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Endometrial-derived uterine histotroph is a critical component of nutrient supply to a growing conceptus throughout gestation; however, the effect of nutritional plane on histotroph nutrient composition remains unknown in multiparous cows. We hypothesized that differing planes of nutrition would alter histotroph and serum nutrient composition in beef cattle. Thus, we evaluated serum and histotroph amino acid and glucose composition, and serum non-esterified fatty acids (NEFA) and blood urea nitrogen (BUN) in cows individually fed to maintain body weight (BW; 0 kd/d, n = 9; CON) compared with those losing moderate BW (-0.7 kg/d, n = 9; NEG). After 49 d of differing nutritional planes, cows were subjected to the 7-d CoSynch + controlled internal drug release device estrus synchronization protocol and then slaughtered on day 62. Blood serum (days 0 and 62) and uterine histotroph [day 62; from uterine horns ipsilateral and contralateral to the corpus luteum (CL)] were collected and analyzed for concentrations of amino acids, glucose, and NEFA. Performance characteristics, body composition via ultrasound (days 0 and 62), and carcass characteristics were collected. Body condition score, change in BW, average daily gain, dry matter intake, and gain:feed were decreased (P ≤ 0.05) in NEG vs. CON cows. There were no differences in body composition or carcass characteristics, except an increase (P ≤ 0.05) in dressing percentage in NEG cows due to differences in gut fill, consistent with study design. Serum NEFA increased (P ≤ 0.05) in the NEG group, but there were no differences between NEG vs. CON in glucose or BUN. Serum histidine increased (P ≤ 0.05) and alanine, isoleucine, and tryptophan decreased (P ≤ 0.05) in NEG vs. CON cows. Compared with that of the uterine horn ipsilateral to the CL, histotroph from the uterine horn contralateral to the CL had increased (P ≤ 0.05) isoleucine, asparagine, and proline concentrations in NEG cows, and decreased (P ≤ 0.05) tryptophan as a proportion of essential and total amino acids. There were no differences in glucose concentrations of histotroph contralateral or ipsilateral to the CL. Cow nutritional plane does alter serum and histotroph amino acid composition, although the presence of an embryo may be necessary to fully elucidate these changes. Differences in serum and histotroph tryptophan should be given consideration in future studies due to its importance as an essential amino acid in protein synthesis and bioactive affects., (© 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.)

