The luteinizing hormone (LH) is well established to trigger oocyte maturation and cumulus expansion in preovulatory follicles, primarily through activating the epidermal growth factor (EGF) signaling network. While previous studies have demonstrated that activation of the G protein-coupled estrogen receptor (GPR30) accelerates meiotic resumption and first polar body extrusion in oocytes, the molecular mechanisms underlying GPR30 function in this process remain poorly defined. Here, cumulus-oocyte complexes (COCs) of goat follicles were used to investigate the interaction between the EGF network and GPR30 during oocyte maturation and ovulation. Our results showed that: LH signal was found to increase GPR30 protein levels via the EGF receptor signaling pathway (P＜0.05); Estradiol (E2) acts via GPR30 to promote ERK1/2 phosphorylation, cyclic adenosine monophosphate (cAMP) production, first polar body extrusion, and the expression of cumulus expansion-related genes in COCs (P＜0.05), and E2 further enhances these functional outcomes by increasing EGFR protein levels in cumulus cells. Collectively, these findings reveal a synergistic interaction between LH and E2 in regulating goat oocyte maturation: E2, via GPR30-mediated upregulation of EGFR, enhances COCs' responsiveness to LH-induced EGF signaling-thereby amplifying oocyte maturation efficiency and cumulus expansion. This study provides new insights into the integrated signaling network governing mammalian oocyte maturation and offers a potential molecular target for optimizing in vitro maturation (IVM) protocols for goat.
{"title":"Cooperation of luteinizing hormone and estradiol in the promotion of goat oocyte maturation via regulation and activation of the GPR30 and EGFR signaling pathways.","authors":"Baijuan Yue,Jie Liu,Sihai Lu,Meini Yu,Lele Zhu,Yaju Tang,Xiaoe Zhao,Sha Peng,Menghao Pan,Qiang Wei,Baohua Ma","doi":"10.1093/jas/skaf462","DOIUrl":"https://doi.org/10.1093/jas/skaf462","url":null,"abstract":"The luteinizing hormone (LH) is well established to trigger oocyte maturation and cumulus expansion in preovulatory follicles, primarily through activating the epidermal growth factor (EGF) signaling network. While previous studies have demonstrated that activation of the G protein-coupled estrogen receptor (GPR30) accelerates meiotic resumption and first polar body extrusion in oocytes, the molecular mechanisms underlying GPR30 function in this process remain poorly defined. Here, cumulus-oocyte complexes (COCs) of goat follicles were used to investigate the interaction between the EGF network and GPR30 during oocyte maturation and ovulation. Our results showed that: LH signal was found to increase GPR30 protein levels via the EGF receptor signaling pathway (P＜0.05); Estradiol (E2) acts via GPR30 to promote ERK1/2 phosphorylation, cyclic adenosine monophosphate (cAMP) production, first polar body extrusion, and the expression of cumulus expansion-related genes in COCs (P＜0.05), and E2 further enhances these functional outcomes by increasing EGFR protein levels in cumulus cells. Collectively, these findings reveal a synergistic interaction between LH and E2 in regulating goat oocyte maturation: E2, via GPR30-mediated upregulation of EGFR, enhances COCs' responsiveness to LH-induced EGF signaling-thereby amplifying oocyte maturation efficiency and cumulus expansion. This study provides new insights into the integrated signaling network governing mammalian oocyte maturation and offers a potential molecular target for optimizing in vitro maturation (IVM) protocols for goat.","PeriodicalId":14895,"journal":{"name":"Journal of animal science","volume":"177 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Germán D Ramírez-Zamudio, Wellison J S Diniz, Jennifer L Hurlbert, Priyanka Banerjee, Roberta B A Dahlen, Ana Clara B Menezes, Kendall C Swanson, Carl R Dahlen
Supplementation with vitamins and minerals (VTM) in the diet of pregnant F0 dams influences offspring development; however, long-term effects on metabolic organs, including the liver, remain unclear. This study evaluated hepatic gene expression in F1 heifers born to F0 dams fed a basal diet with VTM (n = 8) or without VTM (CON; n = 7) throughout gestation. After birth, F1 heifers were managed as a single group and inseminated with sexed female semen from a single sire. At 250 days of gestation and ∼22 months of age, F1 heifers were harvested and liver samples collected. Total RNA was extracted, sequenced, and reads aligned using STAR after quality control. Differential expression analyses were performed in R (v4.4.2) using the DESeq2 package, and over-representation of KEGG pathways and biological processes was carried out using ShinyGO v.0.76. A total of 13,990 genes were tested, of which 486 were differentially expressed (P ≤ 0.05; |log2FC| ≥ 0.5), including 241 upregulated and 245 downregulated in the VTM group. Upregulated genes by maternal VTM supplementation included RPL23, SOX4, PTGS2, NDUFC1, UQCRH, and RPS28, associated with pathways including ribosome and processes like cell proliferation and oxidative phosphorylation. Downregulated genes, including EIF2AK2, ESR1, SLC7A1, and PIK3CB, were associated with processes related to regulation of cell population proliferation and organonitrogen compound biosynthetic process. These results indicate that VTM supplementation in F0 dams may induce persistent changes in hepatic gene expression in the offspring, with potential metabolic implications during critical physiological stages, such as during gestation in F1 heifers. (Supported by USDA 2022-67016-36479)
{"title":"45 Vitamin and mineral supplementation in pregnant F0 beef dams may induce persistent changes in the hepatic transcriptome of F1 heifers","authors":"Germán D Ramírez-Zamudio, Wellison J S Diniz, Jennifer L Hurlbert, Priyanka Banerjee, Roberta B A Dahlen, Ana Clara B Menezes, Kendall C Swanson, Carl R Dahlen","doi":"10.1093/jas/skaf398.038","DOIUrl":"https://doi.org/10.1093/jas/skaf398.038","url":null,"abstract":"Supplementation with vitamins and minerals (VTM) in the diet of pregnant F0 dams influences offspring development; however, long-term effects on metabolic organs, including the liver, remain unclear. This study evaluated hepatic gene expression in F1 heifers born to F0 dams fed a basal diet with VTM (n = 8) or without VTM (CON; n = 7) throughout gestation. After birth, F1 heifers were managed as a single group and inseminated with sexed female semen from a single sire. At 250 days of gestation and ∼22 months of age, F1 heifers were harvested and liver samples collected. Total RNA was extracted, sequenced, and reads aligned using STAR after quality control. Differential expression analyses were performed in R (v4.4.2) using the DESeq2 package, and over-representation of KEGG pathways and biological processes was carried out using ShinyGO v.0.76. A total of 13,990 genes were tested, of which 486 were differentially expressed (P ≤ 0.05; |log2FC| ≥ 0.5), including 241 upregulated and 245 downregulated in the VTM group. Upregulated genes by maternal VTM supplementation included RPL23, SOX4, PTGS2, NDUFC1, UQCRH, and RPS28, associated with pathways including ribosome and processes like cell proliferation and oxidative phosphorylation. Downregulated genes, including EIF2AK2, ESR1, SLC7A1, and PIK3CB, were associated with processes related to regulation of cell population proliferation and organonitrogen compound biosynthetic process. These results indicate that VTM supplementation in F0 dams may induce persistent changes in hepatic gene expression in the offspring, with potential metabolic implications during critical physiological stages, such as during gestation in F1 heifers. (Supported by USDA 2022-67016-36479)","PeriodicalId":14895,"journal":{"name":"Journal of animal science","volume":"5 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145894367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bradley Lawrence, Roberto Barea, Marisol Castillo, Silvia Peris, Jesus Acosta, Xandra Benthem de Grave, Francesc Molist, Deana Hancock
: Introduction Offspring from sows fed Zn, Cu and Mn in the metal methionine hydroxy analogue chelate (MHAC) form vs. sulfate form have been shown to have greater loin eye area at harvest. Data is lacking compared with other mineral sources. Objective Assess the impact of maternal feeding of MHAC or glycinate (Gly) minerals on offspring serum mineral concentration, loin depth and fat depth. Methods From 6 weeks pre-breeding through first gestation, diets were supplemented with 80 mg/kg Zn, 10 mg/kg Cu and 20 mg/kg Mn. From first through third lactation, Zn, Cu and Mn were provided at 50 mg/kg Zn, 10 mg/kg Cu and 20 mg/kg Mn. During parity 3, serum from 1 piglet/litter at 4-d, weaning and 14-d post-weaning was obtained from 20 litters/treatment. At each parity, muscle and backfat depth was determined for approximately 1,000 pigs/treatment. Results There was no treatment (P > 0.15) nor treatment × time interaction (P > 0.22) for serum mineral concentration. Serum Fe, Zn, Cu and Mn were highest at weaning (P < 0.001). Cu and Zn concentrations were 34% and 60% lower respectively at 14-d post-weaning than at 4-d of age. Parity 2 and 3 MHAC offspring had 0.5 mm (P < 0.01) and 1.0 mm (P < 0.001) more muscle depth at 122 kg. Backfat was lower in parity 1 (-0.2 mm; P < 0.01) and parity 3 (-0.4 mm; P < 0.001) MHAC offspring. Conclusions Offspring serum mineral concentration was highest at 4-d of age. Maternal trace mineral source appears to provide an opportunity to impact offspring loin and fat depth at harvest.
