Search

Abstract Background It remains unclear which early gestational biomarkers can be used in predicting later development of gestational diabetes mellitus (GDM). We sought to identify the optimal combination of early gestational biomarkers in predicting GDM in machine learning (ML) models. Methods This was a nested case-control study including 100 pairs of GDM and euglycemic (control) pregnancies in the Early Life Plan cohort in Shanghai, China. High sensitivity C reactive protein, sex hormone binding globulin, insulin-like growth factor I, IGF binding protein 2 (IGFBP-2), total and high molecular weight adiponectin and glycosylated fibronectin concentrations were measured in serum samples at 11–14 weeks of gestation. Routine first-trimester blood test biomarkers included fasting plasma glucose (FPG), serum lipids and thyroid hormones. Five ML models [stepwise logistic regression, least absolute shrinkage and selection operator (LASSO), random forest, support vector machine and k-nearest neighbor] were employed to predict GDM. The study subjects were randomly split into two sets for model development (training set, n = 70 GDM/control pairs) and validation (testing set: n = 30 GDM/control pairs). Model performance was evaluated by the area under the curve (AUC) in receiver operating characteristics. Results FPG and IGFBP-2 were consistently selected as predictors of GDM in all ML models. The random forest model including FPG and IGFBP-2 performed the best (AUC 0.80, accuracy 0.72, sensitivity 0.87, specificity 0.57). Adding more predictors did not improve the discriminant power. Conclusion The combination of FPG and IGFBP-2 at early gestation (11–14 weeks) could predict later development of GDM with moderate discriminant power. Further validation studies are warranted to assess the utility of this simple combination model in other independent cohorts.

Introduction: Anaemia is a significant global health concern, particularly among pregnant women. This condition, primarily caused by Iron Deficiency (ID), poses risks to both maternal and foetal health. However, interpreting iron status through biochemical tests faces challenges. While serum ferritin concentration is a specific indicator of ID, its accuracy can be compromised by factors like inflammation. Serum Soluble Transferrin Receptor (sTfR) has shown promise in accurately diagnosing anaemia, especially in pregnant women, as it remains unaffected by pregnancy-related changes. Nonetheless, studies on its efficiency have yielded mixed results. Aim: To study the prevalence of Iron Deficiency Anaemia (IDA) among pregnant women and also to evaluate the accuracy of sTfR levels and the sTfR/Log Ferritin Index as diagnostic markers in predicting IDA among pregnant women. Materials and Methods: This cross-sectional study was conducted at NEIGRIHMS, Shillong, Meghalaya, India, between April 2021 and November 2022. A total of 92 pregnant women in their first trimester were included in the study. An automated clinical chemistry analyser measured serum iron and high-sensitivity C-Reactive Protein (hsCRP). Serum ferritin and sTfR levels were assessed via chemiluminescence assay. Sensitivity and specificity of sTfR levels and the sTfR/Log Ferritin Index in predicting IDA were determined utilising the Receiver Operating Characteristic (ROC) curve. Results: Most participants, 38 individuals (41.3%), were aged 20 to 25 years. The prevalence of anaemia was observed in eight individuals, comprising 8.7%, with sTfR proving highly sensitive (87.5%) and specific (75%) for IDA at 25.24 nmol/L. Both sTfR (r=-0.360) and sTfR-ferritin Index (r=-0.344) had significant negative correlations with Haemoglobin (Hb) (p-value

Background: It remains unclear which early gestational biomarkers can be used in predicting later development of gestational diabetes mellitus (GDM). We sought to identify the optimal combination of early gestational biomarkers in predicting GDM in machine learning (ML) models. Methods: This was a nested case-control study including 100 pairs of GDM and euglycemic (control) pregnancies in the Early Life Plan cohort in Shanghai, China. High sensitivity C reactive protein, sex hormone binding globulin, insulin-like growth factor I, IGF binding protein 2 (IGFBP-2), total and high molecular weight adiponectin and glycosylated fibronectin concentrations were measured in serum samples at 11–14 weeks of gestation. Routine first-trimester blood test biomarkers included fasting plasma glucose (FPG), serum lipids and thyroid hormones. Five ML models [stepwise logistic regression, least absolute shrinkage and selection operator (LASSO), random forest, support vector machine and k-nearest neighbor] were employed to predict GDM. The study subjects were randomly split into two sets for model development (training set, n = 70 GDM/control pairs) and validation (testing set: n = 30 GDM/control pairs). Model performance was evaluated by the area under the curve (AUC) in receiver operating characteristics. Results: FPG and IGFBP-2 were consistently selected as predictors of GDM in all ML models. The random forest model including FPG and IGFBP-2 performed the best (AUC 0.80, accuracy 0.72, sensitivity 0.87, specificity 0.57). Adding more predictors did not improve the discriminant power. Conclusion: The combination of FPG and IGFBP-2 at early gestation (11–14 weeks) could predict later development of GDM with moderate discriminant power. Further validation studies are warranted to assess the utility of this simple combination model in other independent cohorts. Novelty statements: It remains unclear which early gestational biomarkers can be used in predicting later development of gestational diabetes mellitus. The present study demonstrates that the combination of fasting plasma glucose and insulin-like growth factor binding protein 2 at early gestation can predict later development of gestational diabetes with moderate discriminant power. [ABSTRACT FROM AUTHOR]

Introduction: Anaemia is a significant global health concern, particularly among pregnant women. This condition, primarily caused by Iron Deficiency (ID), poses risks to both maternal and foetal health. However, interpreting iron status through biochemical tests faces challenges. While serum ferritin concentration is a specific indicator of ID, its accuracy can be compromised by factors like inflammation. Serum Soluble Transferrin Receptor (sTfR) has shown promise in accurately diagnosing anaemia, especially in pregnant women, as it remains unaffected by pregnancy-related changes. Nonetheless, studies on its efficiency have yielded mixed results. Aim: To study the prevalence of Iron Deficiency Anaemia (IDA) among pregnant women and also to evaluate the accuracy of sTfR levels and the sTfR/Log Ferritin Index as diagnostic markers in predicting IDA among pregnant women. Materials and Methods: This cross-sectional study was conducted at NEIGRIHMS, Shillong, Meghalaya, India, between April 2021 and November 2022. A total of 92 pregnant women in their first trimester were included in the study. An automated clinical chemistry analyser measured serum iron and high-sensitivity C-Reactive Protein (hsCRP). Serum ferritin and sTfR levels were assessed via chemiluminescence assay. Sensitivity and specificity of sTfR levels and the sTfR/Log Ferritin Index in predicting IDA were determined utilising the Receiver Operating Characteristic (ROC) curve. Results: Most participants, 38 individuals (41.3%), were aged 20 to 25 years. The prevalence of anaemia was observed in eight individuals, comprising 8.7%, with sTfR proving highly sensitive (87.5%) and specific (75%) for IDA at 25.24 nmol/L. Both sTfR (r=-0.360) and sTfR-ferritin Index (r=-0.344) had significant negative correlations with Haemoglobin (Hb) (p-value<0.001), while ferritin (r=0.156) didn't correlate significantly with Hb (p-value=0.136). Notably, CRP didn't affect sTfR levels, enhancing its reliability. Conclusion: sTfR levels and the sTfR-Ferritin index were significantly higher in pregnant women with IDA. They exhibited greater sensitivity and specificity compared to serum ferritin in detecting IDA. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we elucidated the changes in metabolites and microbial communities in pregnant ewes during early gestation, and tried to find new biomarkers to predict early pregnancy in sheep. Significant differences were found in the blood biochemical parameters and blood metabolites, but not in the faecal microbial community. At the same time, five potential pregnancy biomarkers were found to predict early pregnancy in ewes. These detected differences will provide a scientific theoretical basis for the rational nutritional regulation of farmers, and these newly discovered biomarkers will promote the development of technology for detecting early pregnancy in sheep in highly cold areas. Ewes undergo complex metabolic changes during pregnancy. Understanding the specific process of these changes is a necessary prerequisite in ewes for regulating and intervening in order to maintain pregnancies. However, there have been relatively few studies on the specific changes that occur in nutritional metabolism in pregnant ewes during early gestation, especially for some landrace ewes in highly cold areas. Therefore, this study aimed to (1) elucidate the changes in metabolites and microbial communities in pregnant ewes during early gestation using metabolomics and 16S ribosomal RNA gene (rDNA) amplicon sequencing approaches, and to (2) discover novel early pregnancy-induced biomarkers in the blood and faeces. Rams were placed together with ewes on D0 and removed on D45. During early gestation, blood and faecal samples were collected from ewes in a highly cold area for analysing the metabolites and microbial communities; these were retrospectively classified as the early gestation pregnant (EP) ewe group or the nonpregnant (NP) ewe group based on the lambing status recorded during the expected delivery period. The differences in the plasma biochemical parameters, plasma metabolites, and faecal microbial communities of pregnant and nonpregnant ewes were characterised. The GC, IL-6, O-acetyl-l-serine, L-glutamine, and 6-acetamido-2-oxohexanoic acid were screened out as potential biomarkers for evaluating the occurrence of early pregnancy. These novel early pregnancy-induced metabolites discovered in ewes might allow for the development of technologies to detect early pregnancies in sheep in highly cold areas. [ABSTRACT FROM AUTHOR]

