05). Concentration of AMH was lower in HSE1 than HSE4 category (P < 0.05). In conclusion, the present study indicated that the early stage of gestation could be a more critical period for the negative impact of in utero heat stress on developmental programming of milk production and ovarian reserves. Yet an evident temporal pattern for the adverse effect of maternal heat stress on developmental programming of reproductive performance in offspring was not found. • Offspring exposed to in utero heat stress (IUHS) during late fetal period had lower birth weight. • Offspring exposed to IUHS during early fetal period, particularly the first month, had lower milk production. • Offspring exposed to IUHS during early fetal period had lower concentration of AMH. • Offspring exposed to IUHS during early fetal period, particularly the first month, had greater first service conception rate. • Offspring exposed to IUHS during early to mid fetal period had greater service per conception and calving to conception interval. [ABSTRACT FROM AUTHOR]

Early-life malnutrition plays a critical role in foetal development and predisposes to metabolic diseases later in life, according to the concept of 'developmental programming'. Different types of early nutritional imbalance, including undernutrition, overnutrition and micronutrient deficiency, have been related to long-term metabolic disorders. Accumulating evidence has demonstrated that disturbances in nutrition during the period of preconception, pregnancy and primary infancy can affect mitochondrial function and epigenetic mechanisms. Moreover, even though multiple mechanisms underlying non-alcoholic fatty liver disease (NAFLD) have been described, in the past years, special attention has been given to mitochondrial dysfunction and epigenetic alterations. Mitochondria play a key role in cellular metabolic functions. Dysfunctional mitochondria contribute to oxidative stress, insulin resistance and inflammation. Epigenetic mechanisms have been related to alterations in genes involved in lipid metabolism, fibrogenesis, inflammation and tumorigenesis. In accordance, studies have reported that mitochondrial dysfunction and epigenetics linked to early-life nutrition can be important contributing factors in the pathogenesis of NAFLD. In this review, we summarise the current understanding of the interplay between mitochondrial dysfunction, epigenetics and nutrition during early life, which is relevant to developmental programming of NAFLD. [ABSTRACT FROM AUTHOR]

Relationships of growth, metabolism, reproduction, and body size to the biological process of aging and longevity have been studied for decades and various unifying "theories of aging" have been proposed to account for the observed associations. In general, fast development, early sexual maturation leading to early reproductive effort, as well as production of many offspring, have been linked to shorter lifespans. The relationship of adult body size to longevity includes a remarkable contrast between the positive correlation in comparisons between different species and the negative correlation seen in comparisons of individuals within the same species. We now propose that longevity and presumably also the rate of aging are related to the "pace-of-life." A slow pace-of-life including slow growth, late sexual maturation, and a small number of offspring, predicts slow aging and long life. The fast pace of life (rapid growth, early sexual maturation, and major reproductive effort) is associated with faster aging and shorter life, presumably due to underlying trade-offs. The proposed relationships between the pace-of-life and longevity apply to both inter- and intra-species comparisons as well as to dietary, genetic, and pharmacological interventions that extend life and to evidence for early life programming of the trajectory of aging. Although available evidence suggests the causality of at least some of these associations, much further work will be needed to verify this interpretation and to identify mechanisms that are responsible. [ABSTRACT FROM AUTHOR]

Early-life environmental exposures influence long-lasting immune phenotypes and disease susceptibility. Immunity comprises durable programmable components that are affected by early environmental interactions and maintained in a stable manner. Some immune components are intrinsically programmable, whereas others are influenced by critical developmental processes during early life. Non-immune factors, including microbiota, hormones, and metabolites, strongly impact immune programming. Developmental immune programming may promote adaptation to anticipated future environments, but mismatches between predicted and actual environments can lead to disease. We propose that developmental programming of the immune system is possible due to programmable components of immunity. These developmentally programmable components are established by their interaction with an early-life environment and result in persistent immune alterations and disease susceptibility. Early-life environmental exposures play a significant role in shaping long-lasting immune phenotypes and disease susceptibility. Nevertheless, comprehensive understanding of the developmental programming of immunity is limited. We propose that the vertebrate immune system contains durable programmable components established through early environmental interactions and maintained in a stable and homeostatic manner. Some immune components, such as immunological memory, are intrinsically programmable. Others are influenced by conditions during critical developmental windows in early life, including microbiota, hormones, metabolites, and environmental stress, which impact programming. Developmental immune programming can promote adaptation to an anticipated future environment. However, mismatches between predicted and actual environments can result in disease. This is relevant because understanding programming mechanisms can offer insights into the origin of inflammatory diseases, ideally enabling effective prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

Fetuses with intrauterine growth restriction (FGR) have impaired oxidative and energy metabolism, with persistent consequences on their postnatal development. In this study, we test the hypothesis that FGR skeletal muscle has lower mitochondrial respiration rate and alters the transcriptomic profiles associated with energy metabolism in an ovine model. At late gestation, mitochondrial oxygen consumption rates (OCRs) and transcriptome profiles were evaluated in the skeletal muscle collected from FGR and control fetuses. The ex vivo mitochondrial OCRs were reduced (p < 0.01) in permeabilized FGR soleus muscle compared to the control muscle but only with pyruvate as the metabolic substrate. Mitochondrial OCRs were similar between the FGR and control groups for palmitoyl-carnitine (fatty acid-driven) or pyruvate plus palmitoyl-carnitine metabolic substrates. A total of 2284 genes were differentially expressed in the semitendinosus muscle from growth restricted fetuses (false discovery rate (FDR) ≤ 0.05). A pathway analysis showed that the upregulated genes (FGR compared to control) were overrepresented for autophagy, HIF-1, AMPK, and FOXO signaling pathways (all with an FDR < 0.05). In addition, the expression of genes modulating pyruvate's entry into the TCA cycle was downregulated, whereas the genes encoding key fatty acid oxidation enzymes were upregulated in the FGR muscle. These findings show that FGR skeletal muscle had attenuated mitochondrial pyruvate oxidation, possibly associated with the inability of pyruvate to enter into the TCA cycle, and that fatty acid oxidation might compensate for the attenuated energy metabolism. The current study provided phenotypic and molecular evidence for adaptive deficiencies in FGR skeletal muscle. [ABSTRACT FROM AUTHOR]