{"title":"29 Maternal mineral source impact on piglet serum mineral and carcass composition at harvest","authors":"Bradley Lawrence, Roberto Barea, Marisol Castillo, Silvia Peris, Jesus Acosta, Xandra Benthem de Grave, Francesc Molist, Deana Hancock","doi":"10.1093/jas/skaf398.023","DOIUrl":"https://doi.org/10.1093/jas/skaf398.023","url":null,"abstract":": Introduction Offspring from sows fed Zn, Cu and Mn in the metal methionine hydroxy analogue chelate (MHAC) form vs. sulfate form have been shown to have greater loin eye area at harvest. Data is lacking compared with other mineral sources. Objective Assess the impact of maternal feeding of MHAC or glycinate (Gly) minerals on offspring serum mineral concentration, loin depth and fat depth. Methods From 6 weeks pre-breeding through first gestation, diets were supplemented with 80 mg/kg Zn, 10 mg/kg Cu and 20 mg/kg Mn. From first through third lactation, Zn, Cu and Mn were provided at 50 mg/kg Zn, 10 mg/kg Cu and 20 mg/kg Mn. During parity 3, serum from 1 piglet/litter at 4-d, weaning and 14-d post-weaning was obtained from 20 litters/treatment. At each parity, muscle and backfat depth was determined for approximately 1,000 pigs/treatment. Results There was no treatment (P &gt; 0.15) nor treatment × time interaction (P &gt; 0.22) for serum mineral concentration. Serum Fe, Zn, Cu and Mn were highest at weaning (P &lt; 0.001). Cu and Zn concentrations were 34% and 60% lower respectively at 14-d post-weaning than at 4-d of age. Parity 2 and 3 MHAC offspring had 0.5 mm (P &lt; 0.01) and 1.0 mm (P &lt; 0.001) more muscle depth at 122 kg. Backfat was lower in parity 1 (-0.2 mm; P &lt; 0.01) and parity 3 (-0.4 mm; P &lt; 0.001) MHAC offspring. Conclusions Offspring serum mineral concentration was highest at 4-d of age. Maternal trace mineral source appears to provide an opportunity to impact offspring loin and fat depth at harvest.","PeriodicalId":14895,"journal":{"name":"Journal of animal science","volume":"15 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145847360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lisa A Vrooman, Josue Baeza, Ana C Lima, Eric Rhon-Calderon, Donald F Conrad, Benjamin A Garcia, Marisa S Bartolomei
Pregnancies utilizing Assisted Reproductive Technologies (ART) are associated with several complications including an increased risk of preeclampsia, placental abruption, and morbidly adherent placentas. Our work along with others has shown that placentas from mice conceived by in vitro fertilization (IVF) display overgrowth, impaired blood vessel development, altered gene expression and DNA methylation. These changes are associated with impaired fetal growth. We sought to identify the placental protein differences with IVF to inform potential interventions for improving ART procedures. Placental protein differences among IVF and spontaneously-conceived mouse concepti were analyzed in a sex-specific manner (n = 4-5 placentas/sex/experimental group/timepoint) by data-independent acquisition mass spectrometry at five timepoints covering shortly after placental formation through term (E11.5, 12.5, 14.5, 16.5, and 18.5). Peptides below 1% FDR were included, and statistical analysis was performed using Two-way ANOVA and Tukey HSD post hoc tests, and adjustment for multiple hypothesis testing. We observed normal, dynamic abundance changes for placental proteins over development. IVF induces an overall reduction in the abundance of several placental proteins at the earliest timepoint, E11.5. Several of the identified affected proteins are known to be important for placenta development and epigenetic regulation. Intriguingly, we observed most placental protein changes were observed among the female concepti but not the male concepti. To our knowledge, this is the first proteomic analysis of mouse placentas at multiple timepoints along gestation. We are currently conducting spatial transcriptomics experiments to determine if protein changes are associated with specific placental compartments.