BackgroundMultiecho gradient-echo Cartesian MRI characterizes placental oxygenation by quantifying R2* . Previous research was performed at 1.5T using breath-held 2D imaging during later gestational age (GA).PurposeTo evaluate the accuracy and repeatability of a free-breathing (FB) 3D multiecho gradient-echo stack-of-radial technique (radial) for placental R2* mapping at 3T and report placental R2* during early GA.Study typeProspective.PopulationThirty subjects with normal pregnancies and three subjects with ischemic placental disease (IPD) were scanned twice: between 14-18 and 19-23 weeks GA.Field strength3T.SequenceFB radial.AssessmentLinear correlation (concordance coefficient, ρc ) and Bland-Altman analyses (mean difference, MD) were performed to evaluate radial R2* mapping accuracy compared to Cartesian in a phantom. Radial R2* mapping repeatability was characterized using the coefficient of repeatability (CR) between back-to-back scans. The mean and spatial coefficient of variation (CV) of R2* was determined for all subjects, and separately for anterior and posterior placentas, at each GA range.Statistical testsρc was tested for significance. Differences in mean R2* and CV were tested using Wilcoxon Signed-Rank and Rank-Sum tests. P < 0.05 was considered significant. Z-scores for the IPD subjects were determined.ResultsFB radial demonstrated accurate (ρc ≥0.996; P < 0.001; |MD|

Ewes undergo complex metabolic changes during pregnancy. Understanding the specific process of these changes is a necessary prerequisite in ewes for regulating and intervening in order to maintain pregnancies. However, there have been relatively few studies on the specific changes that occur in nutritional metabolism in pregnant ewes during early gestation, especially for some landrace ewes in highly cold areas. Therefore, this study aimed to (1) elucidate the changes in metabolites and microbial communities in pregnant ewes during early gestation using metabolomics and 16S ribosomal RNA gene (rDNA) amplicon sequencing approaches, and to (2) discover novel early pregnancy-induced biomarkers in the blood and faeces. Rams were placed together with ewes on D0 and removed on D45. During early gestation, blood and faecal samples were collected from ewes in a highly cold area for analysing the metabolites and microbial communities; these were retrospectively classified as the early gestation pregnant (EP) ewe group or the nonpregnant (NP) ewe group based on the lambing status recorded during the expected delivery period. The differences in the plasma biochemical parameters, plasma metabolites, and faecal microbial communities of pregnant and nonpregnant ewes were characterised. The GC, IL-6, O-acetyl-l-serine, L-glutamine, and 6-acetamido-2-oxohexanoic acid were screened out as potential biomarkers for evaluating the occurrence of early pregnancy. These novel early pregnancy-induced metabolites discovered in ewes might allow for the development of technologies to detect early pregnancies in sheep in highly cold areas.

The goal of the study was to establish an efficient first-trimester predictive model for any type of preterm birth before 37 gestational weeks (spontaneous preterm birth (PTB) or preterm prelabor rupture of membranes (PPROM)) in the absence of other pregnancy-related complications, such as gestational hypertension, preeclampsia, fetal growth restriction, or small for gestational age. The retrospective study was performed in the period from 11/2012 to 3/2020. Peripheral blood samples were collected from 6440 Caucasian individuals involving 41 PTB and 65 PPROM singleton pregnancies. A control group with 80 singleton term pregnancies was selected on the basis of equal sample-storage time. A combination of only six microRNAs (miR-16-5p, miR-21-5p, miR-24-3p, miR-133a-3p, miR-155-5p, and miR-210-3p; AUC 0.812, p < 0.001, 70.75% sensitivity, 78.75% specificity, cut-off > 0.652) could predict preterm delivery before 37 gestational weeks in early stages of gestation in 52.83% of pregnancies with a 10.0% FPR. This predictive model for preterm birth based on aberrant microRNA expression profile was further improved via implementation of maternal clinical characteristics (maternal age and BMI at early stages of gestation, infertility treatment with assisted reproductive technology, occurrence of preterm delivery before 37 gestational weeks in previous pregnancy(ies), and presence of any kind of autoimmune disease (rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid syndrome, type 1 diabetes mellitus, or other autoimmune disease)). With this model, 69.81% of pregnancies destined to deliver before 37 gestational weeks were identified with a 10.0% FPR at early stages of gestation. When other clinical variables as well as those mentioned above—such as positive first-trimester screening for early preeclampsia with onset before 34 gestational weeks and/or fetal growth restriction with onset before 37 gestational weeks using the Fetal Medicine Foundation algorithm, as well as positive first-trimester screening for spontaneous preterm birth with onset before 34 gestational weeks using the Fetal Medicine Foundation algorithm—were added to the predictive model for preterm birth, the predictive power was even slightly increased to 71.70% with a 10.0% FPR. Nevertheless, we prefer to keep the first-trimester screening for any type of preterm birth occurring before 37 gestational weeks in the absence of other pregnancy-related complications as simple as possible. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the effects of feeding heifers a vitamin and mineral supplement and targeting divergent rates of weight gain during early gestation on the fetal liver amino acid, carbohydrate, and energy profile at d 83 of gestation. Seventy-two crossbred Angus heifers were randomly assigned in a 2 × 2 factorial arrangement to one of four treatments comprising the main effects of vitamin and mineral supplementation (VTM or NOVTM) and feeding to achieve different rates of weight gain (low gain [LG] 0.28 kg/day vs. moderate gain [MG] 0.79 kg/day). Thirty-five gestating heifers with female fetuses were ovariohysterectomized on d 83 of gestation and fetal liver was collected and analyzed by reverse phase UPLC-tandem mass spectrometry with positive and negative ion mode electrospray ionization, as well as by hydrophilic interaction liquid chromatography UPLC-MS/MS with negative ion mode ESI for compounds of known identity. The Glycine, Serine, and Threonine metabolism pathway and the Leucine, Isoleucine, and Valine metabolism pathway had a greater total metabolite abundance in the liver of the NOVTM-LG group and least in the VTM-LG group (p < 0.01). Finally, both the TCA Cycle and Oxidative Phosphorylation pathways within the Energy Metabolism superpathway were differentially affected by the main effect of VTM, where the TCA cycle metabolites were greater (p = 0.04) in the NOVTM fetal livers and the Oxidative Phosphorylation biochemicals were greater (p = 0.02) in the fetal livers of the VTM supplemented heifers. These data demonstrate that the majority of metabolites that are affected by rate of weight gain or vitamin/mineral supplementation are decreased in heifers on a greater rate of weight gain or vitamin/mineral supplementation. [ABSTRACT FROM AUTHOR]

