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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]

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 ≥ 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]

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]

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]

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]

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]

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]

Background: Multiecho 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).Purpose: To 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 Type: Prospective.Population: Thirty subjects with normal pregnancies and three subjects with ischemic placental disease (IPD) were scanned twice: between 14-18 and 19-23 weeks GA.Field Strength: 3T.Sequence: FB radial.Assessment: Linear 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 Tests: ρc 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.Results: FB radial demonstrated accurate (ρc ≥0.996; P < 0.001; |MD|<0.2s-1 ) and repeatable (CR<4s-1 ) R2* mapping in a phantom, and repeatable (CR≤4.6s-1 ) R2* mapping in normal subjects. At 3T, placental R2* mean ± standard deviation was 12.9s-1  ± 2.7s-1 for 14-18 and 13.2s-1  ± 1.9s-1 for 19-23 weeks GA. The CV was significantly greater (P = 0.043) at 14-18 (0.63 ± 0.12) than 19-23 (0.58 ± 0.13) weeks GA. At 19-23 weeks, the CV was significantly lower (P < 0.001) for anterior (0.49 ± 0.08) than posterior (0.67 ± 0.11) placentas. One IPD subject had a lower mean R2* than normal subjects at both GA ranges (Z<-2).Data Conclusion: FB radial provides accurate and repeatable 3D R2* mapping for the entire placenta at 3T during early GA.Level Of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:291-303. [ABSTRACT FROM AUTHOR]

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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]

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]

During early gestation, nutrients are transported to the developing embryo via transporters in the uterine endometrium and chorioallantois. In the present study, we examined glucose transporters GLUT1 and GLUT3 and the cationic AA transporters SLC7A1, SLC7A2, and SLC7A3 to test the hypotheses that 1) relative mRNA expression of transporters would be different among uteroplacental tissue type as gestation progresses and 2) concentrations of glucose and cationic AA would be different among target sites (placental compartments, serum, and histotrophic) and days of gestation. To test these hypotheses, crossbred Angus heifers (n = 46) were synchronized, bred via AI, and then ovariohysterectomized on d 16, 22, 28, 34, 40, or 50 of gestation (5 to 9/d) or not bred and ovariohysterectomized on d 16 of the synchronized estrous cycle (n = 7) to serve as nonpregnant (NP) controls. Uteroplacental tissues (maternal caruncle [CAR], intercaruncular endometrium [ICAR], and fetal membranes [FM; chorioallantois, d 22 and later]) were collected from the uterine horn ipsilateral to the corpus luteum immediately following ovariohysterectomy. Relative mRNA expression of the glucose transporters and cationic AA transporters was determined for each tissue from d 16 to 50 of gestation and from NP controls. Chorioallantoic, amniotic, and plasma fluids were collected from heifers on d 40 and 50 of gestation to determine concentrations of glucose and cationic AA. Expression of GLUT1 and SLC7A2 showed a tendency (P < 0.10) toward being greater in d 16 ICAR and d 34 ICAR, respectively. Day × tissue interactions (P < 0.05) were present for GLUT3, SLC7A1, and SLC7A3. Expression of GLUT3 was greater in d 50 CAR, expression of SLC7A1 was greater on d 34 in ICAR, and expression of SLC7A3 was greater in CAR tissue on d 34 compared with all other tissues and days of gestation. Glucose concentrations tended (P = 0.10) to be impacted by a day × fluid interaction. A day × fluid interaction (P = 0.01) for arginine concentration was observed, with greater concentrations in allantoic fluid on d 40 compared with all other days and fluid types. These data support our hypothesis that glucose and cationic AA transporters differ in their level of mRNA expression due to day of gestation and uteroplacental tissue type. In addition, concentrations of nutrients were differentially impacted by day, target site, and/or their respective interaction. [ABSTRACT FROM AUTHOR]