The objective of this study was to determine the dose-dependent response of one-carbon metabolite (OCM: methionine, choline, folate, and vitamin B12) supplementation on heifer dry matter intake on fixed gain, organ mass, hematology, cytokine concentration, pancreatic and jejunal enzyme activity, and muscle hydrogen peroxide production. Angus heifers (n = 30; body weight [BW] = 392.6 ± 12.6 kg) were individually fed and assigned to one of five treatments: 0XNEG: total mixed ration (TMR) and saline injections at days 0 and 7 of the estrous cycle, 0XPOS: TMR, rumen-protected methionine (MET) fed at 0.08% of the diet dry matter, rumen-protected choline (CHOL) fed at 60 g/d, and saline injections at days 0 and 7, 0.5X: TMR, MET, CHOL, 5-mg B12, and 80-mg folate injections at days 0 and 7, 1X: TMR, MET CHOL, 10-mg vitamin B12, and 160-mg folate at days 0 and 7, and 2X: TMR, MET, CHOL, 20-mg vitamin B12, and 320-mg folate at days 0 and 7. All heifers were estrus synchronized but not bred, and blood samples were collected on days 0, 7, and at slaughter (day 14) during which tissues were collected. By design, heifer ADG did not differ (P = 0.96). Spleen weight and uterine weight were affected cubically (P = 0.03) decreasing from 0XPOS to 0.5X. Ovarian weight decreased linearly (P < 0.01) with increasing folate and B12 injection. Hemoglobin and hematocrit percentage were decreased (P < 0.01) in the 0.5X treatment compared with all other treatments. Plasma glucose, histotroph protein, and pancreatic α-amylase were decreased (P ≤ 0.04) in the 0.5X treatment. Heifers on the 2X treatment had greater pancreatic α-amylase compared with 0XNEG and 0.5X treatment. Interleukin-6 in plasma tended (P = 0.08) to be greater in the 0XPOS heifers compared with all other treatments. Lastly, 0XPOS-treated heifers had reduced (P ≤ 0.07) hydrogen peroxide production in muscle compared with 0XNEG heifers. These data imply that while certain doses of OCM do not improve whole animal physiology, OCM supplementation doses that disrupt one-carbon metabolism, such as that of the 0.5X treatment, can induce a negative systemic response that results in negative effects in both the dam and the conceptus during early gestation. Therefore, it is necessary to simultaneously establish an optimal OCM dose that increases circulating concentrations for use by the dam and the conceptus, while avoiding potential negative side effects of a disruptive OCM, to evaluate the long-term impacts of OCM supplementation of offspring programming., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Objectives of this study were to determine effects of exogenous progesterone (via controlled internal drug releasing devices; CIDR) in combination with exogenous gonadotropins (PMSG/hCG) use either at CIDR removal or 1 d before CIDR removal to induce estrus and cyclicity and subsequently enhance the proportion of ewes lambing, lambing rate, prolificacy, and days to lambing in ewes bred out of season. Multiparous ewes ( n = 414) were randomly assigned to one of four treatments: untreated ( U , n = 122), 7 d CIDR ( C , n = 97), 7 d CIDR plus P.G. 600 (240 IU pregnant mare serum gonadotropin [PMSG] and 120 IU human chorionic gonadotropin [hCG]) at CIDR removal ( CPG0 , n = 97), and 7 d CIDR plus P.G. 600 (240 IU PMSG and 120 IU hCG) 1 d before CIDR removal ( CPG-1 , n = 98). Rams ( n = 15) were joined with ewes immediately after CIDR removal and remained with ewes for a 21 d breeding period. Lambing data were summarized for the first 10 days of the lambing season and overall. Categorical data were analyzed using the GLIMMIX procedure of SAS whereas non-categorical data were analyzed using the mixed procedure. Proportion of ewes lambing in the first 10 d was greater ( P < 0.05) for CPG0 and CPG-1 ewes compared with C ewes, which was greater ( P < 0.0001) compared with U ewes. Overall proportion of ewes lambing was greater ( P ≤ 0.0001) in all treatments utilizing CIDR compared with U ewes, but no differences ( P ≥ 0.84) due to P.G. 600 were detected compared with C. Lambing rate in the first 10 d was greater ( P < 0.05) for CPG-1 than C, with CPGO being intermediate, and all CIDR-treated ewes being greater than U ( P < 0.0001). Overall lambing rate increased ( P ≤ 0.0001) in all treatments utilizing CIDR compared with U ewes, but no differences ( P ≥ 0.76) due to P.G. 600 were detected compared with C. Prolificacy was similar among all treatments both for the first 10 d of the lambing season ( P = 0.86) and overall ( P = 0.80). Day of lambing in the lambing season was reduced ( P ≤ 0.03) for CPG0 and CPG-1 compared with CIDR-treated ewes, which was reduced ( P < 0.0001) compared with U ewes (days 10.6, 9.0, 13.4, and 24.4 ± 0.9 for CPG0, CPG-1, CON, and U, respectively). Though timing of P.G. 600 did not influence results, the combination of CIDR and P.G. 600 enhanced the proportion of lambs born earlier in the lambing season, and incorporating a CIDR with or without P.G. 600 enhanced the overall proportion of ewes lambing and lambing rate in out-of-season breeding scenarios., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Herein, we present a dataset based on the RNA-Seq analysis of liver tissue from bovine female fetuses at day 83 of gestation. The findings were reported in the main article, "Periconceptual maternal nutrition affects fetal liver programming of energy- and lipid-related genes" [1]. These data were generated to investigate the effects of periconceptual maternal vitamin and mineral supplementation and rates of body weight gain on the transcript abundance of genes associated with fetal hepatic metabolism and function. To this end, crossbred Angus beef heifers ( n  = 35) were randomly assigned to 1 of 4 treatments in a 2 × 2 factorial design. The main effects tested were vitamin and mineral supplementation (VTM or NoVTM - at least 71 days pre-breeding to day 83 of gestation) and rate of weight gain (low (LG - 0.28 kg/d) or moderate (MG - 0.79 kg/d) - from breeding to day 83). The fetal liver was collected on day 83 ± 0.27 of gestation. After total RNA isolation and quality control, strand-specific RNA libraries were prepared and sequenced on the Illumina® NovaSeq 6000 platform to generate paired-end 150-bp reads. After read mapping and counting, differential expression analysis was performed with edgeR. We identified 591 unique differentially expressed genes across all six vitamin-gain contrasts (FDR ≤ 0.1). To our knowledge, this is the first dataset investigating the fetal liver transcriptome in response to periconceptual maternal vitamin and mineral supplementation and/or the rate of weight gain. The data described in this article provides genes and molecular pathways differentially programming liver development and function., Competing Interests: Authors J. C. Forcherio and R. Scott are employees of Purina Animal Nutrition LLC (Land O'Lakes, Inc., Arden Hills, MN, USA), which sponsored the sample analysis for this experiment. Purina Animal Nutrition LLC manufactured the Purina® Wind & Rain® Storm® AllSeason 7.5 Complete mineral, the VTM and NoVTM pellets, and the protein/energy supplement used in this study. The funders had no role in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results that were done entirely independently by North Dakota State University and Auburn University personnel. All the other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

During pregnancy, the fetus relies on the dam for its nutrient supply. Nutritional stimuli during fetal organ development can program hepatic metabolism and function. Herein, we investigated the role of vitamin and mineral supplementation (VTM or NoVTM-at least 71 days pre-breeding to day 83 of gestation) and rate of weight gain (low (LG) or moderate (MG)-from breeding to day 83) on the fetal liver transcriptome and the underlying biological pathways. Crossbred Angus beef heifers ( n = 35) were randomly assigned to one of four treatments in a 2 × 2 factorial design (VTM&#95;LG, VTM&#95;MG, NoVTM&#95;LG, and NoVTM&#95;MG). Gene expression was measured with RNA-Seq in fetal livers collected on day 83 ± 0.27 of gestation. Our results show that vitamin and mineral supplementation and rate of weight gain led to the differential expression of hepatic genes in all treatments. We identified 591 unique differentially expressed genes across all six VTM-gain contrasts (FDR ≤ 0.1). Over-represented pathways were related to energy metabolism, including PPAR and PI3K-Akt signaling pathways, as well as lipid metabolism, mineral transport, and amino acid transport. Our findings suggest that periconceptual maternal nutrition affects fetal hepatic function through altered expression of energy- and lipid-related genes.