The aim of the study was to determine if aberrant expression profile of cardiovascular disease associated microRNAs would be able to predict within 10 to 13 weeks of gestation preterm delivery such as spontaneous preterm birth (PTB) or preterm prelabor rupture of membranes (PPROM) in the absence of other pregnancy-related complications (gestational hypertension, preeclampsia, fetal growth restriction, or small for gestational age). In addition, we assessed if aberrant expression profile of cardiovascular disease associated microRNAs would be able to predict preterm delivery before and after 34 weeks of gestation. The retrospective study was performed within the period November 2012 to March 2020. Whole peripheral blood samples were collected from 6440 Caucasian individuals involving 41 PTB and 65 PPROM singleton pregnancies. A control group, 80 singleton term pregnancies, was selected on the base of equal sample storage time. Gene expression of 29 selected cardiovascular disease associated microRNAs was studied using real-time RT-PCR. Downregulation of miR-16-5p, miR-20b-5p, miR-21-5p, miR-24-3p, miR-26a-5p, miR-92a-3p, miR-126-3p, miR-133a-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-210-3p, miR-221-3p and miR-342-3p was observed in pregnancies with preterm delivery before 37 (≤36 + 6/7) weeks of gestation. Majority of downregulated microRNAs (miR-16-5p, miR-24-3p, miR-26a-5p, miR-92a-3p, miR-133a-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-210-3p, and miR-342-3p) was associated with preterm delivery occurring before 37 (≤36 + 6/7) weeks of gestation. The only miR-210-3p was downregulated in pregnancies with preterm delivery before 34 (≤33 + 6/7) weeks of gestation. The type of preterm delivery also had impact on microRNA gene expression profile. Downregulation of miR-24-3p, miR-92a-3p, miR-155-5p, and miR-210-3p was a common feature of PTB and PPROM pregnancies. Downregulation of miR-16-5p, miR-20b-5p, miR-26a-5p, miR-126-3p, miR-133a-3p, miR-146a-5p, miR-221-3p, and miR-342-3p appeared just in PTB pregnancies. No microRNA was uniquely dysregulated in PPROM pregnancies. The combination of 12 microRNAs (miR-16-5p, miR-20b-5p, miR-21-5p, miR-24-3p, miR-26a-5p, miR-92a-3p, miR-133a-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-210-3p, and miR-342-3p, AUC 0.818, p < 0.001, 74.53% sensitivity, 75.00% specificity, cut off > 0.634) equally as the combination of 6 microRNAs (miR-16-5p, miR-21-5p, miR-24-3p, miR-133a-3p, miR-155-5p, and miR-210-3p, AUC 0.812, p < 0.001, 70.75% sensitivity, 78.75% specificity, cut off > 0.652) can predict preterm delivery before 37 weeks of gestation in early stages of gestation in 52.83% pregnancies at 10.0% FPR. Cardiovascular disease associated microRNAs represent promising biomarkers with very good diagnostical potential to be implemented into the current routine first trimester screening programme to predict preterm delivery. [ABSTRACT FROM AUTHOR]

A recent study reported the existence of a diverse microbiota in 5-to-7-month-old calf fetuses, suggesting that colonization of the bovine gut with so-called "pioneer" microbiota may begin during mid-gestation. In the present study, we investigated 1) the presence of microbiota in bovine fetuses at early gestation (12 weeks), and 2) whether the fetal microbiota is influenced by the maternal rate of gain or dietary supplementation with vitamins and minerals (VTM) during early gestation. Amniotic and allantoic fluids, and intestinal and placental (cotyledon) tissue samples obtained from fetuses (n = 33) on day 83 of gestation were processed for the assessment of fetal microbiota using 16S rRNA gene sequencing. The sequencing results revealed that a diverse and complex microbial community was present in each of these fetal compartments evaluated. Allantoic and amniotic fluids, and fetal intestinal and placenta microbiota each had distinctly different (0.047 ≥ R 2 ≥ 0.019, P ≤ 0.031) microbial community structures. Allantoic fluid had a greater (P < 0.05) microbial richness (number of OTUs) (Mean 122) compared to amniotic fluid (84), intestine (63), and placenta (66). Microbial diversity (Shannon index) was similar for the intestinal and placental samples, and both were less diverse compared with fetal fluid microbiota (P < 0.05). Thirty-nine different archaeal and bacterial phyla were detected across all fetal samples, with Proteobacteria (55%), Firmicutes (16.2%), Acidobacteriota (13.6%), and Bacteroidota (5%) predominating. Among the 20 most relatively abundant bacterial genera, Acidovorax , Acinetobacter , Brucella , Corynebacterium , Enterococcus , Exiguobacterium , and Stenotrophomonas differed by fetal sample type (P < 0.05). A total of 55 taxa were shared among the four different microbial communities. qPCR of bacteria in the intestine and placenta samples as well as scanning electron microscopy imaging of fetal fluids provided additional evidence for the presence of a microbiota in these samples. Minor effects of maternal rate of gain and VTM supplementation, and their interactions on microbial richness and composition were detected. Overall, the results of this study indicate that colonization with pioneer microbiota may occur during early gestation in bovine fetuses, and that the maternal nutritional regime during gestation may influence the early fetal microbiota. [ABSTRACT FROM AUTHOR]

A recent study reported the existence of a diverse microbiota in 5-to-7-month-old calf fetuses, suggesting that colonization of the bovine gut with so-called “pioneer” microbiota may begin during mid-gestation. In the present study, we investigated 1) the presence of microbiota in bovine fetuses at early gestation (12 weeks), and 2) whether the fetal microbiota is influenced by the maternal rate of gain or dietary supplementation with vitamins and minerals (VTM) during early gestation. Amniotic and allantoic fluids, and intestinal and placental (cotyledon) tissue samples obtained from fetuses (n = 33) on day 83 of gestation were processed for the assessment of fetal microbiota using 16S rRNA gene sequencing. The sequencing results revealed that a diverse and complex microbial community was present in each of these fetal compartments evaluated. Allantoic and amniotic fluids, and fetal intestinal and placenta microbiota each had distinctly different (0.047 ≥ R2 ≥ 0.019, P ≤ 0.031) microbial community structures. Allantoic fluid had a greater (P < 0.05) microbial richness (number of OTUs) (Mean 122) compared to amniotic fluid (84), intestine (63), and placenta (66). Microbial diversity (Shannon index) was similar for the intestinal and placental samples, and both were less diverse compared with fetal fluid microbiota (P < 0.05). Thirty-nine different archaeal and bacterial phyla were detected across all fetal samples, with Proteobacteria (55%), Firmicutes (16.2%), Acidobacteriota (13.6%), and Bacteroidota (5%) predominating. Among the 20 most relatively abundant bacterial genera, Acidovorax, Acinetobacter, Brucella, Corynebacterium, Enterococcus, Exiguobacterium, and Stenotrophomonas differed by fetal sample type (P < 0.05). A total of 55 taxa were shared among the four different microbial communities. qPCR of bacteria in the intestine and placenta samples as well as scanning electron microscopy imaging of fetal fluids provided additional evidence for the presence of a microbiota in these samples. Minor effects of maternal rate of gain and VTM supplementation, and their interactions on microbial richness and composition were detected. Overall, the results of this study indicate that colonization with pioneer microbiota may occur during early gestation in bovine fetuses, and that the maternal nutritional regime during gestation may influence the early fetal microbiota.