Glucose transporter solute carrier family 2 member 14 (GLUT14) is a duplicon of glucose transporter solute carrier family 2 member 3 (GLUT3) with a 95% shared homology to GLUT3 and has not previously been isolated in ruminant uteroplacental tissues. The GLUT3 transporter has been previously isolated in Holstein heifer uterine epithelium but not in ovine epithelium. We hypothesized that GLUT3 and its duplicon GLUT14 would be found in bovine uteroplacental tissues and that maternal nutrition and day of gestation would impact mRNA expression of GLUT3 and GLUT14. Crossbred Angus heifers (n = 49) were estrus synchronized, bred via AI, and assigned to nutritional treatment (CON = 100% of requirements to gain 0.45 kg/d; RES = 60% of CON) at breeding. Ovariohysterectomy was performed on d 16, 34, or 50 of gestation (n = 6 to 9/d); nonpregnant (NP) controls were not bred and ovariohysterectomized on d 16 of the synchronized estrous cycle (n = 6). The resulting treatment arrangement was a 2 x 3 factorial + 1. Uteroplacental tissues (caruncle, CAR; intercaruncular endometrium, ICAR; and fetal membrane [chorioallantois], FM) were obtained from the pregnant uterine horn immediately after ovariohysterectomy. For NP controls, only CAR and ICAR were obtained. There were no day x treatment interactions for GLUT3 or GLUT14 gene expression in CAR, ICAR, or FM. Expression of GLUT3 in CAR was greater (P = 0.03) on d 50 compared with d 16. In ICAR, GLUT3 was greatest (P = 0.02) on d 50 compared with d 16 and 34 of gestation. In FM, GLUT3 was greater (P = 0.04) on d 16 compared with d 50. Expression of GLUT3 was greater (P = 0.05) in pregnant compared with nonpregnant heifers. Additionally, expression of GLUT3 was greater (P = 0.01) on d 34 and 50 compared with d 16. Expression of GLUT14 in CAR was greater (P = 0.03) on d 50 compared to d 16 and 34. In CAR, GLUT14 tended (P = 0.07) to be greater on d 34 and 50 than on d 16 and was greater (P = 0.02) on d 50 than on d 34. There was no effect of treatment for either GLUT3 or GLUT14 in CAR, ICAR, or FM. These data demonstrate that glucose transporters GLUT3 and GLUT14 are expressed in beef heifer uteroplacental tissues and that they are expressed differentially by day of gestation in bovine uteroplacental tissues. [ABSTRACT FROM AUTHOR]

Our objective was to determine the effects of increasing feeding levels for PIC Camborough sows during early gestation on sow and litter performance. A total of 636 sows (PIC Camborough) were randomly assigned at weaning to 1 of 4 treatments that were balanced for weight and caliper scores within parity categories. Treatments consisted of feeding sows with daily feed allowances to meet 85, 115, 145, or 175% of the NRC (2012) maintenance metabolizable energy (MEm) requirement calculated as MEm, kcal/d = 100 × (body weight, kg)0.75. A common corn-soybean meal-distillers dried grains with solubles-based diet with 3,092 kcal of ME/kg and 0.64% standardized ileal digestible lysine was used. Treatments were applied from d 6 to 35 of gestation, after which sows were moved to gestation pens and fed according to body condition through an electronic sow feeder until moved to the farrowing room. Sow was the experimental unit and data were analyzed using generalized linear mixed models with the lmer and glmer functions of R. On average, females were ideal condition at weaning across treatment as determined by the caliper scores. Average feed allowances were 1.6, 2.1, 2.6, and 3.2 kg/day for the 85, 115, 145, and 175% treatments, respectively. Increasing feed allowances reduced (linear, P< 0.05) body weight loss (-13.8, -10.3, -4.7 and -0.5 kg, respectively) and increased caliper score gain (-0.43, -0.03, 0.64, 0.76 units, respectively) from weaning to d 35 of gestation. There was no evidence for treatment effects on farrowing rate, total born, stillborn rate, average litter weight, piglet throughput, or subsequent reproductive performance. In summary, increasing feed allowances to meet 85 to 175% of the MEm requirements during early gestation on Camborough sows resulted in a reduction in body weight loss and an improvement in caliper gain until d 35 of gestation without evidence of impact in reproductive performance. [ABSTRACT FROM AUTHOR]