Herein, we evaluated the hepatic lipid metabolic profiles of bovine fetuses in response to maternal vitamin and mineral supplementation (VMSUP; supplemented (VTM) or not (NoVTM)) and two different rates of gain (GAIN; low gain (LG), 0.28 kg/d, or moderate gain (MG), 0.79 kg/d). Crossbred Angus heifers ( n = 35; initial BW = 359.5 ± 7.1 kg) were randomly assigned to a 2 × 2 factorial arrangement, resulting in the following treatment combinations: NoVTM-LG ( n = 9), NoVTM-MG ( n = 9), VTM-LG ( n = 9), and VTM-MG ( n = 8). Heifers received their treatments until d 83 of gestation, when they were ovariohysterectomized. Fetuses were harvested and liver samples were analyzed via ultrahigh-performance liquid chromatography-tandem mass spectroscopy to characterize lipid profiles and abundances. We identified 374 biochemicals/metabolites belonging to 57 sub-pathways of the lipid metabolism super-pathway. The majority of the biochemicals/metabolites ( n = 152) were significantly affected by the main effect of GAIN. Maternal moderate rates of gain resulted in greater abundances ( p ≤ 0.0001) of ω-3 fatty acids (eicosapentaenoate, docosapentaenoate, and docosahexaenoate) and lower abundances ( p ≤ 0.0001) of ω-6 fatty acids. Further, MG resulted in the accumulation of several diacylglycerols and depletion of the majority of the monoacylglycerols. Concentrations of nearly all acylcarnitines ( p ≤ 0.03) were decreased in VTM-LG fetal livers compared to all other treatment combinations, indicating a greater rate of complete oxidation of fatty acids. Levels of secondary bile acids were impacted by VMSUP, being greater ( p ≤ 0.0048) in NoVTM than in VTM fetal livers. Moreover, NoVTM combined with lower rate of gain resulted in greater concentrations of most secondary bile acid biochemicals/metabolites. These data indicate that maternal diet influenced and altered fetal hepatic lipid composition in the first trimester of gestation. Maternal body weight gain exerted a greater influence on fetal lipid profiles than vitamin and mineral supplementation. Specifically, lower rate of gain (0.28 kg/d) resulted in an increased abundance of the majority of the biochemicals/metabolites identified in this study.

Adequate maternal nutrition is key for proper fetal development and epigenetic programming. One-carbon metabolites (OCM), including vitamin B12, folate, choline, and methionine, play a role in epigenetic mechanisms associated with developmental programming. This study investigated the presence of B12 and folate in maternal serum, allantoic fluid (ALF), and amniotic fluid (AMF), as well as how those concentrations in all three fluids correlate to the concentrations of methionine-folate cycle intermediates in heifers receiving either a control (CON) or restricted (RES) diet for the first 50 d of gestation and fetal hepatic gene expression for methionine-folate cycle enzymes. Angus cross heifers (n = 43) were estrus synchronized, bred via artificial insemination with semen from a single sire, and randomly assigned to one of two nutrition treatments (CON = 20, RES = 23). Heifers were ovariohysterectomized on either day 16 (n = 14), 34 (n = 15), or 50 of gestation (n = 14), where samples of maternal serum (n = 42), ALF (n = 29), and AMF (n = 11) were collected and analyzed for concentrations of folate and B12. Concentrations of B12 and folate in ALF were greater (P < 0.05) in RES compared to CON. For ALF, folate concentrations were also greater (P < 0.01) on day 34 compared to day 50. There was a significant (P = 0.04) nutrition × fluid interaction for B12 concentrations where concentrations were greatest in restricted ALF, intermediate in control ALF, and lowest in CON and RES serum and AMF. Folate concentrations were greatest (P < 0.01) in ALF, intermediate in serum, and lowest in AMF. Additionally, positive correlations (P < 0.05) were found between ALF and AMF folate concentrations and AMF concentrations of methionine, serine, and glycine. Negative correlations (P < 0.05) between AMF folate and serum homocysteine were also observed. Both positive and negative correlations (P < 0.05) depending on the fluid evaluated were found between B12 and methionine, serine, and glycine concentrations. There was a downregulation (P = 0.05) of dihydrofolate reductase and upregulation (P = 0.03) of arginine methyltransferase 7 gene expression in RES fetal liver samples compared with CON fetal liver on day 50. Combined, these data show restricted maternal nutrition results in increased B12 and folate concentrations present in fetal fluids, and increased expression of genes for enzymes within one-carbon metabolism., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We evaluated the effects of vitamin and mineral supplementation (from pre-breeding to day 83 of gestation) and two rates of gain (from breeding to day 83 of gestation) on trace mineral concentrations in maternal and fetal liver, fetal muscle, and allantoic (ALF) and amniotic (AMF) fluids. Crossbred Angus heifers (n = 35; BW = 359.5 ± 7.1 kg) were randomly assigned to one of two vitamin and mineral supplementation treatments (VMSUP; supplemented (VTM) vs. unsupplemented (NoVTM)). The VMSUP factor was initiated 71 to 148 d before artificial insemination (AI), allowing time for the mineral status of heifers to be altered in advance of breeding. The VTM supplement (113 g·heifer−1·d−1) provided macro and trace minerals and vitamins A, D, and E to meet 110% of the requirements specified by the NASEM, and the NoVTM supplement was a pelleted product fed at a 0.45 kg·heifer−1·day−1 with no added vitamin and mineral supplement. At AI, heifers were assigned to one of two rates of gain treatments (GAIN; low gain (LG) 0.28 kg/d or moderate gain (MG) 0.79 kg/d) within their respective VMSUP groups. On d 83 of gestation fetal liver, fetal muscle, ALF, and AMF were collected. Liver biopsies were performed prior to VMSUP factor initiation, at the time of AI, and at the time of ovariohysterectomy. Samples were analyzed for concentrations of Se, Cu, Zn, Mo, Mn, and Co. A VMSUP × GAIN × day interaction was present for Se and Cu (p < 0.01 and p = 0.02, respectively), with concentrations for heifers receiving VTM being greater at AI and tissue collection compared with heifers not receiving VTM (p < 0.01). A VMSUP × day interaction (p = 0.01) was present for Co, with greater (p < 0.01) concentrations for VTM than NoVTM at the time of breeding. VTM-MG heifers had greater concentrations of Mn than all other treatments (VMSUP × GAIN, p < 0.01). Mo was greater (p = 0.04) for MG than LG, while Zn concentrations decreased throughout the experiment (p < 0.01). Concentrations of Se (p < 0.01), Cu (p = 0.01), Mn (p = 0.04), and Co (p = 0.01) were greater in fetal liver from VTM than NoVTM. Mo (p ≤ 0.04) and Co (p < 0.01) were affected by GAIN, with greater concentrations in fetal liver from LG than MG. In fetal muscle, Se (p = 0.02) and Zn (p < 0.01) were greater for VTM than NoVTM. Additionally, Zn in fetal muscle was affected by GAIN (p < 0.01), with greater concentrations in LG than MG. The ALF in VTM heifers (p < 0.01) had greater Se and Co than NoVTM. In AMF, trace mineral concentrations were not affected (p ≥ 0.13) by VMSUP, GAIN, or their interaction. Collectively, these data suggest that maternal nutrition pre-breeding and in the first trimester of gestation affects fetal reserves of some trace minerals, which may have long-lasting impacts on offspring performance and health.