Advanced age at conception usually refers to human mothers aged 35 years plus and fathers aged 40 years plus. Advanced parental age may be responsible for genetic and/or epigenetic alterations and may affect the health of offspring. Limited epidemiological and experimental studies have addressed the effect of advanced parental age on cardio‐metabolic functions in human and rodent offspring. This mini review aimed to present the knowledge by focusing on adverse and favourable outcomes related to sex‐specific risks and intergenerational inheritance. The outcomes identified by this review were mainly negative, but there were also some positive results. [ABSTRACT FROM AUTHOR]

Multiparous dams have been reported to produce offspring with greater fertility and higher AMH concentration, as a marker of ovarian reserves, as compared with nulliparous and primiparous dams. Yet it has remained to be addressed whether this phenomenon can still be true for old multiparous cows which might experience some geriatric changes in their reproductive system. Therefore, the present study was conducted to evaluate the productive and reproductive performance of offspring with different maternal parity. To this end, offspring were classified based on their maternal parities into four categories, including offspring of nulliparous (no previous parity), primiparous (one previous parity), young multiparous (two to six previous parities) and old multiparous (seven or more previous parities) dams. In study I, data of birth weight, milk yield and reproductive variables of 11,788 offspring and data of their maternal parity were retrieved. In study II, blood samples (n = 521) were collected from offspring with various maternal parity for measurement of serum AMH. Birth weight was the lowest in the offspring of nulliparous dams (P < 0.0001) and it was lower in offspring of primiparous and old multiparous dams than offspring of young multiparous dams (P < 0.05). Milk production was the lowest in offspring of old multiparous dams (P < 0.01), and it was lower in offspring of young multiparous dams than offspring of nulliparous and primiparous dams (P < 0.0001). Offspring of old multiparous dams had greater first service conception rate, less services per conception and shorter calving to conception interval than offspring of nulliparous, primiparous and young multiparous dams (P < 0.05). Furthermore, AMH concentration was higher in offspring of old multiparous dams than offspring of nulliparous and primiparous dams (P < 0.05). In conclusion, the present study revealed greater milk production in offspring resulting from dams with lower parity, probably due to the genetic selection for improvement of milk production in dairy cows which imparts the younger generations greater genetic merits for milk production. Reproductive performance, however, was greater in offspring born to dams with higher parity, particularly those born to old multiparous dams, and this phenomenon might be related to their lower milk production and higher AMH concentration. • Nulliparous dams produced the lightest calves. • Milk yield was the highest in offspring born to nulliparous and primiparous dams. • Offspring born to old multiparous dams had the highest concentration of AMH. • Offspring born to old multiparous dams had the greatest reproductive performance. [ABSTRACT FROM AUTHOR]

The conditions animals experience during the early developmental stages of their lives can have critical ongoing effects on their future health, welfare, and proper development. In this paper we draw on evolutionary theory to improve our understanding of the processes of developmental programming, particularly Predictive Adaptive Responses (PAR) that serve to match offspring phenotype with predicted future environmental conditions. When these predictions fail, a mismatch occurs between offspring phenotype and the environment, which can have long-lasting health and welfare effects. Examples include metabolic diseases resulting from maternal nutrition and behavioral changes from maternal stress. An understanding of these processes and their evolutionary origins will help in identifying and providing appropriate developmental conditions to optimize offspring welfare. This serves as an example of the benefits of using evolutionary thinking within veterinary science and we suggest that in the same way that evolutionary medicine has helped our understanding of human health, the implementation of evolutionary veterinary science (EvoVetSci) could be a useful way forward for research in animal health and welfare. [ABSTRACT FROM AUTHOR]

The number of pregnancies complicated by obesity is increasing in line with the worldwide obesity crisis; recent estimates suggest that in developed countries more than 50% of pregnancies are in women who are overweight or have obesity. Maternal obesity is associated with an increased risk of many adverse outcomes for both the mother and baby during pregnancy and birth. In addition to these immediate outcomes, maternal obesity before and during pregnancy is associated with an increased risk of offspring cardio-metabolic disease later in life. Studies comparing siblings discordant for in utero exposure to maternal obesity suggest this is not simply due to transmission of 'obesogenic genes' between mother and child or current lifestyle factors, but reflects a direct impact of the obese intrauterine environment on fetal development. This review will describe the long-term consequences of exposure to maternal obesity during development for the cardio-metabolic health of the offspring. It will also discuss the potential molecular mechanisms that underlie the increased risk of metabolic disease in offspring of mothers with obesity, and explore interventions that may be implemented during pregnancy to limit the impact of obesity on offspring long-term health. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part I)'. [ABSTRACT FROM AUTHOR]

Maternal obesity programs the offspring to metabolic dysfunction. However, the effects of maternal obesity on skeletal muscle programming and ageing have been little explored. To determine if maternal obesity is a detriment to the progress of age-related muscle strength loss in the offspring (F1), we evaluated the indicators of muscle strength, adiposity, and metabolism at young adult and senior adult ages of maternal obesity F1 (MOF1) males and females from a high-fat diet-induced maternal obesity model in rat. Controls were age-matched siblings whose mothers were fed a standard maternal diet (CF1). Combinatorial data analysis was performed with body weight (BW), forelimb grip strength (FGS), FGS adjusted with BW, body fat, adiposity index, and serum triacylglycerols, cholesterol, glucose, insulin, and homeostatic model assessment for insulin resistance variables, to identify discriminant traits of variation among F1 groups. During ageing, maternal obesity caused glucose and cholesterol metabolic dysfunctions in male F1, whereas adiposity-associated skeletal strength loss and fatty acid alterations were present in female offspring. In conclusion, offspring programming–ageing effects due to maternal obesity impact metabolism and skeletal muscle strength loss at later ages in a sex-dependent manner. [ABSTRACT FROM AUTHOR]