Early pregnancy is characterized by decidual adaption to the developing embryo involving angiogenesis and vascular growth. Failure of decidual vascular expansion is linked to diseases of pregnancy. Dendritic cells (DC) have been associated with vascular growth during early gestation, though it is unknown whether their capacity to modulate angiogenesis is ubiquitous to all DC subsets. Here, we show that DC normally found associated with the decidual vasculature co-express the C-X-C chemokine receptor type 4 (CXCR4). In addition, we demonstrate that impaired homing of CXCR4DC during early gestation provoked a disorganized decidual vasculature with impaired spiral artery remodeling later in gestation. In contrast, adoptive transfer experiments provided evidence that CXCR4DC are able to rescue early pregnancy by normalizing decidual vascular growth and delivery of pro-angiogenic factors, which results in adequate remodeling of the spiral arteries during placental development. Taken together, our results indicate an important role of CXCR4DC in the regulation of decidual angiogenesis and highlight the importance of the CXCL12/CXCR4 pathway during this process, suggesting that this may represent a key pathway to evaluate during pregnancy pathologies associated with impaired vascular expansion. [ABSTRACT FROM AUTHOR]

Background: The bovine yolk sac derives from visceral endoderm and its development occurs between days 18-23 of gestation. The study of this membrane is important for comparative data and has already been performed in rodents, sheep and in cattle, especially Bos taurus. In species Bos indicus the yolk sac has not quite been studied and is believed that there are morphological differences between these species. The yolk sac undergoes a process of involution and degeneration during embryonic development and none vestige of it is found in late gestation. The period in which occurs the involution of the yolk sac coincides with the period of increased pregnancy loss in cattle, and changes in the morphology of this membrane may indicate the reasons for such high loss rates. Thus, considering that the yolk sac is important for embryonic circulation and metabolic transmission, besides participating actively in the process of cattle placentation, this study aimed characterize morphologically the involution of the bovine yolk sac. Materials, Methods & Results: The early gestational period was determined between days 20 and 70 post-insemination (p.i), according to the exterior characteristics of embryo/fetus. For macroscopic analyzes the uterus was dissected to expose the fetal membranes and subsequently the embryo/fetus was photographed. The samples were fixed for light microscopy and transmission electron microscopy. The yolk sac that emerges from the ventral part of the embryo was prominent and composed by a central part with two thin peripheral projections of different lengths. The bovine yolk sac with about 9 cm on day 25 p. i. of pregnancy permanently decreased its total length during this study. Histologically, the yolk sac is composed of three cell layers: the mesothelium, the mesenchyme and the endoderm. In mesenchyme are found blood islets. In the endoderm are formed cells invaginations toward the mesenchyme originating small canaliculi. The ultrastructure of yolk cells presented many mitochondria, rough endoplasmic reticulum, vesicles, euchromatin and the presence of two nucleoli. Discussion: The real first blood circulation in the bovine is attached with the development of yolk sac, differently from other membranes, such as the corium, that does not present evidence of vascularization by the age of 20-30 days. The erythroblasts found in the yolk sac are related to vasculogenesis and the process of differentiation of blood cells during the erythropoiesis. It could be observed on the histology of the yolk sac, in embryos of 30-50 days old, the presence of canaliculi and small folds of the epithelium. The canaliculi collapse is associated with the degeneration of the endoderm wall of the yolk sac. The organelles present in the endoderm cells of the yolk sac are associated with the function of protein metabolism and in the exchange of substances between the mesenchyme and the mesothelium. For these findings, could be observed that the yolk sac epithelium is found active until the 50th day of gestation, and thereafter regresses. However, remnants of this membrane may be present until the 70th day. These features may represent a presence of an active chorionvitelline placenta in this period responsible for the maintenance of pregnancy whereas the chorioallantoic placenta is not definitively established. [ABSTRACT FROM AUTHOR]