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.

Thirty-five crossbred Angus heifers (initial BW = 359.5 ± 7.1 kg) were randomly assigned to a 2 × 2 factorial design to evaluate effects of vitamin and mineral supplementation [VMSUP; supplemented (VTM) vs. unsupplemented (NoVTM)] and different rates of gain [GAIN; low gain (LG), 0.28 kg/d, vs. moderate gain (MG), 0.79 kg/d] during the first 83 d of gestation on dam hormone and metabolic status, fetal tissue and organ mass, and concentration of glucose and fructose in fetal fluids. The VMSUP was initiated 71 to 148 d before artificial insemination (AI), allowing time for mineral status of heifers to be altered in advance of breeding. At AI heifers were assigned their GAIN treatment. Heifers received treatments until the time of ovariohysterectomy (d 83 ± 0.27 after AI). Throughout the experiment, serum samples were collected and analyzed for non-esterified fatty acids (NEFA), progesterone (P4), insulin, and insulin-like growth factor 1 (IGF-1). At ovariohysterectomy, gravid reproductive tracts were collected, measurements were taken, samples of allantoic (ALF) and amniotic (AMF) fluids were collected, and fetuses were dissected. By design, MG had greater ADG compared to LG (0.85 vs. 0.34 ± 0.04 kg/d, respectively; p < 0.01). Concentrations of NEFA were greater for LG than MG (p = 0.04) and were affected by a VMSUP × day interaction (p < 0.01), with greater concentrations for NoVTM on d 83. Insulin was greater for NoVTM than VTM (p = 0.01). A GAIN × day interaction (p < 0.01) was observed for IGF-1, with greater concentrations for MG on d 83. At d 83, P4 concentrations were greater for MG than LG (GAIN × day, p < 0.01), and MG had greater (p < 0.01) corpus luteum weights versus LG. Even though fetal BW was not affected (p ≥ 0.27), MG fetuses had heavier (p = 0.01) femurs than LG, and VTM fetuses had heavier (p = 0.05) livers than those from NoVTM. Additionally, fetal liver as a percentage of BW was greater in fetuses from VTM (P = 0.05; 3.96 ± 0.06% BW) than NoVTM (3.79 ± 0.06% BW), and from LG (p = 0.04; 3.96 ± 0.06% BW) than MG (3.78 ± 0.06% BW). A VMSUP × GAIN interaction was observed for fetal small intestinal weight (p = 0.03), with VTM-MG being heavier than VTM-LG. Therefore, replacement heifer nutrition during early gestation can alter the development of organs that are relevant for future offspring performance. These data imply that compensatory mechanisms are in place in the developing conceptus that can alter the growth rate of key metabolic organs possibly in an attempt to increase or decrease energy utilization.

The cotyledon and caruncle tissues provide a functional bridge between the fetus and the dam. However, the relationship between these tissues and the transcriptomic profile that underlies the tissue functions remains elusive. Herein we investigate the expression profile of cotyledon and caruncle from nulliparous beef heifers carrying female fetuses at day 83 of pregnancy to identify changes occurring across tissues that contribute to placental function and their tissue-specific roles. We identified 2654 differentially expressed genes [padj ≤ 0.05, abs(log2FC) ≥ 1], including nutrient transporters and paternally imprinted genes. We found key regulators of tissue function and differentiation, including FOXO4, GATA2, GATA3, and HAND1, rewired between the tissues. Finally, we shed light on the over-represented pathways related to immune tolerance, tissue differentiation and remodeling. Our findings highlighted the intricate and coordinated cross-talk between fetal-maternal tissues. They provided evidence of a fine-tuned gene regulatory network underlying pregnancy and tissue-specific function in the bovine placenta., (Published by Elsevier Inc.)