Background: Several prognostic models for gestational diabetes mellitus (GDM) are provided in the literature; however, their clinical significance has not been thoroughly evaluated, especially with regard to application at early gestation and in accordance with the most recent diagnostic criteria. This external validation study aimed to assess the predictive accuracy of published risk estimation models for the later development of GDM at early pregnancy. Methods: In this cohort study, we prospectively included 1132 pregnant women. Risk evaluation was performed before 16 + 0 weeks of gestation including a routine laboratory examination. Study participants were followed‐up until delivery to assess GDM status according to the IADPSG 2010 diagnostic criteria. Fifteen clinical prediction models were calculated according to the published literature. Results: Gestational diabetes mellitus was diagnosed in 239 women, that is 21.1% of the study participants. Discrimination was assessed by the area under the ROC curve and ranged between 60.7% and 76.9%, corresponding to an acceptable accuracy. With some exceptions, calibration performance was poor as most models were developed based on older diagnostic criteria with lower prevalence and therefore tended to underestimate the risk of GDM. The highest variable importance scores were observed for history of GDM and routine laboratory parameters. Conclusions: Most prediction models showed acceptable accuracy in terms of discrimination but lacked in calibration, which was strongly dependent on study settings. Simple biochemical variables such as fasting glucose, HbA1c and triglycerides can improve risk prediction. One model consisting of clinical and laboratory parameters showed satisfactory accuracy and could be used for further investigations. [ABSTRACT FROM AUTHOR]

The goal of the study was to establish an efficient first-trimester predictive model for any type of preterm birth before 37 gestational weeks (spontaneous preterm birth (PTB) or preterm prelabor rupture of membranes (PPROM)) in the absence of other pregnancy-related complications, such as gestational hypertension, preeclampsia, fetal growth restriction, or small for gestational age. The retrospective study was performed in the period from 11/2012 to 3/2020. Peripheral blood samples were collected from 6440 Caucasian individuals involving 41 PTB and 65 PPROM singleton pregnancies. A control group with 80 singleton term pregnancies was selected on the basis of equal sample-storage time. A combination of only six microRNAs (miR-16-5p, miR-21-5p, miR-24-3p, miR-133a-3p, miR-155-5p, and miR-210-3p; AUC 0.812, p < 0.001, 70.75% sensitivity, 78.75% specificity, cut-off > 0.652) could predict preterm delivery before 37 gestational weeks in early stages of gestation in 52.83% of pregnancies with a 10.0% FPR. This predictive model for preterm birth based on aberrant microRNA expression profile was further improved via implementation of maternal clinical characteristics (maternal age and BMI at early stages of gestation, infertility treatment with assisted reproductive technology, occurrence of preterm delivery before 37 gestational weeks in previous pregnancy(ies), and presence of any kind of autoimmune disease (rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid syndrome, type 1 diabetes mellitus, or other autoimmune disease)). With this model, 69.81% of pregnancies destined to deliver before 37 gestational weeks were identified with a 10.0% FPR at early stages of gestation. When other clinical variables as well as those mentioned above—such as positive first-trimester screening for early preeclampsia with onset before 34 gestational weeks and/or fetal growth restriction with onset before 37 gestational weeks using the Fetal Medicine Foundation algorithm, as well as positive first-trimester screening for spontaneous preterm birth with onset before 34 gestational weeks using the Fetal Medicine Foundation algorithm—were added to the predictive model for preterm birth, the predictive power was even slightly increased to 71.70% with a 10.0% FPR. Nevertheless, we prefer to keep the first-trimester screening for any type of preterm birth occurring before 37 gestational weeks in the absence of other pregnancy-related complications as simple as possible.

Background: In clinical practice, gestational diabetes mellitus (GDM) is treated as a homogenous disease but emerging evidence suggests that the diagnosis of GDM possibly comprises different metabolic entities. In this study, we aimed to assess early pregnancy characteristics of gestational diabetes mellitus entities classified according to the presence of fasting and/or post‐load hyperglycaemia in the diagnostic oral glucose tolerance test performed at mid‐gestation. Methods: In this prospective cohort study, 1087 pregnant women received a broad risk evaluation and laboratory examination at early gestation and were later classified as normal glucose tolerant (NGT), as having isolated fasting hyperglycaemia (GDM‐IFH), isolated post‐load hyperglycaemia (GDM‐IPH) or combined hyperglycaemia (GDM‐CH) according to oral glucose tolerance test results. Participants were followed up until delivery to assess data on pharmacotherapy and pregnancy outcomes. Results: Women affected by elevated fasting and post‐load glucose concentrations (GDM‐CH) showed adverse metabolic profiles already at beginning of pregnancy including a higher degree of insulin resistance as compared to women with normal glucose tolerance and those with isolated defects (especially GDM‐IPH). The GDM‐IPH subgroup had lower body mass index at early gestation and required glucose‐lowering medications less often (28.9%) as compared to GDM‐IFH (47.8%, P =.019) and GDM‐CH (54.5%, P =.005). No differences were observed in pregnancy outcome data. Conclusions: Women with fasting hyperglycaemia, especially those with combined hyperglycaemia, showed an unfavourable metabolic phenotype already at early gestation. Therefore, categorization based on abnormal oral glucose tolerance test values provides a practicable basis for clinical risk stratification. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the effects of feeding heifers a vitamin and mineral supplement and targeting divergent rates of weight gain during early gestation on the fetal liver amino acid, carbohydrate, and energy profile at d 83 of gestation. Seventy-two crossbred Angus heifers were randomly assigned in a 2 × 2 factorial arrangement to one of four treatments comprising the main effects of vitamin and mineral supplementation (VTM or NOVTM) and feeding to achieve different rates of weight gain (low gain [LG] 0.28 kg/day vs. moderate gain [MG] 0.79 kg/day). Thirty-five gestating heifers with female fetuses were ovariohysterectomized on d 83 of gestation and fetal liver was collected and analyzed by reverse phase UPLC-tandem mass spectrometry with positive and negative ion mode electrospray ionization, as well as by hydrophilic interaction liquid chromatography UPLC-MS/MS with negative ion mode ESI for compounds of known identity. The Glycine, Serine, and Threonine metabolism pathway and the Leucine, Isoleucine, and Valine metabolism pathway had a greater total metabolite abundance in the liver of the NOVTM-LG group and least in the VTM-LG group (p < 0.01). Finally, both the TCA Cycle and Oxidative Phosphorylation pathways within the Energy Metabolism superpathway were differentially affected by the main effect of VTM, where the TCA cycle metabolites were greater (p = 0.04) in the NOVTM fetal livers and the Oxidative Phosphorylation biochemicals were greater (p = 0.02) in the fetal livers of the VTM supplemented heifers. These data demonstrate that the majority of metabolites that are affected by rate of weight gain or vitamin/mineral supplementation are decreased in heifers on a greater rate of weight gain or vitamin/mineral supplementation.

Maternal nutrition affects the development of the fetus and postnatal performance of the calf. Methionine may play a critical role in developmental programming and is likely deficient in beef cows fed low-quality forage. The objective of this study was to determine the effect of metabolizable methionine supply to lactating beef cows during the periconception period on performance of cows, calves, and subsequent offspring. This project involved two consecutive production cycles commencing at calving in which dietary treatments were fed to cows during the periconception period along with measurements on cows and initial calves in Production Cycle 1, and measurements on subsequent calves in Production Cycle 2. Brangus-Angus crossbred lactating beef cows (N = 108; age = 6.4 (2.8) year) were stratified by previous calving date and assigned to one of three supplements: (1) control, molasses plus urea at 2.72 kg/day as fed, (2) fishmeal, 2.27 kg/day molasses plus urea plus 0.33 kg/day as fed of fishmeal, and (3) methionine, 2.72 kg/day of molasses plus urea plus 9.5 g/day of 2-hydroxy-4-(methylthio)-butanoic acid. Cows were fed supplements and low-quality limpograss (Hemarthria altissima) hay while grazing dormant bahiagrass (Paspalum notatum Flüggé) pastures during the 115-day periconception period from December 2014 to April 2015 in Production Cycle 1 only. Body weight change and milk yield of cows were measured during the periconception period in Production Cycle 1. Body weight of calves was measured at birth and weaning in both production cycles. Following weaning in Production Cycle 2, eight subsequent steer calves per treatment were individually housed for a 42-day metabolism experiment. Treatment did not affect (P > 0.10) BW change of cows, but cows fed methionine tended (P = 0.09) to produce more energy-corrected milk than control and fishmeal. Treatment did not affect (P > 0.10) 205-day adjusted weaning weight of calves in either production cycle. During the metabolism experiment, subsequent calves from dams fed fishmeal and methionine gained faster (P