Many women suffer from new or worsening anxiety during pregnancy. In this pilot study, we investigated the effect of timing and severity of prenatal state anxiety symptoms on reduced birth weight. We hypothesized that: (1) Women with state anxiety symptoms during mid-gestation would deliver newborns with lower birth weight in comparison to participants with symptoms in early gestation and (2) compared to women with lower anxiety symptoms (< 50 percentile), women with medium-to-high state anxiety symptoms (> 50 percentile) would have lower birth weight offspring. The sample consisted of the first 30 pregnant women who agreed to participate in this pilot study. We assessed anxiety symptoms, using the State-Trait Anxiety Inventory during early and mid-gestation. We obtained birth weight from clinical charts. A hierarchical multiple regression showed that, after controlling for covariates, state anxiety symptoms in mid-gestation were associated with lower infant birth weight [ F(9, 7) = 20.30, p<.001]. However, birth weight did not differ as a function of the severity of maternal state anxiety [ F(1, 23)=.14, p=.71 and F(1, 24)=1.76, p=.20., respectively]. Clearly, our pilot data need replication. Once statistical significance is established with larger samples, it will be informative to examine the clinical significance of those findings. [ABSTRACT FROM AUTHOR]

Objective. To establish reference intervals for fetal umbilical vein (UV) diameter, UV time averaged maximum velocity (TAMXV) and UV flow (UVBF) at 11 + 0 to 13 plus; 6 weeks of gestation and to determine the intraobserver reliability of these measurements. Methods. We considered, in a cross-sectional study, 162 fetuses from uncomplicated singleton pregnancies at 11 + 0 to 13 + 6 weeks of gestation. UV diameter and TAMXV were measured in its intraabdominal portion by real-time and Doppler ultrasonography and UVBF calculated. Relationships between these parameters and fetal crown rump length were tested by regression analysis. In 25 cases UVBF was measured twice by the same investigator and the intraobserver agreement of these measurements was calculated. Results. A significant increase was evidenced in the gestational age period considered in UV diameter ( r = 0.729, p < 0.0001), TAMXV ( r = 0.691, p < 0.0001) and UVBF ( r = 0.777, p < 0.0001). UVBF increased from 2.26 ml/min at 11 weeks to 15.62 ml/min at 13 + 6 weeks of gestation. The intraobserver ICCs were 0.96, 0.92 and 0.88, respectively, for UV diameter, TAMXV and UVBF. Conclusions. In normal fetuses, UV diameter, TAMVX and flow increase between 11 + 0 and 13 + 6 weeks of gestation. In this gestational age interval, the calculation of UV blood flow and its components shows an intraobserver agreement reliable enough for clinical use. [ABSTRACT FROM AUTHOR]

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%). [ABSTRACT FROM AUTHOR]

Twenty-nine patients with congenital duodenal obstruction (DO) detected as a “double bubble” (DB) on antenatal ultrasound (US) or diagnosed postnatally were seen at the Women's and Children's Hospital between 1985 and 1994; 24 (83%) had antenatal scans, with 21 (87%) DBs visualised. The 3 fetuses with normal scans who developed DO postnatally had duodenal “windsocks”. Five of the 24 scanned patients (21%) were found to have a DB before 20 weeks' gestation: 1 simple duodenal atresia, 2 duodenal atresias with chromosomal abnormalities (1 trisomy 21 and 1 triploidy), 1 biliary atresia with a pre-pyloric vein, and 1 malrotation. Sixteen (67%) cases were detected with scans after 20 weeks (range 28–36 weeks); 12 (75%) of these were done for polyhydramnios. In response to a questionnaire to 9 of the 16 parents whose fetuses underwent a late scan, 5 had had normal early scans elsewhere and 4 did not respond (4 of the remaining 7 had died and 3 were lost to follow-up). Eleven of the 29 patients (38%) had abnormal karyotypes, and 4 (22%) of the 18 with a normal karyotype had associated anomalies. Two sets of familial cases were noted. Early antenatal diagnosis of DO is possible in a minority of cases, and this early diagnosis may be associated with an increased risk of other pathology. Furthermore, early demonstration of a DB at routine US prior to 20 weeks allows appropriate counseling and the option of mid-trimester termination, whereas this is more difficult later in the pregnancy. In all cases detected antenatally, planning of delivery and parent counseling should be achieved. [ABSTRACT FROM AUTHOR]

