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Introduction: Recent research indicates an important role in the placental fetal brain axis, with a paucity of information reported in large animals. Melatonin supplementation has been investigated as a potential therapeutic to negate fetal growth restriction. We hypothesized that maternal nutrient restriction and melatonin supplementation would alter neurotransmitter pathways in fetal blood, cotyledonary and hypothalamus tissue., Methods: On day 160 of gestation, Brangus heifers (n = 29 in fall study; n = 25 in summer study) were assigned to one of four treatments: adequately fed (ADQ-CON; 100% NRC recommendation), nutrient restricted (RES-CON; 60% NRC recommendation), and ADQ or RES supplemented with 20 mg/d of melatonin (ADQ-MEL; RES-MEL). Placentomes, fetal blood, and hypothalamic tissue were collected at day 240 of gestation. Neurotransmitters were analyzed in fetal blood and fetal and placental tissues. Transcript abundance of genes in the serotonin pathway and catecholamine pathway were determined in fetal hypothalamus and placental cotyledon., Results: Serotonin was increased (P < 0.05) by 12.5-fold in the blood of fetuses from RES dams versus ADQ in the fall study. Additionally, melatonin supplementation increased (P < 0.05) neurotransmitter metabolites and transcript abundance of the monoamine oxidase A (MAOA) enzyme in the cotyledon. In the summer study, plasma dopamine and placental dopamine receptors were decreased (P < 0.05) in RES dams versus ADQ., Discussion: In conclusion, these data indicate novel evidence of the presence of neurotransmitters and their synthesis and metabolism in the bovine conceptus, which could have greater implications in establishing postnatal behavior., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Prenatal development is reliant on a functioning placenta, which can be influenced by maternal nutrition. Moreover, the variation in cotyledonary capacity within an animal has not been fully examined to date. Therefore, the purpose of this study was to determine the effect of (1) placentome size and (2) maternal nutrient restriction on molecular, microscopic, and macroscopic features of bovine placentomes during late gestation., Methods: Pregnant cows (n = 6) were placed into one of 2 treatments: CON (100% NRC) vs RES (60% of NRC) from day 140 until slaughter at day 240 of gestation. Placentomes of various sizes were perfused to assess macroscopic blood vessel density of the cotyledon. Microscopic imaging and RNA extraction for sequencing was performed., Results: Macroscopic blood vessel density relative to placentome weight was not different (P = 0.42) among small, medium, or large placentomes. Cotyledonary microscopic blood vessel number, area, and perimeter was increased (P < 0.005) in high versus low blood perfusion areas. Differential expressed gene (DEG) analysis showed 209 upregulations and 168 downregulations in the RES group (P ≤ 0.0001). Gene Ontology (GO) analysis showed that downregulated enriched terms were involved in blood vessel and mesenchymal stem cells development, whereas upregulated enriched terms were involved with translation and ribosomal function., Discussion: This study demonstrates that placentome function is uniform across various placentome sizes within an animal. However, microscopic heterogeneity exists within each placentome. Maternal nutrient constraints alter placental transcriptomics which may yield compensatory mechanisms involved in nutrient transport including increased perimeter., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Recent research has shown expression of clock genes in peripheral tissue explants, targeting multiple pathways leading to the entrainment of circadian rhythms. Temporal variations are not solely regulated by photoperiod, but factors such as maternal feed availability can entrain fetal circadian clock. Currently, a paucity of information exists for clock gene expression and short-term temporal transcript abundance in the bovine placenta, which is essential for proper offspring development. Therefore, the objective of this study was to determine the effect of early to mid-gestational nutrient restriction on clock genes, angiogenic factors, and nutrient sensing genes mRNA transcript abundance in placental explants during a 24 h period. Placentomes from adequately fed and nutrient restricted heifers were collected via Cesarean section at day 180 of gestation; separated into caruncular and cotyledonary tissue and placed in culture media for a 24 h period. The mRNA transcript abundance of clock genes (ARNTL, CRY1, and PER2), angiogenic factors (HIF1A and VEGFA), and nutrient sensing genes (NAMPT and NR3C1) was determined every 4 h. Clock genes were expressed in caruncular and cotyledonary explant tissue. The caruncular explant transcript abundance of the clock genes was not influenced by time (P > 0.05); while ARNTL