This study determined the effect of orexin B (OXB) on the porcine endometrial transcriptome during the embryo attachment phase. Microarray analyses of gene ontology (GO), biological pathways, networks and differentially expressed genes (DEG) were performed. Orexin B influenced the expression of 887 genes (fold change > 1.2; p <.05): 620 genes were up‐regulated, and 267 were down‐regulated. The analysis of the relationship between DEG revealed that OXB interacts with genes linked with processes such as cell hormone binding, regulation of hormone levels, lipid transport, steroid metabolic processes, the apoptotic signalling pathway and the acute inflammatory response, which are pivotal for reproductive success. Orexin B played a bivalent role in the early‐pregnant uterus by limiting the pregnancy outcome, promoting embryo development, suppressing the immune system and, consequently, preventing embryo rejection. These findings suggest that OXB could be responsible for the proper course of gestation by adapting litter size to the metabolic status of the maternal organism. [ABSTRACT FROM AUTHOR]

Aim of study: To evaluate the impact of the feed level during the first month of gestation on body weight evolution, backfat and loin muscle depths and reproductive performances in highly prolific sows. Area of study: Galicia (Northwestern Spain). Material and methods: Thirty-six Danbred sows were assigned to three experimental groups (n=12) receiving, from day 1 to 30 of pregnancy, 2.5, 3.0 or 3.5 kg/d of a standard diet (8.83 MJ net energy and 138.5 g crude protein/kg). In each group, the number of sows in the second-, third- and fourth-cycle was the same. All animals received, of the same diet, 2.5 kg/d from day 31 to 90 and 3.0 kg/d from day 91 to 107. Seven days prior the parturition, sows were moved to the farrowing-lactating facilities where spent until weaning receiving a common standard lactation diet. At 24 h post-farrowing, litters were standardized to 13 piglets each by cross-fostering. Main results: The optimal feeding level during the first 30 days of gestation was 3.0 kg/d because a lower amount penalized their body weight gain and a higher amount did not improve their fatty reserves. It is worth considering that the increase from 2.5 to 3.5 kg/d generated advantages at birth (higher and more homogenous piglet weights) but also handicaps (lower litter size). The effects were similar irrespective of the cycle number. Research highlights: Different feeding levels during the early pregnancy were tested because it is a critical period. Suppling 3.0 kg/d carried out the best productive and reproductive implications.

The aim of the study was to assess if cardiovascular disease-associated microRNAs would be able to predict during the early stages of gestation (within 10 to 13 weeks) subsequent onset of hypertensive pregnancy-related complications: gestational hypertension (GH) or preeclampsia (PE). Secondly, the goal of the study was to assess if cardiovascular disease-associated microRNAs would be able to detect the presence of chronic hypertension in early pregnancies. The retrospective study was performed on whole peripheral blood samples collected from singleton Caucasian pregnancies within the period November 2012 to March 2020. The case control study, nested in a cohort, involved all women with chronic hypertension (n = 29), all normotensive women that later developed GH (n = 83) or PE with or without fetal growth restriction (FGR) (n = 66), and 80 controls selected on the base of equal sample storage time. Whole peripheral blood profiling was performed with the selection of 29 cardiovascular disease-associated microRNAs using real-time RT-PCR. Upregulation of miR-1-3p (51.72% at 10.0% FPR) was observed in patients with chronic hypertension only. Upregulation of miR-20a-5p (44.83% and 33.33% at 10.0% FPR) and miR-146a-5p (65.52% and 42.42% at 10.0% FPR) was observed in patients with chronic hypertension and normotensive women with later occurrence of PE. Upregulation of miR-181a-5p was detected in normotensive women subsequently developing GH (22.89% at 10.0% FPR) or PE (40.91% at 10.0% FPR). In a part of women with subsequent onset of PE, upregulation of miR-143-3p (24.24% at 10.0% FPR), miR-145-5p (21.21% at 10.0% FPR), and miR-574-3p (27.27% at 10.0% FPR) was also present. The combination of microRNA biomarkers (miR-20a-5p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, and miR-574-3p) can predict the later occurrence of PE in 48.48% of pregnancies at 10.0% FPR in early stages of gestation. The combination of upregulated microRNA biomarkers (miR-1-3p, miR-20a-5p, and miR-146a-5p) is able to identify 72.41% of pregnancies with chronic hypertension at 10.0% FPR in early stages of gestation. Cardiovascular disease-associated microRNAs represent promising biomarkers with very good diagnostical potential to be implemented into the current first trimester screening program to predict later occurrence of PE with or without FGR. The comparison of the predictive results of the routine first trimester screening for PE and/or FGR based on the criteria of the Fetal Medicine Foundation and the first trimester screening for PE wo/w FGR using a panel of six cardiovascular disease-associated microRNAs only revealed that the detection rate of PE increased 1.45-fold (48.48% vs. 33.33%).

We hypothesized that maternal nutrition and day of gestation would influence the abundance of the neutral amino acid transporters SLC1A1, SLC1A5, SLC7A5, SLC38A2, and SLC38A7 in heifer utero-placental tissues. Angus-cross heifers (n = 43) were estrus synchronized and bred via AI. At breeding, heifers were assigned to one of two dietary intake groups (CON = 100% of requirements to achieve 0.45 kg/d gain or restricted heifers (RES) = 60% of CON intake) and ovariohysterectomized on day 16, 34, or 50 of gestation (n = 6 to 9/d). Thus, the experimental design was a completely randomized design with a 2 × 3 factorial arrangement of treatments. Uterine cross sections were taken from the horn ipsilateral to the CL, fixed in 10% NBF, sectioned at 5 µm, and stained for transporters. For each image, the areas of fetal membrane (FM; chorioallantois), endometrium (ENDO), superficial glands (SG), deep glands (DG), and myometrium (MYO) were analyzed separately for relative intensity of fluorescence as an indicator of transporter abundance. Analysis of FM was only conducted on days 34 and 50. In ENDO, SLC7A5 was greater (P < 0.01) in CON compared with RES heifers. In SG, SLC1A1 was greater (P = 0.02) in day 16 RES compared with day 16 CON and days 34 and 50 RES. In DG, SLC1A1 was greater (P = 0.02) on day 16 compared with 50 of gestation. In MYO, SLC1A1 was greater (P = 0.02) in day 50 CON compared with day 16 CON and day 50 RES. Additionally, in MYO SLC38A2 was greater (P = 0.02) in day 16 RES compared with day 16 CON and day 34 RES. In FM, SLC7A5 tended (P = 0.08) to be greater in CON vs RES. Analysis of all uterine tissues on day 16 determined that expression of SLC1A1, SLC1A5, SL38A2, and SL38A7 differed across uterine tissue type (P < 0.01); however, only SLC7A5 tended (P = 0.10) to differ and be greater in CON compared with RES heifers. Analysis of all utero-placental tissues on days 34 and 50 determined that SLC1A1, SLC7A5, SLC38A2, and SLC38A7 were greater (P ≤ 0.03) in CON compared with RES heifers. Furthermore, abundance of all transporters investigated on days 34 and 50 differed across utero-placental tissue types (P < 0.01). These data support our hypothesis that maternal nutrition and day of gestation influence the abundance of neutral amino acid transporters in utero-placental tissues from days 16 to 50 of gestation. Additionally, these data combined with previously published works help further elucidate nutrient supply and demands of the maternal and fetal system during early gestation in beef heifers. [ABSTRACT FROM AUTHOR]