{"title":"60 Investigating placental protein changes associated with Assisted Reproductive Technologies in a mouse model","authors":"Lisa A Vrooman, Josue Baeza, Ana C Lima, Eric Rhon-Calderon, Donald F Conrad, Benjamin A Garcia, Marisa S Bartolomei","doi":"10.1093/jas/skaf398.051","DOIUrl":"https://doi.org/10.1093/jas/skaf398.051","url":null,"abstract":"Pregnancies utilizing Assisted Reproductive Technologies (ART) are associated with several complications including an increased risk of preeclampsia, placental abruption, and morbidly adherent placentas. Our work along with others has shown that placentas from mice conceived by in vitro fertilization (IVF) display overgrowth, impaired blood vessel development, altered gene expression and DNA methylation. These changes are associated with impaired fetal growth. We sought to identify the placental protein differences with IVF to inform potential interventions for improving ART procedures. Placental protein differences among IVF and spontaneously-conceived mouse concepti were analyzed in a sex-specific manner (n = 4-5 placentas/sex/experimental group/timepoint) by data-independent acquisition mass spectrometry at five timepoints covering shortly after placental formation through term (E11.5, 12.5, 14.5, 16.5, and 18.5). Peptides below 1% FDR were included, and statistical analysis was performed using Two-way ANOVA and Tukey HSD post hoc tests, and adjustment for multiple hypothesis testing. We observed normal, dynamic abundance changes for placental proteins over development. IVF induces an overall reduction in the abundance of several placental proteins at the earliest timepoint, E11.5. Several of the identified affected proteins are known to be important for placenta development and epigenetic regulation. Intriguingly, we observed most placental protein changes were observed among the female concepti but not the male concepti. To our knowledge, this is the first proteomic analysis of mouse placentas at multiple timepoints along gestation. We are currently conducting spatial transcriptomics experiments to determine if protein changes are associated with specific placental compartments.","PeriodicalId":14895,"journal":{"name":"Journal of animal science","volume":"31 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145847369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
: Introduction Fetal plasma lipid concentrations are low, and cardiomyocytes rely on carbohydrates as their primary fuel source. Circulating lipid levels may be prematurely elevated by maternal dyslipidemia or parenteral nutrition in preterm neonates. In late-term fetal sheep, maximal respiration was lower in cardiomyocytes exposed to Intralipid infusion compared to Controls. It is unclear whether fetal cardiomyocyte metabolism is altered by Intralipid exposure during mid-gestation. Objective Test the hypothesis that maximal oxygen consumption rate (OCR) is lower in cardiomyocytes from mid-gestation fetal sheep exposed to 8-day Intralipid treatment compared to fetuses receiving vehicle infusion in utero. Methods Mid-gestation fetal sheep received Intralipid 20® or vehicle infusion from 89 to 97 days of gestation. Left ventricular cardiomyocytes were isolated and cultured. Maximal OCR was measured in cardiomyocytes with or without additional exposure to palmitic acid in vitro. Results There was a significant interaction among fetal sex and in vivo Intralipid treatment for maximal OCR in cardiomyocytes cultured in standard media (P=0.018); OCR was 30% lower in males receiving Intralipid treatment compared to male Controls (P=0.037). Maximal OCR was similar between Control and Intralipid cardiomyocytes exposed to palmitic acid in vitro. Conclusion These findings indicate that mid-gestation Intralipid treatment reduces cardiomyocyte OCR in a sex-dependent manner. Similarities between Control and Intralipid cardiomyocytes treated with palmitic acid in vitro suggest that the metabolic response to lipid substrate is not compounded by prior lipid exposure. (Supported by NIH R01HL146997)