abundance decreased over time in the cotyledon explant (P < 0.05). A main effect of time was observed for HIF1A, VEGFA, and NR3C1 in the caruncular tissue (P < 0.05). Although, angiogenic factors and nutrient sensing genes in cotyledonary tissue displayed evident temporal variation in transcript abundance (P < 0.05). Nutrient restriction did not alter (P > 0.15) mRNA transcript abundance of clock genes, angiogenic factors, or nutrient sensing genes in either caruncular or cotyledonary tissue. Interestingly, these data may indicate limited transmission and synchronization of maternal and fetal temporal variations in transcript abundance. These findings demonstrate that multiple timepoint collections are needed in future studies due to the innate existence of temporal oscillations observed in the bovine placenta., Competing Interests: Declaration of competing interest The authors declare that there is not an existent conflict of interest in this research., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The objective was to determine the effects of pregnancy status on oxylipin profiles and eicosanoid metabolizing enzymes and in corpora lutea (CL) or endometrial (caruncle; CAR and intercaruncle; IC) tissues. Angus crossed cattle were synchronized with the CO-Synch protocol and artificially inseminated (AI). Sixteen days after AI, cattle were euthanized, and reproductive tracts collected from 6 non-pregnant and 6 pregnant cows. Oxylipin profiles and concentrations of progesterone (P 4 ) were obtained from CL tissues. The activity of cytochrome P450 1A (CYP1A) and UDP-glucuronosyltransferase (UGT) enzymes were determined using specific luminogenic substrates. Data were analyzed using the MIXED procedure of SAS, and the model included pregnancy status. Corpora lutea of pregnant cattle contained greater (P < 0.05) concentrations of 9,10-DiHODE, 15,16-DiHODE, and 9,10-DiHOME. These oxylipins have been observed to increase cellular proliferation and vasodilation. Activity of CYP1A in the CL and UGT in CAR and IC was not different (P > 0.05) between pregnant and non-pregnant cattle. In the CL, activity of UGT was decreased (P < 0.05) in pregnant vs. non-pregnant cattle. The decrease in CL UGT activity during pregnancy indicates alterations in local hormone metabolism, while no differences in CL weight nor amount of P 4 in CL were different between pregnant and non-pregnant cattle. Moreover, the increase in specific concentrations of oxylipins in the CL may indicate a novel pathway of steroid and eicosanoid metabolism during maternal recognition of pregnancy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The objective of the present study was to evaluate the effects of beef heifer development practices and the influence of season on uterine artery hemodynamics during mid to late gestation. Metrics of uterine artery blood flow (BF) of fall calving and spring calving crossbred beef heifers (n = 27) developed on either a low-input (LOW|FALL n = 6; LOW|SPRING n = 6) or a conventional (CON|FALL n = 9; CON|SPRING n = 6) heifer development scheme were evaluated. Heifer body weight (BW) was measured every 30 days, and uterine BF, arterial diameter (AD), pulsatility index (PI), and resistance index were measured for uterine arteries ipsilateral and contralateral to the conceptus on days 180, 210, and 240 of gestation. Calf birth weight was assessed at parturition. Repeated-measures ANOVA was performed. There were significant treatment × season (P = 0.0001) and season × day (P = 0.003) interactions on heifer BW. Main effects of season (P = 0.04) and gestational day (P = 0.0001) were observed on contralateral BF, and there was a season × day interaction (P = 0.03) on ipsilateral BF. As such, there was a season × day interaction on total blood flow (TBF; P = 0.05), whereby TBF increased as gestation progressed and spring calving heifers displayed increased TBF. However, when adjusted for BW, an additional main effect of treatment was observed (P = 0.0007) in which LOW heifers had increased TBF compared with CON heifers. Correspondingly, LOW heifers displayed increased AD compared with CON heifers, and spring calving heifers had greater AD than fall calving females. There was also a main effect of season on calf birth weight (P = 0.02). It was concluded that developing replacement heifers with low-input management schemes does not yield compromised uteroplacental hemodynamics compared with traditionally developed females when nutrition during gestation is adequate. Furthermore, spring calving 2-year-old heifers have increased uteroplacental BF compared with their fall calving counterparts. Our results imply that producers who seek to decrease development costs by feeding replacements to lighter target breeding weights may do so without compromising mid to late gestation uterine BF when heifers are not nutrient restricted during pregnancy., (Copyright © 2016 Elsevier Inc. All rights reserved.)