Fall-calving Hereford-SimAngus heifers [single-sired; body weight (BW): 451 ± 28 (SD) kg; body condition score (BCS): 5.4 ± 0.7] bred to a single sire were individually-fed 100% (control; CON; n = 12) or 70% (nutrient restricted; NR; n = 13) of estimated metabolizable energy and metabolizable protein requirements for maintenance, pregnancy, and growth from d 160 of gestation to calving. Post-calving, all females were fed to meet lactational nutrient requirements until weaning. From d 1 to 147 of lactation, dams were individually fed chopped tall fescue hay and supplemented in Calan gates to constrain diets of calves to milk only. After d 147, dams and calves were managed as a group in drylots, and calves could access the tall fescue hay offered to their dams. Bull calves (CON; n = 8; NR; n = 9) were castrated at 176 ± 3 (SD) d of age to represent a later pre-pubertal growth stage that is indicative of post-pubertal testis size. The epididymis and pampiniform plexus were removed, and calipers were used to determine the length and perpendicular widths of each testis. Testis weight was recorded, and testis volume was determined by water displacement in a graduated cylinder. Testis parenchyma was fixed in neutral buffered formalin for histological analyses. Seminiferous tubule diameter was measured on perpendicular diameters of 40 randomly chosen tubules with a visibly round cross-section. Data were analyzed with late gestational nutritional plane and calving date as fixed effects. Birth weight of bull calves was not affected (P > 0.99), but we previously reported that late gestational nutrient restriction decreased (P ≤ 0.04) milk production by 15% during the first 147 d of lactation. By d 63 of age, bull calves born to previously NR dams weighed less (P = 0.03) than bull calves born to CON dams. Body weight remained different (P ≤ 0.04) until castration, at which point bull calves born to previously NR dams weighed 14% less (P = 0.02) than bull calves born to CON dams. Average testis diameter was less (P = 0.03), and average testis length tended to be less (P = 0.07) for calves born to previously NR dams. Paired testes weight and volume were less (P ≤ 0.05) for calves born to previously NR dams, but testes weight relative to calf BW and average seminiferous tubule diameter were not affected (P ≥ 0.20) by late gestational nutritional plane. In the current study, pre-pubertal bull calves born to NR dams had decreased testis size, but it is difficult to delineate if this is a direct effect of gestational undernutrition on fetal development or its indirect effect on post-weaning development due to decreased milk production. [ABSTRACT FROM AUTHOR]

Simple Summary: The prenatal environment can influence the postnatal performance of cattle. Especially in tropical regions, pregnant beef cows may experience nutritional restriction during gestation, which coincides with the season of poor quality and quantity of feed. Thus, it was verified that the offspring of cows subjected to a better gestation environment exhibited better productive and reproductive performances throughout their lives. In terms of genetic merit, it was found that the best animals in a restricted gestational environment are not necessarily the same in a favorable gestational environment. In other words, for each condition of the gestational environment, there are animals specifically suited to perform better. In addition, regions in the genome of these animals responsible for several traits of economic importance in cattle were identified. Thus, for a more efficient selection process, breeders must consider the effect of genotype by prenatal environment interaction and provide adequate management and nutrition care for pregnant cows. The prenatal environment is recognized as crucial for the postnatal performance in cattle. In tropical regions, pregnant beef cows commonly experience nutritional restriction during the second half of the gestation period. Thus, the present study was designed to analyze the genotype by prenatal environment interaction (G × Epn) and to identify genomic regions associated with the level and response in growth and reproduction-related traits of beef cattle to changes in the prenatal environment. A reaction norm model was applied to data from two Nelore herds using the solutions of contemporary groups for birth weight as a descriptor variable of the gestational environment quality. A better gestational environment favored weights until weaning, scrotal circumference at yearling, and days to first calving of the offspring. The G × Epn was strong enough to result in heterogeneity of variance components and genetic parameters in addition to reranking of estimated breeding values and SNPs effects. Several genomic regions associated with the level of performance and specific responses of the animals to variations in the gestational environment were revealed, which harbor QTLs and can be exploited for selection purposes. Therefore, genetic evaluation models considering G × Epn and special management and nutrition care for pregnant cows are recommended. [ABSTRACT FROM AUTHOR]

Individuals born preterm are at higher risk of cardiovascular and metabolic diseases in adulthood, through mechanisms not completely understood. White adipose tissue in humans and rodents is a dynamic endocrine organ and a critical player in the regulation of metabolic homeostasis. However, the impact of preterm birth on white adipose tissue remains unknown. Using a well‐established rodent model of preterm birth‐related conditions in which newborn rats are exposed during postnatal days 3–10 to 80% of oxygen, we evaluated the impact of transient neonatal hyperoxia on adult perirenal white adipose tissue (pWAT) and liver. We further assessed the effect of a second hit with a high‐fat high‐fructose hypercaloric diet (HFFD). We evaluated 4‐month‐old adult male rats after 2 months of HFFD. Neonatal hyperoxia led to pWAT fibrosis and macrophage infiltration without modification in body weight, pWAT weight, or adipocyte size. In animals exposed to neonatal hyperoxia vs. room air control, HFFD resulted in adipocyte hypertrophy, lipid accumulation in the liver, and increased circulating triglycerides. Overall, preterm birth‐related conditions had long‐lasting effects on the composition and morphology of pWAT, along with a higher susceptibility to the deleterious impact of a hypercaloric diet. These changes suggest a developmental pathway to long‐term metabolic risk factors observed clinically in adults born preterm through programming of white adipose tissue. [ABSTRACT FROM AUTHOR]

Individuals born after intrauterine growth restriction (IUGR) are at risk of developing cardiovascular diseases (CVDs). Endothelial dysfunction plays a role in the pathogenesis of CVDs; and endothelial colony-forming cells (ECFCs) have been identified as key factors in endothelial repair. In a rat model of IUGR induced by a maternal low-protein diet, we observed an altered functionality of ECFCs in 6-month-old males, which was associated with arterial hypertension related to oxidative stress and stress-induced premature senescence (SIPS). Resveratrol (R), a polyphenol compound, was found to improve cardiovascular function. In this study, we investigated whether resveratrol could reverse ECFC dysfunctions in the IUGR group. ECFCs were isolated from IUGR and control (CTRL) males and were treated with R (1 μM) or dimethylsulfoxide (DMSO) for 48 h. In the IUGR-ECFCs, R increased proliferation (5′-bromo-2′-deoxyuridine (BrdU) incorporation, p < 0.001) and improved capillary-like outgrowth sprout formation (in Matrigel), nitric oxide (NO) production (fluorescent dye, p < 0.01), and endothelial nitric oxide synthase (eNOS) expression (immunofluorescence, p < 0.001). In addition, R decreased oxidative stress with reduced superoxide anion production (fluorescent dye, p < 0.001); increased Cu/Zn superoxide dismutase expression (Western blot, p < 0.05); and reversed SIPS with decreased beta-galactosidase activity (p < 0.001), and decreased p16ink4a (p < 0.05) and increased Sirtuin-1 (p < 0.05) expressions (Western blot). No effects of R were observed in the CTRL-ECFCs. These results suggest that R reverses long-term ECFC dysfunctions related to IUGR. [ABSTRACT FROM AUTHOR]