{"title":"3 Metabolic response to premature lipid exposure in fetal cardiomyocytes","authors":"Neeka Barooni*, Leena Kadam, Sonnet S Jonker","doi":"10.1093/jas/skaf398.003","DOIUrl":"https://doi.org/10.1093/jas/skaf398.003","url":null,"abstract":": Introduction Fetal plasma lipid concentrations are low, and cardiomyocytes rely on carbohydrates as their primary fuel source. Circulating lipid levels may be prematurely elevated by maternal dyslipidemia or parenteral nutrition in preterm neonates. In late-term fetal sheep, maximal respiration was lower in cardiomyocytes exposed to Intralipid infusion compared to Controls. It is unclear whether fetal cardiomyocyte metabolism is altered by Intralipid exposure during mid-gestation. Objective Test the hypothesis that maximal oxygen consumption rate (OCR) is lower in cardiomyocytes from mid-gestation fetal sheep exposed to 8-day Intralipid treatment compared to fetuses receiving vehicle infusion in utero. Methods Mid-gestation fetal sheep received Intralipid 20® or vehicle infusion from 89 to 97 days of gestation. Left ventricular cardiomyocytes were isolated and cultured. Maximal OCR was measured in cardiomyocytes with or without additional exposure to palmitic acid in vitro. Results There was a significant interaction among fetal sex and in vivo Intralipid treatment for maximal OCR in cardiomyocytes cultured in standard media (P=0.018); OCR was 30% lower in males receiving Intralipid treatment compared to male Controls (P=0.037). Maximal OCR was similar between Control and Intralipid cardiomyocytes exposed to palmitic acid in vitro. Conclusion These findings indicate that mid-gestation Intralipid treatment reduces cardiomyocyte OCR in a sex-dependent manner. Similarities between Control and Intralipid cardiomyocytes treated with palmitic acid in vitro suggest that the metabolic response to lipid substrate is not compounded by prior lipid exposure. (Supported by NIH R01HL146997)","PeriodicalId":14895,"journal":{"name":"Journal of animal science","volume":"9 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145847506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kendall T Mesch*, Eileen I Chang, Collin S Painter, Tristan B Dear, Jane Stremming, Laura D Brown
: Introduction In a sheep model of placental insufficiency and fetal growth restriction (FGR), rates of branched-chain amino acid (BCAA) uptake into fetal hindlimb muscle and BCAA incorporation into muscle protein synthesis (MPS) were lower compared to normal controls. However, intracellular BCAA concentrations were higher in FGR muscle. Objective Test the hypothesis that molecular pathways regulating BCAA catabolism and MPS are downregulated in FGR muscle. Methods Pregnant ewes were housed in elevated temperatures to induce placental insufficiency and FGR and compared to controls (CON; n = 15/group). At 0.9 gestation, protein was isolated from fetal biceps femoris muscle and analyzed by Western Blot for regulators of BCAA catabolism (BCAT2, BCKDH, BCKDK, KLF15, PPM1K) and MPS (AKT, mTOR, RPS6, 4E-BP1). Student’s t-test was used (P<0.05 was significant). Results In the BCAA catabolism pathway, protein expression of BCAT2 was 37% lower (P<0.01); phosphorylated and total BCKDH were 31% and 27% lower, respectively (P<0.05); and KLF15, an activator of BCKDH, was 15% lower (P<0.05) in FGR vs. CON. In the MPS pathway, total AKT was 20% lower (P<0.05) and the ratio of phosphorylated to total RPS6 was 41% lower (P<0.05) in FGR vs. CON. Conclusion Molecular regulators of BCAA catabolism and MPS were reduced in FGR muscle, indicating less BCAA flux into catabolic pathways and decreased incorporation of BCAA into protein. We speculate that elevated intramuscular BCAAs are the result of decreased utilization by muscle and are instead used to promote fetal survival during FGR pregnancies. (Supported by NIH R01HD079404)
{"title":"35 Trainee Award: Regulators of branched-chain amino acid catabolism and activators of muscle protein synthesis are reduced in skeletal muscle of fetal growth-restricted sheep","authors":"Kendall T Mesch*, Eileen I Chang, Collin S Painter, Tristan B Dear, Jane Stremming, Laura D Brown","doi":"10.1093/jas/skaf398.029","DOIUrl":"https://doi.org/10.1093/jas/skaf398.029","url":null,"abstract":": Introduction In a sheep model of placental insufficiency and fetal growth restriction (FGR), rates of branched-chain amino acid (BCAA) uptake into fetal hindlimb muscle and BCAA incorporation into muscle protein synthesis (MPS) were lower compared to normal controls. However, intracellular BCAA concentrations were higher in FGR muscle. Objective Test the hypothesis that molecular pathways regulating BCAA catabolism and MPS are downregulated in FGR muscle. Methods Pregnant ewes were housed in elevated temperatures to induce placental insufficiency and FGR and compared to controls (CON; n = 15/group). At 0.9 gestation, protein was isolated from fetal biceps femoris muscle and analyzed by Western Blot for regulators of BCAA catabolism (BCAT2, BCKDH, BCKDK, KLF15, PPM1K) and MPS (AKT, mTOR, RPS6, 4E-BP1). Student’s t-test was used (P&lt;0.05 was significant). Results In the BCAA catabolism pathway, protein expression of BCAT2 was 37% lower (P&lt;0.01); phosphorylated