To assess early embryonic growth and development, 361 pregnancies were studied from 34 to 56 days from last menstrual period. All pregnancies had a subsequent successful outcome. Transvaginal ultrasonography was per formed using an Acuson 128 X P110 with a 5–7.5 MHz probe. Gestational sac diameter, embryonic pole length and embryonic heart rates were measured. Embryonic heart rates were determined by M-mode. Gestational sac diameter, embryonic pole length and embryonic heart rate Increased linearly relative to gestational age and to each other. Regression equations comparing gestational sac diameter and embryonic pole length as well as comparing embryonic heart rate with gestatlonal sac diameter and embryonic pole length were constructed. To he normal, gestations that have (i) sac diameter of 20 mm and 30 mm should contain at least a 2 mm and 5 mm embryo with embryonic heart rates of at least 75 and 100 heats per mm, respectively; and (ii) embryos measurIng 2 mm, 5 mm, 10 mm and 15 mm should display embryonic heart rates of at least 75,100,120 and 130 beats per minute respectively. [ABSTRACT FROM PUBLISHER]

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 < 0.05) and had greater (P < 0.05) gain:feed than control calves. Methionine calves tended (P = 0.06) to have greater apparent total tract NDF and ADF digestibility and lesser (P < 0.05) blood glucose concentration than control and fishmeal calves. These data indicate that maternal methionine supply during the periconception period plays an important role in programming future performance of the offspring. [ABSTRACT FROM AUTHOR]

We present two cases of fetal acrania/exencephaly reconstructed employing the three- (3D) and four-dimensional (4D) HDlive rendering mode in early gestation. Two fetuses with acrania/exencephaly were studied with the 3D/4D HDlive rendering mode at 13 and 15 weeks, respectively. In Case 1, at 13 weeks’ gestation, deformed and degenerated brain tissues were clearly shown using the 3D/4D HDlive rendering mode. In Case 2, at 15 weeks and 6 days of gestation, two amniotic bands and acrania/exencephaly were depicted with the 3D/4D HDlive rendering mode. Fragile brain hemispheres with amniotic bands were rocking with fetal movements. The 3D/4D HDlive rendering mode provides physicians, couples, and their families with important and additional information, and has the potential to supplement two-dimensional and conventional 3D ultrasound in diagnosing fetal acrania/exencephaly. [ABSTRACT FROM AUTHOR]