Introduction: Macrophages participate in the regulation immune and morphogenetic events in the placenta. However, these roles remain unclear for placental macrophages (Hofbauer cells). The aims of this study were to characterize the consecutive steps of cytokine production (intracellular synthesis and secretion) in placental macrophages in early and late gestation and to compare the secretory profiles of placental macrophages and villous tissue.Methods: Macrophages and villous tissue were isolated from placentas obtained from normal pregnancies at either 9-12 or 38-40 weeks of gestation. Intracellular cytokines were determined by flow cytometry after staining with monoclonal antibodies. Secreted cytokines were quantified by cytometric bead array and ELISA.Results: Two patterns of cytokine production were revealed in placental macrophages. Cytokines in the first group (IL-1, IL-6, IL-8, IL-10, TNFα) demonstrated low basal production and were stimulated by bacterial endotoxin. Cytokines in the second group (IL-11, IL-17A, IL-17F, TGF-β, VEGF) were characterized by constitutive production and did not respond to stimulation. Gestational age-dependent changes were observed: basal secretion of TNFα and IL-8 increased whereas IL-11 and IL-17 secretion decreased in third-trimester macrophages compared with the first-trimester cells. Comparison of cytokine production at the cellular and tissue levels suggested the contribution of the placental macrophages both in intraplacental and extraplacental cytokine production.Discussion: It would be safe to assume that the two patterns of cytokine production, revealed in our study, correspond to two regulatory roles of placental macrophages: "immune" and "morphogenetic". The inflammatory phenotype of macrophages is attenuated in early gestation and increases with the progression of pregnancy. The cytokines of the first group supposedly contribute to both local and extraplacental levels, whereas the cytokine effects of the second group are more likely confined to the placental tissue. [ABSTRACT FROM AUTHOR]

Introduction. Based on the knowledge of early gestational disorders related to metabolic syndrome (MS), pathogenetically relevant preventive treatment meeting the requirements of perinatal pharmacology can be developed. Aim. To reveal clinical and laboratory characteristics of early pregnancy and develop pathogenetically relevant preventive monotherapy for unfavorable gestational and perinatal outcomes in women with metabolic syndrome. Material and methods. A total of 230 women were investigated and divided into four groups: Group I consisted of 68 pregnant women with MS who refused any preventive measures; Group II comprised 97 women with MS who received periconceptional preventive monotherapy with dydrogesterone, a progestagen; Group III consisted of 35 healthy primigravidas women with physiological course of gestation; Group IV comprised 30 healthy non-pregnant women. Laboratory testing during I–III trimesters allowed to assess the dynamics demonstrated by markers of lipid spectrum, endothelial dysfunction, apoptosis, decidualization, energy metabolism, and immunomodulation. Results. A balance between factors of physiological damage and gestational adaptation in the course of physiological pregnancy has been shown to be of primary significance. In women with MS, embryo-placental dysfunction develops during early pregnancy, and this stage is preceding for major obstetric syndromes. Preventive administration of dydrogesterone in women with MS appeared highly effective: NNT (number needed to treat) was 1.33 (95% CI 0.9–1.8); OR 5.2 (95% CI 4.6–5.7). Conclusion. Pregestational changes and atherogenic profile of gestational process determine the course of early pregnancy in women with MS with the development of embryo-placental dysfunction and major obstetric syndromes. High efficacy in the prevention of unfavorable gestational and perinatal outcomes was shown by preventive dydrogesterone monotherapy.

Abstract Background Intra-uterine crowding (IUC) observed in hyperprolific sows impairs myofiber hyperplasia and overall fetal growth. Arginine supplementation (ARG) in gestation diets has been shown to positively affect litter and muscle development. The study objective was to assess whether the effect of ARG on offspring characteristics, with special emphasis on myofiber hyperplasia, differs under IUC conditions from these responses, because in that situation growth retardation is particularly prevalent due to reduced fetal nutrient supply. Unilateral oviduct ligation (OL) was used as a model for an uncrowded and hyperprolificacy (IN) as a model for a crowded intra-uterine environment. Methods Five OL and five IN sows were fed a diet supplemented daily with either 43 g l-alanine (Ctrl) or 25 g l-arginine from d 14 to 28 of gestation in a cross-over design (two periods: 5th and 6th parity). At farrowing, two male and two female offspring, respectively, with a low and intermediate birth weight (BtW) were selected. After euthanization, the Semitendinosus muscle (STM) was removed and weighed, and the light and dark portions (STMd and STMl) were prepared for myofiber histochemistry using ATPase staining and the entire STM for gene expression analysis of myogenesis-related genes using RT-qPCR. In addition, various organs were removed and weighed. Data were analyzed using the MIXED model in SYSTAT. Results No effect of either IUC or dietary treatment was found in litter characteristics. Offspring of ARG sows displayed a greater muscle area in STM (P < 0.01) as a result of the greater myofiber hyperplasia (P < 0.01). The increase was more distinct in the STMl (P < 0.05) than in the STMd (P = 0.131). Offspring of OL sows were heavier at birth (P < 0.01), had a heavier STM (P < 0.05), liver (P < 0.01) and kidney (P < 0.05), but when expressed relative to birth weight, these differences were absent. In addition, IUC had an effect (P < 0.05) on the expression of one of the myogenesis-related genes investigated. Conclusions Independent from the extent of IUC, ARG improved BtW, muscle and organ weights and myofiber hyperplasia in offspring.

Maternal nutrition is pivotal for proper fetal development, with one-carbon metabolites (OCM) playing a key role in fetal epigenetic programming through DNA and histone methylation. The study aimed to investigate the effects of nutrient restriction and OCM supplementation on fetal liver metabolomics in pregnant beef-heifers, focusing on metabolites and pathways associated with amino acid, vitamin and cofactor, carbohydrate, and energy metabolism at day 63 of gestation. Thirty-one crossbred Angus heifers were artificially inseminated and allocated to 4 nutritional treatments in a 2 × 2 factorial arrangement of treatments, with the 2 factors being dietary intake/rate of gain (control-diet [CON]; 0.60 kg/d ADG, vs. restricted-diet [RES]; -0.23 kg/d ADG) and OCM supplementation (supplemented [+OCM] vs. not supplemented [-OCM]). The resulting treatment groups-CON - OCM, CON + OCM, RES - OCM, and RES + OCM were maintained for 63 day post-breeding. Following this period, fetal liver tissues were collected and subjected to metabolomic analysis using UPLC-tandem mass-spectrometry. We identified 288 metabolites, with the majority (n = 54) being significantly influenced by the main effect of gain (P ≤ 0.05). Moreover, RES showed decreased abundances of most metabolites in pathways such as lysine metabolism; leucine, isoleucine, and valine metabolism; and tryptophan metabolism, compared to CON. Supplementation with OCM vs. no OCM supplementation, resulted in greater abundance of metabolites (P ≤ 0.05) affecting pathways associated with methionine, cysteine, S-adenosylmethionine and taurine metabolism; guanidino and acetamido metabolism; and nicotinate and nicotinamide metabolism. Notably, OCM supplementation with a moderate rate of gain increased the concentrations of ophthalmate, N-acetylglucosamine, and ascorbic-acid 3-sulfate, which are important for proper fetal development (P ≤ 0.05). Nutrient restriction reduced the majority of liver metabolites, while OCM supplementation increased a smaller number of metabolites. Thus, OCM supplementation may be protective of metabolite concentrations in key developmental pathways, which could potentially enhance fetal development under nutrient-restricted conditions., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Abstract The aim of this study was to investigate if transrectal three-dimensional (3D) ultrasound is a reliable technique to measure equine fetal volume (FV) during early gestation in mares. In total 149 warmblood mares were examined once transrectally on days 45 ± 1 of pregnancy with a portable 3D ultrasound device (Voluson® i, GE Healthcare, Zipf, Austria). The following measurements were performed: Two-dimensional (2D) and 3D crown-rump length (CRL), FV using Virtual Organ Computer-aided AnaLysis (VOCAL™) software with rotational angles of 6° and 30°. To analyze intra- and inter-observer reliability (intraclass correlation coefficient (ICC)) and agreement (Bland-Altman's limits of agreement (LoA)) of FV measurements, images from 60 horse fetuses were selected and repeatedly analyzed by the same examiner (A) and by a second examiner (B). The time for each ultrasound examination (2D and 3D) and for the FV measurements was recorded. The 3D measured CRL was larger (P < 0.001) than the 2D CRL. Repeated measurements of 3D CRL showed a higher reliability (ICC = 0.91 (0.88–0.94), P < 0.001) and agreement (mean = 0.13%, 95% LoA: 7.45 to +7.19) compared to reliability (ICC = 0.50 (0.36–0.61), P < 0.001) and agreement (mean = −1.54%, 95% LoA: 23.29 to +20.21) of the CRL measurement in 2D mode. For intra-observer examinations, reliability was highest when using a rotational angle of 30° (ICC = 0.98 (0.97–0.99), P < 0.001). The inter-observer reliability of 3D measurements was good (ICC = 0.85 (0.67–0.92), P < 0.001). The extra time needed to perform the 3D scan ranged from 1 to 9 min and FV measurements lasted 03:30 ± 00:46 and 08:10 ± 01:05, for rotational angles of 30° and 6°, respectively. In conclusion, this study showed a high level of intra- and inter-observer reliability and agreement for FV measurements using VOCAL™. Furthermore, the 6° and 30° rotational angles can be used interchangeably, but test duration, reliability and agreement were better with the 30° rotational step method. The CRL measurements obtained with 3D mode probably reflects the true CRL, compared to the 2D measured CRL. Highlights • Equine fetal volumes can be measured by using 3D ultrasound. • Fetal volume calculation is a feasible technique for equine fetal size measurement. • 3D ultrasound CRL measurement is superior to the conventional 2D measurement. • High level of intra-observer reliability/agreement achieved for volume measurements. [ABSTRACT FROM AUTHOR]