and total BCKDH were 31% and 27% lower, respectively (P&lt;0.05); and KLF15, an activator of BCKDH, was 15% lower (P&lt;0.05) in FGR vs. CON. In the MPS pathway, total AKT was 20% lower (P&lt;0.05) and the ratio of phosphorylated to total RPS6 was 41% lower (P&lt;0.05) in FGR vs. CON. Conclusion Molecular regulators of BCAA catabolism and MPS were reduced in FGR muscle, indicating less BCAA flux into catabolic pathways and decreased incorporation of BCAA into protein. We speculate that elevated intramuscular BCAAs are the result of decreased utilization by muscle and are instead used to promote fetal survival during FGR pregnancies. (Supported by NIH R01HD079404)","PeriodicalId":14895,"journal":{"name":"Journal of animal science","volume":"29 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145847307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
: Introduction The placenta mediates the effects of changing maternal environments during gestation on fetal development and on fetal and maternal lifelong health. These studies investigated the effects of exposures during pregnancy on human placental function, gene expression and epigenetics, and the subsequent associations with fetal development. Methods We use ex vivo systems including placental perfusion, villous and trophoblast culture, multi-scale imaging, epigenetic, proteomic and transcriptome analysis as well as placental samples from our Southampton cohorts. Results Findings include maternal vitamin D levels, smoking, and poor diet during pregnancy associate with placental gene expression of key nutrient transporters. These transporters relate to fetal and neonatal growth and body composition as well as maternal body composition. We show localized placental activation of vitamin D that induces rapid effects on the placental transcriptome, epigenome and proteome that effect placental function and thereby fetal development, independent of vitamin D transfer. Conclusions Local vitamin D metabolism may also impact upon the interplay at the maternal-fetal interface. The structure and molecular profile of the endometrium during the window of implantation is being investigated in relation to the maternal environment. Cell population profiles and interactions along with endometrial gland cilia function and extracellular vesicles production are targeted as potential biomarkers to predict pregnancy outcome. This work involves endometrial organoid culture, 3D imaging and single cell transcriptomic analysis. These data demonstrate a complex interplay between vitamin D and the placenta and endometrium and may inform future interventions using vitamin D to support fetal development and maternal adaptations to pregnancy. (Supported by The Gerald Kerkut Trust, Wellbeing of Women, Wessex Medical Research, The Rosetree’s Trust)
{"title":"10 Maternal exposures and molecular regulation of the human placenta and endometrium","authors":"Jane K Cleal*","doi":"10.1093/jas/skaf398.008","DOIUrl":"https://doi.org/10.1093/jas/skaf398.008","url":null,"abstract":": Introduction The placenta mediates the effects of changing maternal environments during gestation on fetal development and on fetal and maternal lifelong health. These studies investigated the effects of exposures during pregnancy on human placental function, gene expression and epigenetics, and the subsequent associations with fetal development. Methods We use ex vivo systems including placental perfusion, villous and trophoblast culture, multi-scale imaging, epigenetic, proteomic and transcriptome analysis as well as placental samples from our Southampton cohorts. Results Findings include maternal vitamin D levels, smoking, and poor diet during pregnancy associate with placental gene expression of key nutrient transporters. These transporters relate to fetal and neonatal growth and body composition as well as maternal body composition. We show localized placental activation of vitamin D that induces rapid effects on the placental transcriptome, epigenome and proteome that effect placental function and thereby fetal development, independent of vitamin D transfer. Conclusions Local vitamin D metabolism may also impact upon the interplay at the maternal-fetal interface. The structure and molecular profile of the endometrium during the window of implantation is being investigated in relation to the maternal environment. Cell population profiles and interactions along with endometrial gland cilia function and extracellular vesicles production are targeted as potential biomarkers to predict pregnancy outcome. This work involves endometrial organoid culture, 3D imaging and single cell transcriptomic analysis. These data demonstrate a complex interplay between vitamin D and the placenta and endometrium and may inform future interventions using vitamin D to support fetal development and maternal adaptations to pregnancy. (Supported by The Gerald Kerkut Trust, Wellbeing of Women, Wessex Medical Research, The Rosetree’s Trust)","PeriodicalId":14895,"journal":{"name":"Journal of animal science","volume":"14 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145847312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Juliet Henning, Lucas Branco, Genevieve VanWye, Morgan Brown, Chad Duit, Jordan M Thomas, Thiago Martins, Cecilia Constantino Rocha