Mast cells (MCs) are evolutionarily ancient innate immune cells with important roles in protective immunity against bacteria, parasites, and venomous animals. They can be found in most organs of the body, where they also contribute to normal tissue functioning, for example by engaging in crosstalk with nerves. Despite this, they are most widely known for their detrimental roles in allergy, anaphylaxis, and atopic disease. Just like macrophages, mast cells were conventionally thought to originate from the bone marrow. However, they are already present in fetal tissues before the onset of bone marrow hematopoiesis, questioning this dogma. In recent years, our view of myeloid cell ontogeny has been revised. We now know that the first mast cells originate from progenitors made in the extra-embryonic yolk sac, and later get supplemented with mast cells produced from subsequent waves of hematopoiesis. In most connective tissues, sizeable populations of fetal-derived mast cells persist into adulthood, where they self-maintain largely independently from the bone marrow. These developmental origins are highly reminiscent of macrophages, which are known to have critical functions in development. Mast cells too may thus support healthy development. Their fetal origins and longevity also make mast cells susceptible to genetic and environmental perturbations, which may render them pathological. Here, we review our current understanding of mast cell biology from a developmental perspective. We first summarize how mast cell populations are established from distinct hematopoietic progenitor waves, and how they are subsequently maintained throughout life. We then discuss what functions mast cells may normally have at early life stages, and how they may be co-opted to cause, worsen, or increase susceptibility to disease. [ABSTRACT FROM AUTHOR]

Melatonin, an endogenous hormone mainly released at night by the pineal gland, has multifaceted biofunctions. Emerging evidence points to melatonin having a crucial role in kidney health and disease. As the prevalence of chronic kidney disease (CKD) is still rising, a superior strategy to advance global kidney health is needed to not just treat CKD, but prevent it early on. Adult kidney disease can have its origins in early life. This review aims to evaluate the recent literature regarding melatonin's effect on kidney development, its clinical uses in the early stage of life, animal models documenting preventive applications of melatonin on offspring's kidney-related disease, and a thorough summary of therapeutic considerations concerning melatonin supplementation. [ABSTRACT FROM AUTHOR]

Although the effect of mastitis on reproduction and production of lactating dairy cows has been vastly studied, little information is available about the association of maternal udder health status with offspring reproduction and production. Therefore, the present research was conducted to study the association between maternal average monthly somatic cell count (SCC) with reproduction, anti-Müllerian hormone (AMH) concentration, udder health status and milk production in the offspring. Based on maternal average monthly SCC (MSCC), offspring were classified into five categories including MSCC1 (SCC <200,000; n = 3005), MSCC2 (200,000 ≤ SCC <400,000; n = 252), MSCC3 (400,000 ≤ SCC <600,000; n = 103), MSCC4 (600,000 ≤ SCC <800,000; n = 40) and MSCC5 (SCC ≥800,000; n = 61). Data associated with reproduction, production and udder health status of offspring were retrieved from the herd database. In addition, blood samples were collected from a subset of offspring (n = 136) for measurement of serum AMH, as a reliable marker of ovarian reserves. Offspring in MSCC5 category had more services per conception and longer calving to conception interval than offspring in MSCC1 and MSCC2 categories (P < 0.05). The average number of SCC and risk of clinical mastitis in the offspring were not associated with MSCC (P > 0.05). But offspring in MSCC5 category produced less milk, fat and protein than offspring in MSCC1 category (P < 0.05). In addition, AMH concentration was lower in MSCC5 than MSCC1 category (P < 0.05). In conclusion, the present study showed that elevated maternal average monthly SCC could culminate in birth of offspring with inferior reproductive performance, smaller size of ovarian reserves and lower level of milk production during the first lactation period. • Offspring born to dams with an average monthly SCC ≥800,000 had more services per conception and longer calving to conception interval. • Offspring born to dams with an average monthly SCC ≥800,000 produced lower milk, fat and protein. • Offspring born to dams with an average monthly SCC ≥800,000 had lower con centration of AMH. [ABSTRACT FROM AUTHOR]

Maternal diet and obesity (MO) may influence taste preferences and increase the susceptibility to obesity in offspring, but the impact of MO per se to these influences is poorly understood. We evaluated the influence of MO on food choice and susceptibility to obesity in offspring when mothers consumed a standard diet (SD). Mice with the Lethal yellow mutation (Ay/a) develop obesity consuming an SD. Metabolic parameters were assessed in pregnant and lactating Ay/a (obesity) and a/a (control) mothers. Metabolic response to the consumption of a sweet–fat diet (SFD: SD, lard, and sweet biscuits) and the choice of components of this diet were evaluated in their male and female offspring. Compared to control mothers, pregnant obese mothers had higher levels of insulin, leptin, and FGF21. MO increased food intake and liver expression of lipogenesis genes in male offspring consuming the SD. SFD consumption caused obesity development and insulin resistance, increased liver expression of glycolytic and lipogenesis genes, and affected hypothalamic expression of anorexigenic and orexigenic genes. In offspring of both sexes, MO had no effect on food choice and metabolic response to SFD intake. Therefore, when obese mothers consume a balanced diet, MO does not affect food choice and development of diet-induced obesity in offspring. [ABSTRACT FROM AUTHOR]