Multiparous Rambouillet ewes (n = 32) were allocated in a completely randomized design to determine if rumen-protected L-arginine (RP-Arg) supplementation during mid- and late gestation would 1) alter maternal carotid artery hemodynamics and 2) affect circulating amino acids associated with arginine metabolism in dams from day 54 of gestation to parturition and in their offspring from birth to 54 d of age. Ewes were assigned to one of three treatments from day 54 ± 3.9 to parturition: control (CON; 100% nutrient requirements), restricted (RES; 60% of CON), and RES plus 180 mg RP-Arg•kg BW-1•d1 (RES-ARG). Ewes were penned individually in a temperature-controlled facility. Carotid artery hemodynamics was measured via Doppler ultrasound at day 50 and 130 of gestation. Maternal serum was collected at day 54 and 138 of gestation and at parturition. At parturition, lambs were immediately removed from their dams and reared independently. Lamb serum samples were collected at birth and 1, 3, 7, 33, and 54 d of age. Pulsatility index was the only hemodynamic measurement altered by dietary treatment, where day 130 measurements were greater (P ≤ 0.04) for RES and RES-ARG compared with CON. The change in pulsatility index was greater (P < 0.01) for RES compared with CON but tended to be intermediate (P ≥ 0.12) for RES-ARG. Maternal serum Arg, Cit, and Asp at day 138 were greater (P < 0.01) for CON compared with RES and RES-ARG; serum Orn at day 138 was greater (P = 0.04) for CON compared with RES. Maternal serum Cit at parturition was greater (P ≤ 0.03) for CON and RES-ARG compared with RES. Offspring serum Arg was affected by a maternal treatment by day of age interaction (P = 0.03), where at day 3, CON and RES-ARG had greater (P ≤ 0.03) serum Arg concentrations than RES, and at day 54, RES-ARG was greater than (P = 0.002) CON and RES was intermediate and did not differ from (P ≥ 0.09) CON and RES-ARG. Offspring serum Orn and Cit were less (P ≤ 0.03) for RES and RES-ARG compared with CON. Results indicate that distal tissue blood perfusion decreased due to maternal RES, and RES-ARG was able to improve perfusion but not to the level of CON ewes. Further, maternal RP-Arg altered offspring Arg and related amino acid concentrations during the postnatal period., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Maternal nutrients are essential for proper fetal and placental development and function. However, the effects of vitamin and mineral supplementation under two rates of maternal weight gain on placental genome-wide gene expression have not been investigated so far. Furthermore, biological processes and pathways in the placenta that act in response to early maternal nutrition are yet to be elucidated. Herein, we examined the impact of maternal vitamin and mineral supplementation (from pre-breeding to day 83 post-breeding) and two rates of gain during the first 83 days of pregnancy on the gene expression of placental caruncles (CAR; maternal placenta) and cotyledons (COT; fetal placenta) of crossbred Angus beef heifers. We identified 267 unique differentially expressed genes (DEG). Among the DEGs from CAR, we identified ACAT2, SREBF2 , and HMGCCS1 that underlie the cholesterol biosynthesis pathway. Furthermore, the transcription factors PAX2 and PAX8 were over-represented in biological processes related to kidney organogenesis. The DEGs from COT included SLC2A1 , SLC2A3 , SLC27A4 , and INSIG1. Our over-representation analysis retrieved biological processes related to nutrient transport and ion homeostasis, whereas the pathways included insulin secretion, PPAR signaling, and biosynthesis of amino acids. Vitamin and mineral supplementation and rate of gain were associated with changes in gene expression, biological processes, and KEGG pathways in beef cattle placental tissues.

The objective of this study was to evaluate the effects of feeding vitamin and mineral (VTM) supplement and (or) rate of gain (GAIN) during early gestation on amino acid (AA) concentrations in allantoic fluid (ALF) and amniotic fluid (AMF) and maternal serum. Seventy-two crossbred Angus heifers (initial BW = 359.5 ± 7.1 kg) were randomly assigned to one of four treatments in a 2 × 2 factorial arrangement with main effects of VTM supplement (VTM or NoVTM) and rate of gain (GAIN; low gain [LG], 0.28 kg/d, vs. moderate gain [MG], 0.79 kg/d). The VTM treatment (113 g•heifer-1•d-1, provided macro and trace minerals and vitamins A, D, and E to meet 110% of the requirements specified by the NASEM in Nutrient requirements of beef cattle. Washington, DC: The National Academies Press. doi:10.17226/19014, 2016) was initiated 71 to 148 d before artificial insemination (AI). To complete the factorial arrangement of treatments, at breeding heifers were either maintained on the basal diet (LG), or received MG diet which was implemented by adding a protein/energy supplement to the LG diet. Thirty-five gestating heifers with female fetuses were ovariohysterectomized on d 83 of gestation and maternal serum, ALF, and AMF were collected. Samples were analyzed for concentrations of neutral AA: Ala, Asn, Cys, Gln, Gly, Ile, Leu, Met, Phe, Pro, Ser, Thr, Trp, Tyr, and Val; cationic AA: Arg, His, and Lys; and anionic AA: Asp and Glu. In serum, a VTM × GAIN interaction (P = 0.02) was observed for Glu, with greater concentrations for VTM-LG than VTM-MG. Concentrations of serum Cys, Met, and Trp were greater (P ≤ 0.03) for MG than LG. In ALF, concentrations of Glu were affected by a VTM × GAIN interaction, where VTM-MG was greater (P < 0.01) than all other treatments. Further, ALF from VTM had increased (P ≤ 0.05) concentrations of His, Asp, and 12 of the 14 neutral AA; whereas GAIN affected concentrations of Arg, Cys, and Asp, with greater concentrations (P ≤ 0.05) in MG heifers. In AMF, AA concentrations were not affected (P ≥ 0.10) by VTM, GAIN, or their interaction. In conclusion, increased concentrations of AA in maternal serum and ALF of beef heifers were observed at d 83 of gestation in response to VTM supplementation and rate of gain of 0.79 kg/d, which raises important questions regarding the mechanisms responsible for AA uptake and balance between the maternal circulation and fetal fluid compartments., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We hypothesized that maternal nutrition during the first 50 d of gestation would influence the abundance of hexose transporters, SLC2A1, SLC2A3, and SLC2A5, and cationic amino acid transporters, SLC7A1 and SLC7A2, in heifer uteroplacental tissues. Angus-cross heifers (n = 43) were estrus synchronized, bred via artificial insemination, and assigned at breeding to 1 of 2 dietary intake groups (CON = 100% of requirements to achieve 0.45 kg/d of BW gain or RES = 60% of CON intake) and ovariohysterectomized on day 16, 34, or 50 of gestation (n = 6 to 9/d) in a completely randomized design with a 2 × 3 factorial arrangement of treatments. Uterine cross-sections were collected from the horn ipsilateral to the corpus luteum, fixed in 10% neutral buffered formalin, sectioned at 5 µm, and stained via immunofluorescence for transporters. For each image, areas of fetal membrane (FM; chorioallantois), luminal epithelium (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 for days 34 and 50. No transporters in target areas were influenced by a day × treatment interaction (P ≥ 0.06). In ENDO, all transporters were differentially abundant from days 16 to 50 of gestation (P ≤ 0.04), and SLC7A2 was greater (P = 0.05) for RES vs. CON. In SG, SLC7A1 and SLC7A2 were greater (P ≤ 0.04) at day 34 vs. day 16. In DG, SLC2A3 and SLC7A1 were greater (P ≤ 0.05) for CON vs. RES heifers; furthermore, SLC7A1 was greater (P < 0.01) at day 50 vs. days 16 and 34 of gestation. In MYO, SLC7A1 was greater (P < 0.01) for CON vs. RES and was greater (P = 0.02) at days 34 and 50 vs. day 16. There were no differences in FM (P ≥ 0.06). Analysis of all uterine tissues at day 16 determined that SLC2A1, SLC2A3, and SLC7A2 were all differentially abundant across uterine tissue type (P < 0.01), and SLC7A1 was greater (P = 0.02) for CON vs. RES. Analysis of all uteroplacental tissues at days 34 and 50 demonstrated that all transporters differed (P < 0.01) across uteroplacental tissues, and SLC7A1 was greater (P < 0.01) for CON vs. RES. These data are interpreted to imply that transporters are differentially affected by day of gestation, and that hexose and cationic amino acid transporters are differentially abundant across utero-placental tissue types, and that SLC7A1 is responsive to maternal nutritional treatment., (Published by Oxford University Press on behalf of the American Society of Animal Science 2020.)