We examined the hypothesis that maternal nutrition and day of gestation would affect the concentrations of AAs and hexoses in bovine utero-placental fluids and maternal serum from days 16 to 50 of gestation. Forty-nine cross-bred Angus heifers were bred via artificial insemination and fed a control diet (CON = 100% of requirements for growth) or a restricted diet (RES = 60% of CON) and ovariohysterectomized on days 16, 34, or 50 of gestation; nonpregnant controls were not bred and ovariohysterectomized on day 16 of the synchronized estrous cycle. The resulting design was a completely randomized design with a 2 × 3 factorial + 1 arrangement of treatments. Maternal serum, histotroph, allantoic fluid, and amniotic fluid were collected at time of ovariohysterectomy. Samples were then analyzed for concentrations of AAs and intermediary metabolites: alanine (Ala), arginine, asparagine (Asn), aspartate (Asp), citrulline, cysteine, glutamine, glutamate (Glu), glycine (Gly), histidine, isoleucine, leucine (Leu), lysine, methionine (Met), ornithine, phenylalanine (Phe), proline (Pro), serine (Ser), threonine (Thr), tryptophan, tyrosine (Tyr), and valine (Val). The concentrations of Gly, Ser, and Thr in maternal serum were greater (P ≤ 0.05) in CON compared with RES. Furthermore, day of gestation affected (P ≤ 0.05) concentrations of Asn, Glu, Phe, Thr, and Tyr in maternal serum. Status of maternal nutrition affected the Asp concentration of histotroph where RES was greater (P = 0.02) than CON. In histotroph, Ala, Leu, Met, and Val concentrations were greater (P ≤ 0.05) on day 50 compared with day 16. Additionally, Glu and Pro concentrations in histotroph were greater (P < 0.01) on days 34 and 50 compared with day 16. A day × treatment interaction was observed for the concentration of Val in allantoic fluid where day 34 CON was greater (P = 0.05) than all other days and nutritional treatments. In addition, the concentration of Gln in amniotic fluid experienced a day × treatment interaction where day 34 RES was greater (P ≤ 0.05) than day 34 CON, which was greater (P ≤ 0.05) than day 50 CON and RES. These data support our hypothesis that day of gestation and maternal nutrition affect the concentrations of various neutral and acidic AA in beef heifer utero-placental fluids and maternal serum from days 16 to 50 of gestation. [ABSTRACT FROM AUTHOR]

Abstract Orexin A belongs to the group of hypothalamic-derived peptides that are involved in a number of processes, such as regulation of energy metabolism, control of food intake and regulation of the reproductive system, by influencing the hypothalamic-pituitary-ovarian axis. Orexin A is also present in the endometrium, myometrium and placenta, which indicates that it may function as an important local regulator of the reproductive functions. The aim of this study was to explore the effects of orexin A on global gene expression in the endometrium of pigs during early gestation, on days 15 to 16 of pregnancy (implantation period). Orexin A altered the expression of 1,242 genes. In this group, 1,104 genes had a fold change greater than 1.2 (P < 0.05). In the group of genes with a fold change that was greater than 1.2, the expression of 457 genes were increased and 647 decreased because of the effects of orexin A. An analysis of the interactions between differentially expressed genes demonstrated that orexin A interacts with genes that potentially encode intracellular signalling pathways and factors regulating reproductive functions in the endometrium. The data from the present study indicate that orexin A affects a number of genes and processes in the endometrium of pregnant pigs and may be regarded as an important regulator of implantation, depending on maternal nutritional status. [ABSTRACT FROM AUTHOR]

Copyright of Journal of the Chinese Society of Animal Science is the property of Chinese Society of Animal Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Fall calving (September to October) cows (n = 189 calvings in 5 replications; body weight [BW] = 626 ± 6 kg, body condition score [BCS] = 4.76 ± 0.06) grazing native dormant range were used to determine the effects of protein supplementation on performance and endocrine function of cows and calves. Cows were individually fed either a control (CON; 1.82 kg/d of 38% crude protein [CP]) or restricted (RES; 0.2 kg/d of 8% CP) protein supplement from mid-November to mid-March for 6 consecutive years. During each year, cows were reassigned dietary treatments according to calving date and BCS, and half of the CON and half of the RES cows remained on the same diets as the previous year and the other halves were assigned to the other diet. Statistical analyses were performed with the general linear model procedure utilizing a 2 x 2 factorial arrangement and a complete randomized design. Cows on CON diets lost less BW from November to January compared with RES cows (-25.9 ± 2.6 and -45.0 ± 2.6 kg, respectively; P < 0.001). Protein supplementation increased plasma concentrations of insulin of CON compared with RES cows during treatment (P < 0.05). Calf birth weight did not differ between prenatal supplemention of CON and RES (P = 0.87). A prenatal x postnatal effect was detected for BW of calves; prenatal RES and postnatal CON calves (RES-CON; 189.4 ± 4.2, P = 0.05) had greater 205-d adjusted weaning weights compared with prenatal RES and postnatal RES (RES-RES) and prenatal CON and postnatal RES (CON-RES) calves (163.0 ± 4.2 and 177.8 ± 4.2 kg, respectively). There was a prenatal x postnatal effect on gain of calves from January to weaning (P = 0.05); RES-CON gained more than RES-RES and CON-RES calves. Adjusted yearling 365-d BW was least (P = 0.02) for RES-RES calves. Prenatal protein supplementation of cows decreased (P = 0.03) final BW of calves at harvest (23 mo). Prenatal and postnatal supplementation of cows did not influence carcass characteristics of calves (P > 0.10). In conclusion, increasing protein supplementation of fall calving beef cows from November to March, during breeding and early pregnancy, reduced BW loss of cows, decreased the interval from calving to pregnancy, increased plasma concentrations of insulin in December, January, and March, and increased plasma insulin-like growth factor-I in December without alteration in pregnancy rate. Reduced protein supplementation prenatally increased BW of calves at harvest. [ABSTRACT FROM AUTHOR]