Understanding the consequences of heat exposure on mitochondrial function is crucial as mitochondria lie at the core of metabolic processes, also affecting population dynamics. In adults, mitochondrial metabolism varies with temperature but can also depend on thermal conditions experienced during development. We exposed zebra finches to two alternative heat treatments during early development: "constant", maintained birds at ambient 35 °C from parental pair formation to fledglings' independence, while "periodic" heated broods at 40 °C, 6 h daily at nestling stage. Two years later, we acclimated birds from both experiments at 25 °C for 21 days, before exposing them to artificial heat (40 °C, 5 h daily for 10 days). After both conditions, we measured red blood cells' mitochondrial metabolism using a high-resolution respirometer. We found significantly decreased mitochondrial metabolism for Routine, Oxidative Phosphorylation (OxPhos) and Electron Transport System maximum capacity (ETS) after the heat treatments. In addition, the birds exposed to "constant" heat in early life showed lower oxygen consumption at the Proton Leak (Leak) stage after the heat treatment as adults. Females showed higher mitochondrial respiration for Routine, ETS and Leak independent of the treatments, while this pattern was reversed for OxPhos coupling efficiency (OxCE). Our results show that short-term acclimation involved reduced mitochondrial respiration, and that the reaction of adult birds to heat depends on the intensity, pattern and duration of temperature conditions experienced at early-life stages. Our study provides insight into the complexity underlying variation in mitochondrial metabolism and raises questions on the adaptive value of long-lasting physiological adjustments triggered by the early-life thermal environment. [ABSTRACT FROM AUTHOR]

There is growing evidence that poor paternal diet at the time of conception increase the risk of offspring developing a range of non-communicable metabolic diseases, such as obesity, diabetes and cardiovascular disease, in adulthood. We hypothesise that a paternal low protein–high carbohydrate diet perturbs offspring tissue lipid abundance through both sperm and seminal plasma-mediated mechanisms. To test our hypothesis, we fed male C57BL/6 mice either a control normal protein diet (NPD; 18% protein) or an isocaloric low protein diet (LPD; 9% protein) for a minimum of 8 weeks. We generated offspring through artificial insemination, in combination with vasectomised male mating. Using this approach, we derived offspring from either NPD or LPD sperm but in the presence of NPD or LPD seminal plasma. Using high resolution mass-spectrometry, we found that offspring derived from either LPD sperm or seminal fluid displayed perturbed cardiac and brain lipid abundance from just three weeks of age, typically associated with the altered abundance of tissue triglycerides. We also observed the differential sex-specific patterns of lipids between the control and experimental offspring's hearts and brains. These observations indicate that poor paternal diet at the time of conception affects offspring cardiac and brain lipid profiles in an age-, sex- and generation-specific manner. [ABSTRACT FROM AUTHOR]

Podocytes are terminally differentiated epithelial cells in glomeruli. Podocyte injury and loss are features of many diseases leading to chronic kidney disease (CKD). The developmental origins of health and disease hypothesis propose an adverse intrauterine environment can lead to CKD later in life, especially when a second postnatal challenge is experienced. The aim of this study was to examine whether a suboptimal maternal environment would result in reduced podocyte endowment, increasing susceptibility to diabetes‐induced renal injury. Female C57BL/6 mice were fed a low protein diet (LPD) to induce growth restriction or a normal protein diet (NPD) from 3 weeks before mating until weaning (postnatal Day 21, P21) when nephron and podocyte endowment were assessed in one male and one female offspring per litter. Littermates were administered streptozotocin or vehicle at 6 weeks of age. Urinary albumin excretion, glomerular size, and podometrics were assessed following 18 weeks of hyperglycemia. LPD offspring were growth restricted and had lower nephron and podocyte number at P21. However, by 24 weeks the podocyte deficit was no longer evident and despite low nephron endowment neither albuminuria nor glomerulosclerosis were observed. Podocyte number was unaffected by 18 weeks of hyperglycemia in NPD and LPD offspring. Diabetes increased glomerular volume reducing podocyte density, with more pronounced effects in LPD offspring. LPD and NPD diabetic offspring developed mild albuminuria with LPD demonstrating an earlier onset. LPD offspring also developed glomerular pathology. These findings indicate that growth‐restricted LPD offspring with low nephron number and normalized podocyte endowment were more susceptible to alterations in glomerular volume and podocyte density leading to more rapid onset of albuminuria and renal injury than NPD offspring. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) exposure in adulthood is associated with nonalcoholic fatty liver disease (NAFLD), characterized by steatosis, inflammation, and fibrosis. The prevalence of NAFLD in children is increasing, suggesting a role for the developmental environment in programming susceptibility. However, the role of developmental Cd exposure in programming NAFLD and the underlying mechanisms remain unclear. We have proposed that imprinted genes are strong candidates for connecting the early life environment and later life disease. In support of this, we previously identified roles for the Imprinted Gene Network (IGN) and its regulator Zac1 in programming NAFLD in response to maternal metabolic dysfunction. Here, we test the hypothesis that developmental Cd exposure is sufficient to program NAFLD, and further, that this process is mediated by Zac1 and the IGN. Using mice, we show that developmental cadmium chloride (CdCl2) exposure leads to histological, biochemical, and molecular signatures of steatosis and fibrosis in juveniles. Transcriptomic analyses comparing livers of CdCl2-exposed and control mice show upregulation of Zac1 and the IGN coincident with disease presentation. Increased hepatic Zac1 expression is independent of promoter methylation and imprinting statuses. Finally, we show that over-expression of Zac1 in cultured hepatocytes is sufficient to induce lipid accumulation in a Ppar γ -dependent manner and demonstrate direct binding of Zac1 to the Pparγ promoter. Our findings demonstrate that developmental Cd exposure is sufficient to program NAFLD in later life, and with our previous work, establish Zac1 and the IGN as key regulators of prosteatotic and profibrotic pathways, two of the major pathological hallmarks of NAFLD. [ABSTRACT FROM AUTHOR]