Sixty nonpregnant, nulliparous Rambouillet ewes (51 ± 1.4 kg initial body weight) were used in a completely randomized design to determine 1) if rumen-protected l-Arg (RP-ARG) supplementation would increase serum concentrations of amino acids resulting from Arg supplementation and metabolism, and decrease serum concentrations of amino acids that compete with Arg for transporters, 2) if RP-ARG supplementation would alter carotid artery hemodynamics, and 3) the most effective oral dose of RP-ARG to positively increase both circulating amino acids and improve peripheral tissue blood perfusion as measured by carotid hemodynamics. Ewes were penned individually in a temperature-controlled facility. Ewes were randomly assigned to one of four treatments: a control group that received no supplemental Arg (CON; 50 g of finely ground corn, only), or Arg-supplemented groups that received 90 (90), 180 (180), or 360 (360) mg RP-ARG·kg BW-1·d-1 mixed in 50 g of finely ground corn. Supplements were administered once daily for 14 d and fully consumed before the delivery of a total pelleted diet at 0630 and 1830 hours daily. Baseline and final blood samples were collected at days 0 (before treatment initiation) and 15, respectively. Doppler ultrasound was used to assess carotid arterial hemodynamics at 0600 hours on days 0 (before treatment initiation), 5, 8, 12, and 15. After 14 d of supplementation, ewes fed 180 had greater Arg (P = 0.05) and Orn (P = 0.05) and tended (P = 0.08) to have greater Asp in serum than ewes fed 90, and for these amino acids, ewes fed 180 were similar (P ≥ 0.16) compared with ewes fed 360. All supplemented ewes (90, 180, and 360) had a negative change (P = 0.02) from baseline when normalized to CON for the pulsatility and resistance indices, which indicate greater distal tissue blood perfusion and lower vascular resistance of blood flow, respectively. Additionally, there were quadratic responses for the pulsatility and resistance indices (P = 0.03 and 0.01, respectively) where ewes fed 180 had the greatest change from baseline when normalized to CON. Results indicate that Arg supplementation increased serum amino acid concentrations and improved peripheral tissue blood perfusion. The 180 mg·kg BW-1·d-1 RP-ARG dose was determined to be the optimal dose for nonpregnant, nulliparous Rambouillet ewes., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study aimed to evaluate the effects of plane of nutrition and advancing days of pregnancy (DP) on maternal body composition and fetal development. Differing planes of nutrition were established by 2 feeding regimens (FR): ad libitum (AL) or maintenance (MA). Sixty-two nonlactating multiparous Holstein × Gyr cows with average body weight of 480 ± 10.1 kg and an age of 5 ± 0.5 yr were used. Cows were divided into 3 groups: pregnant (n = 44), nonpregnant (n = 12), and baseline reference cows (n = 6). The 56 pregnant and nonpregnant cows were randomly allocated into 2 different FR: AL or MA. Cows fed at MA received 1.15% of their body weight on a dry matter (DM) basis, receiving corn silage and a concentrate-based diet at a ratio of 93:7 on a DM basis. Reference group cows were slaughtered at the beginning of the experimental period to estimate body composition and empty body weight. To evaluate the effects of DP, pregnant and nonpregnant animals were slaughtered at d 140, 200, 240, and 270 of gestation. Feeding regimen affected maternal tissue composition. Days of pregnancy affected fresh weight (FW), DM, and energy content, but no differences were observed for crude protein (CP) and ether extract (EE) because of DP. Feeding regimen affected mammary gland components (CP, EE, and energy content), but not fresh or dry weights. Days of pregnancy influenced almost all mammary gland components except energy content. Regarding the uterus, FR affected only fresh and dry weights; however, DP affected every uterus component measured. The only interaction between FR and DP in this study was observed for placental FW. Cows fed AL on d 270 presented the same placental FW as cows at MA and AL on d 200 and 240. Further, pregnant cows fed at MA on d 270 had greater placental FW than cows fed AL at this day. Days of pregnancy, but not FR, influenced the composition of fetal fluids in pregnant cows. Finally, cows fed at MA had greater FW for the fetus than cows fed AL; however, fetus composition changed over DP. The FW, DM, EE, and energy content increased until d 270, but CP decreased. In conclusion, the novelty of our data presents how changes due to FR and DP occur in maternal tissues and the conceptus., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Effects of dietary crude protein (CP) supply on intake, digestibility, performance, and N balance were evaluated in young Nellore bulls consuming static or oscillating CP concentrations. Forty-two young bulls (initial BW of 260 ± 8.1 kg; age of 7 ± 1.0 mo) were fed ad libitum and were randomly assigned to receive one of six diets with different CP concentrations for 140 d: 105 (LO), 125 (MD), or 145 g CP /kg DM (HI), and LO to HI (LH), LO to MD (LM), or MD to HI (MH) oscillating CP at a 48-h interval for each feed. At the end of the experiment, bulls were slaughtered to evaluate carcass characteristics. Linear and quadratic effects were used to compare LO, MD, and HI, and specific contrasts were applied to compare oscillating dietary CP treatments vs. MD (125 g CP/kg DM) static treatment. Dry matter intake (DMI) was not affected ( P > 0.26) by increasing or oscillating dietary CP. As dietary N concentration increased, there was a subsequent increase in apparent N compounds digestibility ( P = 0.02), and no significant difference ( P = 0.38) was observed between oscillating LH and MD. Daily total urinary and fecal N increased ( P < 0.01) in response to increasing dietary CP. Significant differences were observed between oscillating LM and MH vs. MD, where bulls receiving the LM diet excreted less ( P < 0.01; 71.21 g/d) and bulls fed MH excreted more ( P < 0.01) urinary N (90.70 g/d) than those fed MD (85.52 g/d). A quadratic effect was observed ( P < 0.01) for retained N as a percentage of N intake, where the bulls fed LO had greater N retention than those fed HI, 16.20% and 13.78%, respectively. Both LH and LM had greater ( P < 0.01) daily retained N when compared with MD. Performance and carcass characteristics were not affected ( P > 0.05) by increasing or oscillating dietary CP. Therefore, these data indicate that although there is no alteration in the performance of growing Nellore bulls fed with oscillating CP diets vs. a static level of 125 g CP/kg DM, nor static low (105 g CP/kg DM) and high (145 g CP/kg DM) levels; there may be undesirable increases in environmental N excretion when the average dietary CP content is increased. The results suggest that dietary CP concentrations of 105, 125 g/kg DM, or within this range can be indicated for finishing young Nellore bulls, since it reaches the requirements, reduces the environmental footprint related to N excretion, and may save on costs of high-priced protein feeds., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Society of Animal Science.)