Early gestation is the critical period for successful establishment of pregnancy and placentation. Numerous factors are associated with altered conceptus growth and pregnancy loss, including maternal nutritional status. To document the patterns of fetal and placental growth, in Study 1, crossbred Angus heifers (n = 16) were estrous synchronized, bred via AI, and ovariohysterectomized at 5-d intervals from d 25 to 90 of gestation. To examine the effects of maternal nutrition, in Study 2, crossbred Angus heifers (n = 27) were synchronized and assigned to 2 dietary intakes at AI (100% of requirements [CON] and 60% of CON [RES]) and were ovariohysterectomized on d 16, 34, or 50 after AI. The gravid uteri were cleaned of adnexa, opened with scissors, blunt dissected, and photographed. A ruler was included in each photo to indicate sizes. Fetal straight crown-rump (C-R) lengths (all days in Study 1 and d 34 and 50 in Study 2) or embryonic disc long axis length (d 16 in Study 2) and surface area of the 2 to 3 largest placentomes (Study 1) were determined by image analysis of the photographs. For Study 1, fetal C-R length increased from 2.2 mm on d 25 to 174.3 mm on d 90, as described by a quadratic equation: y = 0.0223x² + 0.1018x - 16.077 (R² = 0.996, P < 0.01), in which y = fetal C-R length in mm and x = day of gestation. Placentome surface area increased from 91.4 mm² on d 25 to 2,277.9 mm² on d 90, as described by an exponential equation: y = 14.999e0.0546x (R² = 0.903, P < 0.01), in which y = placentome surface area in mm², e = the base of the natural log, and x = day of gestation. For Study 2, on d 16, embryonic disc long axis lengths for CON vs. RES embryos were 1.084 vs. 0.587 mm (SEM 0.396, P = 0.198), and on d 34 and 50, C-R lengths for CON vs. RES were 1.20 and 4.15 vs. 1.17 and 3.79 cm (SEM 0.154 [P = 0.46] and 0.114 [P = 0.12] for d 34 and 50, respectively). These observations will serve as a useful "baseline" for future studies of factors that can affect pregnancy establishment and fetal and placental growth. Additionally, we successfully applied our ovariohysterectomy method to study fetal and placental growth from d 16 to 90 of gestation. Supported by the North Dakota State Board of Agricultural Research and Education, a USDA - National Institute of Food and Agriculture - Agriculture and Food Research Initiative grant (2016-67016-24942), and additional local funds. [ABSTRACT FROM AUTHOR]

Sexual dimorphism is a relevant factor in animal science, since it can affect the gene expression of economically important traits. Eventually, the interest in the prenatal phase in a transcriptome study may not comprise the period of development in which male and female conceptuses are phenotypically divergent. Therefore, it would be interesting if sex differentiation could be performed using transcriptome data, with no need for extra techniques. In this study, the sex of pig conceptuses (embryos at 25 days-old and fetuses at 35 days-old) was determined by reads counts per million (CPM) of Y chromosome-linked genes that were discrepant among samples. Thus, ten genes were used: DDX3Y, KDM5D, ZFY, EIF2S3Y, EIF1AY, LOC110255320, LOC110257894, LOC396706, LOC100625207, and LOC110255257. Conceptuses that presented reads CPM sum for these genes (ΣCPMchrY) greater than 400 were classified as males and those with ΣCPMchrY below 2 were classified as females. It was demonstrated that the sex identification can be performed at early stages of pig development from RNA-sequencing analysis of genes mapped on Y chromosome. Additionally, these results reinforce that sex determination is a mechanism conserved across mammals, highlighting the importance of using pigs as an animal model to study sex determination during human prenatal development. [ABSTRACT FROM AUTHOR]