Fall-calving primiparous beef females [body weight: 451 ± 28 (SD) kg; body condition score: 5.4 ± 0.7] were individually-fed either 100% (control; CON; n = 13) or 70% (nutrient restricted; NR; n = 13) of metabolizable energy and metabolizable protein requirements for maintenance, pregnancy, and growth from day 160 of gestation to parturition. Calves were reared naturally by their dams and monitored for latency times from birth to first sternal recumbency, attempt to stand, and stand; vigor scores were assigned at 2, 5, 10, and 20 min of age. Rectal temperatures and jugular blood were obtained at 0 (pre-suckling), 6, 12, 24, and 48 h of age, and blood chemistry, hematology, cortisol, and insulin were determined. Data were analyzed with fixed effects of late gestational nutritional plane (single data point) or nutritional plane, hour, and their interaction (data over time, repeated measures). Calving date was a fixed effect; calf sex was included when P < 0.25. We previously reported that late gestational nutritional plane did not affect gestation length or calf size at birth, but calving assistance and fetal malpresentation occurred more often in NR. Nutritional plane did not affect (P = 0.65) duration of parturition, but calves born to NR dams had slower times to attempt to stand (P = 0.09), slower times to stand (P = 0.02), and poorer 20 min vigor scores (P = 0.05). Serum immunoglobulin G and A concentrations at 48 h were greater (P ≤ 0.03) for NR calves. Rectal temperature of NR calves was less (P = 0.02) at 0 h, but greater (P = 0.04) at 24 h compared with CON. Circulating glucose, non-esterified fatty acids, triglycerides, cortisol, and insulin were not affected by nutritional plane (P ≥ 0.18). Total protein and globulin from 6 to 48 h were greater (P ≤ 0.02) in NR calves. Calves from NR dams had greater (P ≤ 0.08) gamma-glutamyl transferase at 6, 12, and 48 h. Serum aspartate aminotransferase was greater (P ≤ 0.07) from 0 to 24 h and creatine kinase was greater (P ≤ 0.04) from 6 to 24 h in NR calves. At 0 h, potassium was greater (P = 0.03) in NR calves. Calves born to CON had greater chloride (P = 0.08; main effect), sodium (P ≤ 0.09) from 0 to 48 h, and anion gap (P = 0.02) at 6 h. Hematocrit from 6 to 24 h and red blood cells and hemoglobin at 6 and 12 h were greater (P ≤ 0.09) in CON calves. These data indicate that nutrient restriction during late gestation resulted in less vigorous calves with more indicators of trauma in early life. [ABSTRACT FROM AUTHOR]

Fall-calving primiparous crossbred beef females [body weight (BW): 451 ± 28 (SD) kg; body condition score (BCS): 5.4 ± 0.7] were allocated by fetal sex and expected calving date to receive either 100% (control; CON; n = 13) or 70% (nutrient restricted; NR; n = 13) of metabolizable energy and metabolizable protein requirements for maintenance, pregnancy, and growth from day 160 of gestation to calving. Heifers were individually-fed chopped poor quality hay and supplemented to meet targeted nutritional planes based on estimated hay intakes. Dam BW, BCS, backfat, and metabolic status were determined pre-treatment, every 21 d (BW and metabolic status) or 42 d (BCS and backfat) during gestation, and post-calving. At birth, calf BW and size were measured, and total colostrum from the most full rear quarter was collected pre-suckling. Data were analyzed with nutritional plane, treatment initiation date, and calf sex (when P < 0.25) as fixed effects. Gestational metabolites included day and nutritional plane × day as repeated measures. During late gestation, CON dams gained (P < 0.01) maternal (non-gravid) BW and maintained (P ≥ 0.17) BCS and backfat, while NR dams lost (P < 0.01) maternal BW, BCS, and backfat. Circulating glucose, urea N, and triglycerides were less (P ≤ 0.05) in NR dams than CON at most late gestational timepoints after treatment initiation. Circulating non-esterified fatty acids were greater (P < 0.01) in NR dams than CON. Post-calving, NR dams weighed 63.6 kg less (P < 0.01) and were 2.0 BCS less (P < 0.01) than CON. At 1 h post-calving, NR dams had less (P = 0.01) plasma glucose and tended to have less (P = 0.08) plasma triglycerides than CON. Nutrient restriction did not affect (P ≥ 0.27) gestation length, calf birth weight, or calf size at birth. Colostrum yield was 40% less (P = 0.04) in NR dams than CON. Protein and immunoglobulin concentrations were greater (P ≤ 0.04), but free glucose and urea N concentrations were less (P ≤ 0.03), in colostrum of NR dams than CON. Colostrum total lactose, free glucose, and urea N were less (P ≤ 0.03) in NR dams than CON, but total protein, triglycerides, and immunoglobulins were not affected (P ≥ 0.55). In summary, beef heifers experiencing late gestational nutrient restriction prioritized partitioning nutrients to fetal growth and colostrum production over maternal growth. During undernutrition, fetal and colostral nutrient demands were largely compensated for by catabolism of maternal tissue stores. [ABSTRACT FROM AUTHOR]

Feeding rumen-protected choline (RPC) to late gestation dairy cows has potential to affect growth in offspring. The objective of this study was to evaluate the effects of in utero choline exposure on the growth, feed efficiency (FE), metabolism, and carcass quality of Angus × Holstein cattle. Multiparous Holstein cows pregnant with male (N = 17) or female (N = 30) Angus-sired calves were enrolled 21 d prepartum and randomly assigned to one of four dietary treatments varying in quantity and formulation of RPC. The treatments included a control with 0 g/d supplemental RPC (CTL), supplemental RPC fed at the recommended dose (RD) of 15 g/d from either an established RPC product (RPC1RD; ReaShure; Balchem Corp.) or choline ion from a concentrated RPC prototype (RPC2RD; Balchem Corp.), or a high dose (HD) of RPC2 fed at 22 g/d (RPC2HD). From 2 to 6 mo of age, calves were group housed and offered 2.3 kg grain/hd/d (42% CP) with ad libitum grass hay, and stepped up to a complete finishing diet by 7 mo (12.0% CP; 1.34 Mcal/kg NEg). Weight and height were measured monthly. Animal FE was measured in individual pens for 35 d at 8 mo. Feed intake was measured daily, and blood was obtained on day 18 during the FE period. Afterwards, cattle were group housed and offered a free-choice finishing diet until slaughter, where carcass yield and quality characteristics were measured. Mixed models were used in PROC MIXED (SAS, 9.4) with the fixed effects of treatment, sex, time, their interactions, and the random effect of calf. Month was the repeated measure, and preplanned contrasts were used. Blood and FE data were analyzed with the fixed effect of dam choline treatment, calf sex, and the interaction. Increasing dose of RPC tended to increase weight over the entire study period. Feeding any RPC increased hip and wither height compared with CTL, and increasing RPC dose linearly increased hip and wither height. Treatment and sex interacted on DMI whereby increasing RPC intake linearly increased DMI for males but not females. Compared with control, feeding any RPC decreased plasma insulin, glucose, and an insulin sensitivity index (RQUICKI). In utero choline exposure increased kidney–pelvic–heart fat and marbling score. Mechanisms of action for intrauterine choline exposure on offspring growth, metabolism, and carcass characteristics should be explored as they have direct implications for profitability for cattle growers and feeders. [ABSTRACT FROM AUTHOR]