The hypothesis of this study was that arginine supplementation would overcome negative effects of restricted maternal feed intake during the last two-thirds of gestation on ewe performance and positively affect postnatal lamb growth and development. Multiparous, Rambouillet ewes (n = 32) were allocated to 3 treatments in a completely random design at 54 ± 3.9 d of gestation. Dietary treatments were 100% of nutrient requirements (control, CON), 60% of control (restricted, RES), or RES plus a rumen-protected arginine supplement dosed at 180 mg/kg BW once daily (RES-ARG). Ewes were penned individually in a temperature-controlled facility. At parturition, lambs were immediately removed from dams and reared independently. At day 54 ± 3 of age, lambs were stunned using captive bolt, exsanguinated, and organs were collected and weighed. Ewe BW from day 68 of gestation through parturition was greater (P ≤ 0.03) in CON compared with RES or RES-ARG. Similarly, ewe BCS from day 68 of gestation through parturition was greater (P ≤ 0.03) in CON than either RES or RES-ARG. Total ewe colostrum mass (g) at 3 h after parturition was greater (P ≤ 0.001) in CON than RES or RES-ARG. Lamb birth weight was greater (P = 0.04) in CON than RES ewes and tended (P = 0.10) to be greater in CON vs. RES-ARG. Lambs born to CON ewes had greater (P ≤ 0.03) BW than lambs from RES ewes at 7, 14, and 33 d postpartum. On day 19, lambs from CON and RES-ARG ewes both had greater (P ≤ 0.04) BW than lambs from RES ewes (12.0 and 11.5 vs. 10.3 ± 0.41 kg, respectively). Lambs born to CON and RES-ARG ewes had greater (P ≤ 0.04) ADG than lambs from RES ewes on day 19 (355.0 and 354.0 vs. 306.4 ± 15.77 g, respectively). Lambs from CON and RES-ARG ewes also had greater (P ≤ 0.02) girth circumference than lambs from RES ewes on day 19 (55.4 and 54.6 vs. 51.3 ± 0.97 cm, respectively). On day 54, lambs from RES-ARG ewes had greater (P = 0.003) curved crown rump length than lambs from RES ewes (99.8 vs. 93.9 ± 1.28 cm, respectively). Adrenal glands in lambs from CON dams had greater (P = 0.01) mass than adrenal glands in lambs from RES dams. Livers from lambs born to RES-ARG ewes weighed more (P = 0.05) than livers from lambs born to RES ewes. These results confirm our hypothesis that arginine supplementation during the last two-thirds of gestation can mitigate offspring, but not maternal negative consequences associated with restricted maternal nutrition.

To determine the effects of maternal supranutritional selenium (Se) supplementation and maternal nutritional plane on offspring growth potential, ewes were randomly assigned to 1 of 6 treatments in a 2 × 3 factorial arrangement [dietary Se (adequate Se; 9.5 μg/kg body weight vs. high Se; 81.8 μg/kg body weight initiated at breeding) and plane of nutrition [60%, 100%, or 140% of requirements; initiated on day 50 of gestation]]. Lambs were immediately removed from dams at birth and reared. Cortisol concentrations at birth were similar, but by 24 h, a relationship (P = 0.02) between maternal Se supplementation and nutritional plane on cortisol concentrations was observed in lambs. A sex of offspring × day of age interaction (P = 0.01) and a maternal Se supplementation × nutritional plane × day of age interaction (P = 0.04) was observed for thyroxine concentrations. Differences in growth may be influenced by thyroid hormone production early in neonatal life.