Objectives were to evaluate circulating progesterone, estrogen, and insulin concentrations in beef heifers during the first 50 d of gestation. We hypothesized that concentrations of progesterone would remain constant during pregnancy while estrogen and insulin would fluctuate during the establishment of pregnancy. To address our hypothesis, crossbred Angus heifers (n = 46), were synchronized, bred via AI and fed to gain 0.22 kg/d. Blood samples were taken via jugular venipuncture on d 16, 22,28, 34,40, and 50 of gestation. Non -bred, non-pregnant control heifers were sampled on d 16 of the estrous cycle. Concentrations of progesterone, estrogen, and insulin in serum were determined using an Immulite 1000 (Siemens, Los Angeles, CA). Statistical analyses were done within PROC MIXED of SAS with day as the variable and cow as a repeated measure. Progesterone was analyzed with a Compound Symmetry covariance structure. Estrogen and insulin were analyzed with a Toeplitz covariance structure. Concentrations of progesterone on d 0 and 50 (1.8 ± 1.8 and 3.6 ± 1.0 ng/mL; respectively) were decreased (P < 0.01) compared with all other days (7.4 ± 0.6 ng/mL). Concentrations of estrogen were similar (P > 0.40) among non-pregnant (42.4 ± 9.0 pg/mL) and pregnant heifers (44.2 ± 3.1 pg/mL). Pregnant heifers had decreased (P < 0.05) concentrations of estrogen on d 16 (36.5 ± 2.5 pg/mL) compared with all other days (45.7 ± 3.2 pg/mL). Concentrations of estrogen were greater (P < 0.05) on d 40 (50.5 ± 3.6 pg/mL), compared with d 28 and 50 (42.7 ± 2.7 and 43.9 ± 3.9 pg/mL; respectively). Concentrations of estrogen tended (P = 0.07) to be decreased on d 22 vs. d 40 (44.4 ± 2.7 vs. 50.5 ± 3.6 pg/mL; respectively). There was also a tendency (P = 0.08) for estrogen to be reduced on d 28 (42.7 ± 2.7 pg/mL) compared with d 50 (43.9 ± 3.9 pg/mL). Concentrations of insulin were not different (P = 0.53) among pregnancy status or days of gestation. In conclusion, concentrations of progesterone in non-pregnant heifers were less than those of pregnant heifers until d 50 post-breeding, and estrogen but not insulin was differentially observed through the early gestational period. [ABSTRACT FROM AUTHOR]

The ability to diagnosis and identify successful pregnancies early in gestation has important economic and management applications for cattle producers. Currently, producers are essentially limited to d 30 of gestation as the earliest time point for pregnancy diagnosis due to the effectiveness of most ultrasound and chemical based methods. Pregnancy associated glycoproteins (PAG) are produced by the ruminant placenta and can be used to accurately detect pregnancy as early as d 28 of gestation using commercially available tests. Recent data from our lab suggests pregnancy status can be determined by PAG as early as d 24. Data also indicates that circulating PAGs may be a marker of embryonic viability and predictive of embryonic mortality. The objective of the current study was to determine if early gestation circulating PAG levels could be used to predict heifers likely to maintain pregnancy. Our hypothesis was Day 24 PAG levels could be predictive of pregnancy maintenance until d 60 if a threshold PAG level was achieved. In vitro produced embryos were transferred into synchronized virgin, predominantly Holstein heifers (n = 226) using timed embryo transfer (TET). Blood was collected at d 24 for PAG analysis as well as d 31 for confirmation of pregnancy. Final pregnancy confirmation occurred on d 60 via transrectal ultrasound. Serum concentrations of PAG were quantified using an in house PAG ELISA with antibodies raised against PAGs expressed early in gestation. Following TET, there were 134 heifers identified pregnant on d 31 of gestation (59%) using ultrasound and PAG testing. Only heifers that were pregnant at d 31 were analyzed in this study. Between d 31 and 60, 25 heifers experienced pregnancy loss. Circulating concentrations of PAG were significantly higher (P < 0.05) at d 24 of gestation in heifers that maintained pregnancy until d 60 (n = 109; 2.82 ± 0.22 ng/mL) than heifers that lost pregnancy between d 31 and 60 (n = 25; 0.737 ± 0.166 ng/mL). However, a receiver operating characteristic (ROC) curve was inconclusive at identifying a predictive cutoff value for diagnosing pregnancy, likely due to the specific antibody's specificity. In summary, early gestation circulating PAG concentration may have application in predicting embryo loss in heifers; however, sensitivity and specificity of current assays should be refined for this purpose. [ABSTRACT FROM AUTHOR]