To determine effects of dam parity on perinatal nutrient availability in beef cattle, data and samples were collected from 18 primiparous and 35 multiparous spring-calving Sim-Angus dams and their calves. Time to stand was recorded and neonatal vigor assessed. Jugular blood was collected from a subset of calves at 0 (post-standing and pre-suckling) 6, 12, 24, 48, and 72 h of age, and blood chemistry panels were completed. Expelled placentas were dissected, dried, and weighed. Prepartum maternal circulating glucose, non-esterified fatty acids (NEFA), triglycerides, and urea N were analyzed. All statistical models included the fixed effect of dam parity, and calf sex (when P ≤ 0.25) was included for calf and placental variables. Effects of sampling hour, and parity × hour were included for calf metabolites over time using repeated measures. Multiparous dams had greater body weight prepartum (P < 0.001) but similar (P = 0.25) body condition score. Maternal circulating urea N and triglycerides were greater (P ≤ 0.05) in multiparous dams pre-calving. Calves born to primiparous dams weighed 10% less (P ≤ 0.04) at birth with smaller (P ≤ 0.01) heart and abdominal girths. Cotyledonary, intercotyledonary, and total placental masses were less (P ≤ 0.05) for primiparous dams. Dam parity did not affect (P ≥ 0.58) calf time to stand, vigor score at 10 min, or rectal temperature. Serum glucose was greater (P = 0.03) at 0 h but less (P ≤ 0.04) at all other hours in calves from primiparous dams. Calves from primiparous dams had greater (P ≤ 0.02) serum NEFA at 6, 12, and 24 h although plasma triglycerides were greater (P < 0.001) at 6 h. Calves from primiparous dams had greater (P ≤ 0.04) serum urea N at 12 h and creatinine at 12 and 24 h. Plasma insulin was greater (P ≤ 0.04) in calves from multiparous dams at 12, 48, and 72 h, but parity did not affect (P ≥ 0.18) serum total protein or plasma cortisol. Serum aspartate aminotransferase was greater (P ≤ 0.04) at 6 and 24 h, creatine kinase was greater at 24 h, and gamma-glutamyl transpeptidase was less (P ≤ 0.04) at 6, 12, and 24 h, for calves from primiparous dams. Calves born to primiparous dams had greater (P ≤ 0.02) total bilirubin and direct bilirubin at 12 and 24 h. Data indicate that calves born to first-parity heifers had decreased perinatal nutrient availability, resulting in reduced fetal and placental growth, as well as greater energy reserve mobilization and metabolic indicators of stress as neonates. [ABSTRACT FROM AUTHOR]

Changes in the environment, including nutritional changes, can influence fetal and postnatal development of the offspring, which can result in differences in growth, metabolism, reproduction, and health later in life. In beef cattle research on energy and protein restriction during late gestation appears to be contradictory. Therefore, in this review, we will examine the nutrient requirements recommended for this period. We are summarizing contradictory data on effects on offspring performance with possible explanations of the reason for why the data seems contradictory. We will finish by discussing some areas that we consider important for further research to increase the knowledge on how maternal nutrition influences offspring development. In particular, suggestions are provided on the need for more accurately measuring nutrient and energy supply and use and the impact on subsequent epigenetic effects. This will improve understanding of nutritional effects during gestation on offspring performance. [ABSTRACT FROM AUTHOR]

Winter and spring precipitation are predicted to increase in the Midwest region of the United States, causing muddy conditions. In a previous experiment, Angus cows (8 per treatment) were paired based on initial body weight (BW) and one cow from each pair was randomly allocated to either the mud or control treatment. Though cows consumed the same amount of dry matter, cows in the mud treatment weighed 37.4 kg less than cows in the control treatment by day 269 of gestation. The objective of this experiment was to evaluate developmental programming effects of steers born to cows in the mud treatment (MUD; n = 7) or the control treatment (CON; n = 6). Steers were weighed at birth and then weekly from approximately 56 d of age until weaning and were subjected to a glucose tolerance test (GTT) and adrenocorticotropic hormone (ACTH) challenge after weaning. Steers were then placed in the feedlot for an 84-d growing phase and were weighed weekly and 12th rib back fat (BF) and ribeye area (REA) were imaged every 28 d using ultrasonography. Data were analyzed as a randomized complete block design with repeated measurements when appropriate (SAS 9.4). Although there was a 37.4 kg decrease in BW of cows by the end of gestation, there was no evidence of a pen treatment effect on calf birth weight (P = 0.60) or weaning weight (P = 0.99). Additionally, there was no evidence of a pen treatment × day effect for steer BW from birth to weaning (P = 0.67) or growing phase BW (P = 0.60). There was evidence of a treatment × day of growing phase effect (P = 0.02) for BF, such that CON steers had greater BF on day 28 of the growing phase; however, there was no evidence of a treatment × day effect for REA (P = 0.20). Furthermore, there was no evidence of a pen treatment effect for the growing phase average daily gain (P = 0.74), dry matter intake (P = 0.65), gain:feed (P = 0.48), plasma glucose concentration (P = 0.67) or plasma insulin concentration (P = 0.61) in response to the GTT, or plasma cortisol concentration in response to the ACTH challenge (P = 0.51). These results indicate that while mud increased net energy requirements for cows in the MUD treatment, there were no subsequent effects observed for steer BW, gain:feed, or response to glucose and ACTH during the growing phase. [ABSTRACT FROM AUTHOR]