Background: Objectives were to examine the effects of selenium (Se) supply and maternal nutritional plane during gestation on mammary gland growth, cellular proliferation, and vascularity at parturition and d 20 of lactation. Rambouillet primiparous ewes (n = 84) were allocated to treatments in a 2 x 3 factorial. Factors were dietary Se (adequate Se [ASe, 11.5 μg/kg BW] or high Se [HSe, 77.0 μg/kg BW]) and nutritional plane (60% [RES], 100% [CON], or 140% [EXC]). At parturition, lambs were removed and 42 ewes (7/treatment) were necropsied. Remaining ewes were fed a common diet meeting requirements for lactation and mechanically milked twice daily until necropsy on d 20. At both necropsy periods, mammary glands were dissected and tissues harvested. Samples were analyzed for RNA, DNA, and protein content, cell proliferation, and vascularity. Where interactions were present (P ≤ 0.05), least squares means from the highest-order interaction are presented., Results: Final body weight of ewes was least (P ≤ 0.002) in RES, intermediate for CON, and greatest for EXC, regardless of stage of the ewe at necropsy (parturition or d 20 of lactation). In ewes necropsied at parturition, mammary glands were heavier (P = 0.02) in EXC compared to RES, with CON intermediate. Concentration of RNA (mg/g) was decreased (P = 0.01) in EXC compared to CON at parturition. There was a tendency (P = 0.07) for a Se by nutrition interaction in percentage of cells proliferating where ASe-EXC ewes had greater (P ≤ 0.02) number of proliferating cells then all other treatments. Mammary vascular area tended (P = 0.08) to be affected by a Se by nutrition interaction where ASe-CON had less (P = 0.007) vascular area than HSe-CON ewes. In ewes necropsied at d 20 of lactation, the number of alveoli per area was decreased (P ≤ 0.05) in RES compared to CON and EXC-fed ewes., Conclusions: Results of this study indicate that proper maternal nutritional plane during gestation is important for mammary gland development, even out to d 20 of lactation.

To investigate the effects of maternal selenium (Se) supplementation and nutritional intake during gestation on hormone changes, percentage body weight (BW) change, and organ mass in neonatal lambs, ewes were allocated to differing Se levels (adequate Se (ASe, 11.5 μg/kg BW) or high Se (HSe, 77.0 μg/kg BW)) initiated at breeding and nutritional intake (60% (RES), 100% (CON), or 140% (HIGH) of NRC requirements) initiated at day 40 of gestation. At parturition, all lambs were removed from dams, fed common diets, and BW and blood samples were collected until day 19. There was a Se × nutritional intake × day interaction for percentage BW change from birth. Lambs born to ASe-HIGH ewes tended to have decreased BW change compared with ASe-CON and ASe-RES groups on day 7. Lambs from HSe-HIGH ewes tended to have increased BW change compared with HSe-RES and HSe-CON groups from days 7 to 19. At birth, there was a Se × sex of offspring interaction, in which male lambs from HSe ewes had decreased cortisol concentrations compared with all other lambs. By 24 h, lambs from RES ewes had decreased cortisol compared with those from HIGH ewes, with lambs from CON ewes being intermediate. Lambs from RES- and CON-fed ewes had greater thyroxine than HIGH ewes at 24 h. Organ masses on day 19 were mainly impacted by maternal nutritional intake and sex of the offspring. Birth weight alone did not predict growth performance during neonatal life. Moreover, despite a similar postnatal diet, maternal nutritional plane and Se status did impact neonatal endocrine profiles. Exact mechanisms of how neonatal endocrine status can influence later growth and development need to be determined.

Using a mid- to late-gestation ovine model of intrauterine growth restriction (IUGR), we examined uteroplacental blood flow and fetal growth during melatonin supplementation as a 2 × 2 factorial design. At day 50 of gestation, 32 ewes were supplemented with 5 mg of melatonin (MEL) or no melatonin (CON) and were allocated to receive 100% [adequate; (ADQ)] or 60% [restricted (RES)] of nutrient requirements until day 130 of gestation. Umbilical artery blood flow was increased from day 60 to day 110 of gestation in MEL vs. CON dams, while umbilical artery blood flow was decreased from day 80 to day 110 of gestation in RES vs. ADQ dams. At day 130 of gestation, uteroplacental hemodynamics, measured under general anesthesia, and fetal growth were evaluated. Uterine artery blood flow was decreased in RES vs. ADQ dams, while melatonin supplementation did not affect uterine artery blood flow. Total placentome weight and placentome number were not different between treatment groups. Fetal weight was decreased by nutrient restriction. Abdominal girth and ponderal index were increased in fetuses from MEL-ADQ dams vs. all other groups. Fetal biparietal distance was decreased in CON-RES vs. CON-ADQ dams, while melatonin supplementation rescued fetal biparietal distance. Fetal kidney length and width were increased by maternal melatonin treatment. Fetal cardiomyocyte area was altered by both maternal melatonin treatment and nutritional plane. In summary, melatonin may negate the consequences of IUGR during specific abnormalities in umbilical blood flow as long as sufficient uterine blood perfusion is maintained during pregnancy.

Objectives were to determine the effects of maternal dietary supranutritional Se and nutritional plane during gestation on capillary surface density, capillary area density, and angiogenic factor expression in the developing mammary gland of primiparous ewes. Selenium treatments were initiated at breeding [adequate Se (ASe; 9.5 μg/kg of body weight) vs. high Se (HSe; 81.8 μg/kg of body weight)] and nutritional planes at d 50 of gestation [Low, 60%; moderate (Mod), 100%; and High, 140% of requirements). Mammary glands were collected within 24h postpartum. Vascular development was assessed in the glandular portion of the mammary gland. Vascularity was determined for mammary tissue with the following measurements taken: the cross-sectional capillary area density (total capillary area as a proportion of tissue area) and capillary surface density (CSD; total capillary circumference per unit of tissue area). High-Se ewes had greater capillary surface and area densities compared with ASe ewes. A tendency existed for an Se × plane of nutrition interaction for CSD with maternal diet not affecting CSD in HSe ewes, but Low ewes had a decreased CSD compared with Mod ewes, with High being intermediate in ASe ewes. Moreover, HSe-Low and HSe-High ewes had increased CSD compared with ASe-Low and ASe-High, respectively. Although Se status did not influence angiogenic factor mRNA expression, mammary glands from Low ewes tended to have increased VEGF and FLT1 mRNA expression compared with High ewes, with Mod being intermediate. Maternal plane of nutrition did not affect mammary gland glutathione peroxidase activity, but it was increased in HSe compared with ASe ewes. Increased mammary capillary nutrient exchange area may contribute to previously observed changes in colostrum quality., (Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)