We hypothesized that both day of gestation and maternal nutrition would alter the relative mRNA expression of neutral and acid AA transporters SLC1A1, SLC1A5, SLC7A5, SLC38A2, and SLC38A7. Crossbred Angus heifers (n = 49) were synchronized, bred via AI, assigned to nutritional treatment (100% of NRC requirements for 0.45 kg/d gain [control heifers {CON}] and 60% of CON [restricted heifers {RES}]), and ovariohysterectomized on d 16, 34, or 50 of gestation (n = 6 to 9/d). Nonbred, nonpregnant (NB-NP) controls were ovariohysterectomized on d 16 of the estrous cycle (n = 6) after synchronization. The resulting arrangement was a 2 × 3 factorial + 1 (CON vs. RES × d 16, 34, or 50 + NB-NP controls). Tissues collected included caruncular endometrium (CAR), intercaruncular endometrium (ICAR), fetal membranes (FM; chorioallantois; d 16 and 34), cotyledonary placenta (COT; d 50 only), intercotyledonary placenta (ICOT; d 50 only), and amnion (AMN; d 50 only]). Relative expression of SLC1A1, SLC1A5, SLC7A5, SLC38A2, and SLC38A7 was determined for each tissue using NB-NP CAR and NB-NP ICAR tissues for the baseline; for FM, endometrium from NB-NP controls served as the baseline. In CAR, no day × treatment interaction was observed (P > 0.05). However, day of gestation affected relative expression of SLC1A1, where expression on d 16 was greater (P < 0.01) than expression on d 34 and 50. Additionally, relative expression of SLC38A2 and SLC38A7 was greater (P ≤ 0.05) in pregnant heifers compared with NB-NP heifers. For ICAR, SLC38A7 was influenced by a day × treatment interaction (P < 0.01), where expression in d 16 RES was greater (P ≤ 0.05) than that of any other day or nutritional treatment. Furthermore, expression in d 16 CON was greater (P ≤ 0.05) than that in d 50 RES, with those in d 34 CON and RES and d 50 CON being intermediate. In addition, SLC1A1 was affected by day of gestation, where expression on d 16 was greater (P < 0.01) than that on d 34 and 50. A day × treatment interaction was not observed (P > 0.05) in FM; however, SLC1A5 expression on d 34 was greater (P = 0.02) than on d 50, with that on d 16 being intermediate. Day of gestation also affected expression of SLC38A2, where expression on d 34 and 50 was greater (P < 0.01) than that on d 16. These data support our hypothesis in that both day of gestation and maternal nutrition affected the relative mRNA expression of AA transporter SLC38A7 in ICAR, whereas day of gestation has a greater effect on the relative mRNA expression of other neutral and acidic AA transporters in the various tissues studied. [ABSTRACT FROM AUTHOR]

Background: Intra-uterine crowding (IUC) observed in hyperprolific sows impairs myofiber hyperplasia and overall fetal growth. Arginine supplementation (ARG) in gestation diets has been shown to positively affect litter and muscle development. The study objective was to assess whether the effect of ARG on offspring characteristics, with special emphasis on myofiber hyperplasia, differs under IUC conditions from these responses, because in that situation growth retardation is particularly prevalent due to reduced fetal nutrient supply. Unilateral oviduct ligation (OL) was used as a model for an uncrowded and hyperprolificacy (IN) as a model for a crowded intra-uterine environment. Methods: Five OL and five IN sows were fed a diet supplemented daily with either 43 g L-alanine (Ctrl) or 25 g L-arginine from d 14 to 28 of gestation in a cross-over design (two periods: 5th and 6th parity). At farrowing, two male and two female offspring, respectively, with a low and intermediate birth weight (BtW) were selected. After euthanization, the Semitendinosus muscle (STM) was removed and weighed, and the light and dark portions (STMd and STMl) were prepared for myofiber histochemistry using ATPase staining and the entire STM for gene expression analysis of myogenesis-related genes using RT-qPCR. In addition, various organs were removed and weighed. Data were analyzed using the MIXED model in SYSTAT. Results: No effect of either IUC or dietary treatment was found in litter characteristics. Offspring of ARG sows displayed a greater muscle area in STM (P < 0.01) as a result of the greater myofiber hyperplasia (P < 0.01). The increase was more distinct in the STMl (P < 0.05) than in the STMd (P = 0.131). Offspring of OL sows were heavier at birth (P < 0.01), had a heavier STM (P < 0.05), liver (P < 0.01) and kidney (P < 0.05), but when expressed relative to birth weight, these differences were absent. In addition, IUC had an effect (P < 0.05) on the expression of one of the myogenesis-related genes investigated. Conclusions: Independent from the extent of IUC, ARG improved BtW, muscle and organ weights and myofiber hyperplasia in offspring. [ABSTRACT FROM AUTHOR]

Adiponectin is secreted by the white adipose tissue and is one of the most important hormones that regulate metabolic homeostasis. The expression of adiponectin and adiponectin receptor genes and proteins in reproductive organs, such as the testes, ovaries, and uterus, suggests that adiponectin is also involved in the regulation of reproductive functions. Changes in the expression of adiponectin and adiponectin receptor genes and proteins in the porcine uterus during the estrous cycle and early pregnancy imply that adiponectin activity may be controlled by the local hormonal milieu. Estrone (E1) and estradiol (E2) are the key steroid hormones that regulate reproductive functions, including the early recognition of pregnancy and implantation. We hypothesize that E1 and E2 may regulate the expression of the adiponectin system in a pregnant uterus. The aim of this study was to investigate the influence of E1 and E2 on the expression of adiponectin and its receptor genes and proteins by porcine endometrial and myometrial explants harvested from gilts (n = 5 per group) on Days 10 to 11, 12 to 13, 15 to 16, and 27 to 28 of pregnancy and on Days 10 to 11 of the estrous cycle. The expression of adiponectin and AdipoRs genes was examined with the real-time polymerase chain reaction, adiponectin secretion was evaluated with the ELISA method, and the expression of receptor proteins was determined using the Western blotting method. The results revealed that both E1 and E2 significantly influenced the expression of the adiponectin gene, hormone secretion in vitro , and the expression of AdipoRs genes and proteins. The influence of E1 and E2 on the expression of the adiponectin system varied in the early gestation, during the estrous cycle and between different stages of gestation. The examined steroids had a tissue-specific and a dose-dependent effect. This is the first ever study to describe the modulatory effect of E1 and E2 on the expression of the adiponectin system in the porcine uterus during early gestation. [ABSTRACT FROM AUTHOR]

We hypothesized that a standing flank ovariohysterectomy procedure could be developed in beef heifers that would provide high quality tissues for addressing critical questions during early pregnancy, while concomitantly keeping livestock stewardship a high priority. To test the hypothesis, we: 1) developed a standing flank ovariohysterectomy procedure for use in beef heifers, and 2) implemented this procedure in a cohort of heifers up to d 50 of pregnancy for tissue collections, documentation of post-surgical recovery, and assessment of feedlot finishing performance. Ovariectomy and cesarean section protocols are well established in research and veterinary medicine and were used as starting points for procedural development. Crossbred Angus heifers (n = 46; ℓ 15 mo of age; BW = 362.3 ± 34.7 kg) were used to develop this new surgical tissue collection technique. Heifers were subjected to the 5-d CO-Synch + CIDR estrous synchronization protocol so ovariohysterectomy occurred at d 16, 22, 28, 34, 40, and 50 of gestation. Key aspects of the standing flank ovariohysterectomy technique included 1) use of local anesthetic for a standing flank incision, 2) locate the uterine and ovarian arteries via blind palpation and ligate them through the broad ligament via an improved clinch knot, 3) cut the ovaries and uterus free from the broad ligament, 4) ligate the cervix and uterine branch of the vaginal artery, and 5) cut through the cervix and remove the reproductive tract. Surgical times, from skin incision to placement of the last suture, were influenced (P = 0.04) by stage of gestation. In pregnant heifers, time decreased from d 22 (120.0 ± 12.0 min) of gestation to d 40 (79.5 ± 12.0 min) of gestation; then increased at d 50 (90.5 ± 14.7 min) of gestation. Using this procedure, we obtained uterine, placental, and embryo/fetal tissues that had experienced limited hypoxia, little or no trauma, and thus were excellent quality for scientific study. All heifers recovered from surgery quickly and were moved to a finishing period. During the finishing period, ovariohysterectomized heifers had a DMI of 13.8 kg, gained 1.99 ± 0.35 kg/d, and had a G:F of 0.145 over 132-d. The standing flank ovariohysterectomy technique represents a new and viable model to economically obtain high quality tissues for investigating critical biological mechanisms during early pregnancy in beef heifers. [ABSTRACT FROM AUTHOR]