Developmental programming is the concept that 'stressors' during development (i.e. pregnancy, the perinatal period and infancy) can cause long-term changes in gene expression, leading to altered organ structure and function. Such long-term changes are associated with an increased risk of a host of chronic pathologies, or non-communicable diseases including abnormal growth and body composition, behavioural or cognitive dysfunction, metabolic abnormalities, and cardiovascular, gastro-intestinal, immune, musculoskeletal and reproductive dysfunction. Maternal nutrition during the periconceptual period, pregnancy and postnatally can have profound influences on the developmental program. Animal models, including domestic livestock species, have been important for defining the mechanisms and consequences of developmental programming. One of the important observations is that maternal nutritional status and other maternal stressors (e.g. environmental temperature, high altitude, maternal age and breed, multiple fetuses, etc.) early in pregnancy and even periconceptually can affect not only embryonic/fetal development but also placental development. Indeed, altered placental function may underlie the effects of many maternal stressors on fetal growth and development. We suggest that future directions should focus on the consequences of developmental programming during the offspring's life course and for subsequent generations. Other important future directions include evaluating interventions, such as strategic dietary supplementation, and also determining how we can take advantage of the positive, adaptive aspects of developmental programming. Developmental programming, sometimes called fetal programming, is the concept that insults to the embryo/fetus during development can have long-term consequences throughout the lifetime of the offspring, including a host of chronic health problems. One of the most obvious and well-studied insults is poor maternal nutrition. This review discusses our current understanding of how developmental programming occurs, strategies to minimise its negative consequences (and, perhaps, take advantage of its positive consequences), as well as future directions for research. [ABSTRACT FROM AUTHOR]

The final weeks of gestation represent a critical period for dairy cows that can determine the success of the subsequent lactation. Many physiological changes take place and additional exogenous stressors can alter the success of the transition into lactation. Moreover, this phase is pivotal for the final stage of intrauterine development of the fetus, which can have negative long-lasting postnatal effects. Heat stress is widely recognised as a threat to dairy cattle welfare, health, and productivity. Specifically, late gestation heat stress impairs the dam's productivity by undermining mammary gland remodelling during the dry period and altering metabolic and immune responses in early lactation. Heat stress also affects placental development and function, with relevant consequences on fetal development and programming. In utero heat stressed newborns have reduced birth weight, growth, and compromised passive immune transfer. Moreover, the liver and mammary DNA of in utero heat stressed calves show a clear divergence in the pattern of methylation relative to that of in utero cooled calves. These alterations in gene regulation might result in depressed immune function, as well as altered thermoregulation, hepatic metabolism, and mammary development jeopardising their survival in the herd and productivity. Furthermore, late gestation heat stress appears to exert multigenerational effects, influencing milk yield and survival up to the third generation. As climate change continues at a rapid pace, more livestock will be subjected to heat stress for longer periods and absolute levels. In dairy cattle, heat stress profoundly impacts the subsequent productivity of late gestation cows and programs lower productivity and health in the offspring. This review considers the biological basis for the impact of heat stress on the dam and the daughter, and the epigenetic signals that result in the observed phenotypes. [ABSTRACT FROM AUTHOR]

Maternal obesity (MO) during pregnancy is linked to increased and premature risk of age‐related metabolic diseases in the offspring. However, the underlying molecular mechanisms still remain not fully understood. Using a well‐established nonhuman primate model of MO, we analyzed tissue biopsies and plasma samples obtained from post‐pubertal offspring (3–6.5 y) of MO mothers (n = 19) and from control animals born to mothers fed a standard diet (CON, n = 13). All offspring ate a healthy chow diet after weaning. Using untargeted gas chromatography‐mass spectrometry metabolomics analysis, we quantified a total of 351 liver, 316 skeletal muscle, and 423 plasma metabolites. We identified 58 metabolites significantly altered in the liver and 46 in the skeletal muscle of MO offspring, with 8 metabolites shared between both tissues. Several metabolites were changed in opposite directions in males and females in both liver and skeletal muscle. Several tissue‐specific and 4 shared metabolic pathways were identified from these dysregulated metabolites. Interestingly, none of the tissue‐specific metabolic changes were reflected in plasma. Overall, our study describes characteristic metabolic perturbations in the liver and skeletal muscle in MO offspring, indicating that metabolic programming in utero persists postnatally, and revealing potential novel mechanisms that may contribute to age‐related metabolic diseases later in life. [ABSTRACT FROM AUTHOR]

Teratological research shows that both prenatal stress and prenatal substance exposure have a significant impact on neurodevelopmental outcomes in children. Using human research, the purpose of this narrative review is to explore the degree to which these exposures may represent complex prenatal and postnatal risks for the development of cognition and behavior in children. An understanding of the HPA axis and its function during pregnancy as well as the types and operationalization of prenatal stress provide a context for understanding the direct and indirect mechanisms by which prenatal stress affects brain and behavior development. In turn, prenatal substance exposure studies are evaluated for their importance in understanding variables that indicate a potential interaction with prenatal stress including reactivity to novelty, arousal, and stress reactivity during early childhood. The similarities and differences between prenatal stress exposure and prenatal substance exposure on neurodevelopmental outcomes including arousal and emotion regulation, cognition, behavior, stress reactivity, and risk for psychopathology are summarized. Further considerations for teratological studies of prenatal stress and/or substance exposure include identifying and addressing methodological challenges, embracing the complexity of pre-and postnatal environments in the research, and the importance of incorporating parenting and resilience into future studies. • The challenges faced in teratological research on the effects of prenatal substances and stress exposures are reviewed. • Approaches to estimating the direct and indirect effects of prenatal substances and stress exposures are considered. • Similarities and differences in the effects of prenatal substances and stress effects on cognition and behavior are described. • The effects of prenatal substances and stress on emotion regulation, stress, and risk for psychopathology are compared. [ABSTRACT FROM AUTHOR]

Fructose consumption is now recognised as a major risk factor in the development of metabolic diseases, such as hyperlipidaemia, diabetes, non-alcoholic fatty liver disease and obesity. In addition to environmental, social, and genetic factors, an unfavourable intrauterine environment is now also recognised as an important factor in the progression of, or susceptibility to, metabolic disease during adulthood. Developmental trajectory in the short term, in response to nutrient restriction or excessive nutrient availability, may promote adaptation that serves to maintain organ functionality necessary for immediate survival and foetal development. Consequently, this may lead to decreased function of organ systems when presented with an unfavourable neonatal, adolescent and/or adult nutritional environment. These early events may exacerbate susceptibility to later-life disease since sub-optimal maternal nutrition increases the risk of non-communicable diseases (NCDs) in future generations. Earlier dietary interventions, implemented in pregnant mothers or those considering pregnancy, may have added benefit. Although, the mechanisms by which maternal diets high in fructose and the vertical transmission of maternal metabolic phenotype may lead to the predisposition to adult disease are poorly understood. In this review, we will discuss the potential contribution of excessive fructose intake during pregnancy and how this may lead to developmental reprogramming of mitochondrial function and predisposition to metabolic disease in offspring. [ABSTRACT FROM AUTHOR]