The ability to diagnosis and identify successful pregnancies early in gestation has important economic and management applications for cattle producers. Currently, producers are essentially limited to d 30 of gestation as the earliest time point for pregnancy diagnosis due to the effectiveness of most ultrasound and chemical based methods. Pregnancy associated glycoproteins (PAG) are produced by the ruminant placenta and can be used to accurately detect pregnancy as early as d 28 of gestation using commercially available tests. Recent data from our lab suggests pregnancy status can be determined by PAG as early as d 24. Data also indicates that circulating PAGs may be a marker of embryonic viability and predictive of embryonic mortality. The objective of the current study was to determine if early gestation circulating PAG levels could be used to predict heifers likely to maintain pregnancy. Our hypothesis was Day 24 PAG levels could be predictive of pregnancy maintenance until d 60 if a threshold PAG level was achieved. In vitro produced embryos were transferred into synchronized virgin, predominantly Holstein heifers (n = 226) using timed embryo transfer (TET). Blood was collected at d 24 for PAG analysis as well as d 31 for confirmation of pregnancy. Final pregnancy confirmation occurred on d 60 via transrectal ultrasound. Serum concentrations of PAG were quantified using an in house PAG ELISA with antibodies raised against PAGs expressed early in gestation. Following TET, there were 134 heifers identified pregnant on d 31 of gestation (59%) using ultrasound and PAG testing. Only heifers that were pregnant at d 31 were analyzed in this study. Between d 31 and 60, 25 heifers experienced pregnancy loss. Circulating concentrations of PAG were significantly higher (P < 0.05) at d 24 of gestation in heifers that maintained pregnancy until d 60 (n = 109; 2.82 ± 0.22 ng/mL) than heifers that lost pregnancy between d 31 and 60 (n = 25; 0.737 ± 0.166 ng/mL). However, a receiver operating characteristic (ROC) curve was inconclusive at identifying a predictive cutoff value for diagnosing pregnancy, likely due to the specific antibody's specificity. In summary, early gestation circulating PAG concentration may have application in predicting embryo loss in heifers; however, sensitivity and specificity of current assays should be refined for this purpose. [ABSTRACT FROM AUTHOR]

The time period from conception through the embryonic stage of development is critical in terms of establishment, recognition, and maintenance of pregnancy to term. Research on factors influencing embryonic development up to d 14 is relatively simple. Much less is known about the influences on conceptus (embryo and membranes) development from the time embryo flushing becomes impossible to the end of the embryonic stage (~d 16 to d 50 in bovine). To access this critical period we developed and optimized a standing flank hysterectomy procedure. Protocols for ovariectomy and cesarean section from veterinary medicine and research practices were combined and modified, resulting in the technique described herein. Briefly, heifers were placed in a cattle restraining chute and immobilized, administered local anesthetic into the left paralumbar fossa, and given an epidural nerve block. A vertical 18 to 25 cm incision was then made through the skin, muscle layers, and peritoneum into the peritoneal cavity via either blunt dissection or incision. Centauri knots were placed on the right and left uterine arteries, the right and left ovarian spiral arteries, and around the body of the uterus just cranial to the cervix and on the cranial end of cervix. Uterine/ovarian tissue was separated from the broad ligament and incised cranially from ligatures to include as much uterine body as possible. To optimize the procedure Angus crossbred heifers (n =46; ~ 15 mo of age; BW = 362.3 ± 34.7 kg) were synchronized, bred via AI, and hysterectomized on d 16, 22, 28, 34, 40, or 50 of gestation or not bred (NP) and hysterectomized on d 16 of the estrous cycle. There was a strong negative correlation (r = -0.53, P = 0.0009) between time required for surgical procedure and progression of surgical optimization. Surgery time was least (P = 0.04) in NP controls (69.0 ± 20.8 min). Surgery times were also influenced by stage of gestation (P = 0.04). In pregnant animals, time decreased from d 22 (120.0 ± 12.0 min) to d 40 (79.5 ± 12.0 min); then increased at d 50 (90.5 ± 14.7 min). All heifers fully recovered, were placed on feed, and performed well in the feedlot(l.99 kg/dADG; 13.77 DMI; 0.145 G:F; 2% Select, 71% Choice, and 27% Prime). This technique offers a plethora of opportunities to explore factors related to pregnancy success and document embryo and placental development in detail. [ABSTRACT FROM AUTHOR]