Anogenital distance (AGD), distance from the anus to the clitoris is programmed during fetal life by testosterone concentrations. In rodents, fetal testosterone increases AGD and reduces reproductive performance in the adult life. We hypothesized that yearling beef heifers with a shorter AGD during the gynecological examination have a greater probability of pregnancy by artificial insemination (AI) than heifers with longer AGD. Yearling heifers (n = 554) were submitted to estrous synchronization, gynecological examination (pre pubertal vs. pubertal) and AGD measures to the top of the clitoris (AGD-C) or to the dorsal commissure of the vulva (AGD-T). At CIDR withdrawal, heifers received an estrus patch. AI was conducted using 5 bulls. 30 days after AI pregnancy diagnosis was performed. 85% of the heifers were pubertal and 62% displayed estrus. AGD-C and AGD-T were positively associated (P < 0.001, R²= 0.1982). For each unit of increase in body weight AGD-C increased 0.0064 cm (P = 0.0003). AGD-C was positively associated with the probability of puberty (P = 0.0019) and pregnancy in heifers without a corpus luteum upon gynecological examination (P = 0.10). ROC curve analysis found a poor area under the curve (0.59) for any AGD to predict pregnancy/AI. In conclusion, it looks like in adult life the AGD effects on fertility are mostly a consequence of the increase in body weight the prenatal effects on the AGD are diluted over time and are not associated with reproductive outcome in adults.
{"title":"20 Using anogenital distance, a prenatal marker of androgen exposure, to predict pregnancy by artificial insemination in yearling beef heifers","authors":"Juliet Henning, Lucas Branco, Genevieve VanWye, Morgan Brown, Chad Duit, Jordan M Thomas, Thiago Martins, Cecilia Constantino Rocha","doi":"10.1093/jas/skaf398.016","DOIUrl":"https://doi.org/10.1093/jas/skaf398.016","url":null,"abstract":"Anogenital distance (AGD), distance from the anus to the clitoris is programmed during fetal life by testosterone concentrations. In rodents, fetal testosterone increases AGD and reduces reproductive performance in the adult life. We hypothesized that yearling beef heifers with a shorter AGD during the gynecological examination have a greater probability of pregnancy by artificial insemination (AI) than heifers with longer AGD. Yearling heifers (n = 554) were submitted to estrous synchronization, gynecological examination (pre pubertal vs. pubertal) and AGD measures to the top of the clitoris (AGD-C) or to the dorsal commissure of the vulva (AGD-T). At CIDR withdrawal, heifers received an estrus patch. AI was conducted using 5 bulls. 30 days after AI pregnancy diagnosis was performed. 85% of the heifers were pubertal and 62% displayed estrus. AGD-C and AGD-T were positively associated (P &lt; 0.001, R²= 0.1982). For each unit of increase in body weight AGD-C increased 0.0064 cm (P = 0.0003). AGD-C was positively associated with the probability of puberty (P = 0.0019) and pregnancy in heifers without a corpus luteum upon gynecological examination (P = 0.10). ROC curve analysis found a poor area under the curve (0.59) for any AGD to predict pregnancy/AI. In conclusion, it looks like in adult life the AGD effects on fertility are mostly a consequence of the increase in body weight the prenatal effects on the AGD are diluted over time and are not associated with reproductive outcome in adults.","PeriodicalId":14895,"journal":{"name":"Journal of animal science","volume":"121 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145847366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The uterine-placental interface is a dynamic site where uterine and trophoblast cells cooperate to establish a protective environment conducive to the redirection of resources facilitating development of the embryo. The rat and human possess a uterine-placental interface characterized by deep trophoblast cell infiltration into the uterine parenchyma. Invasive trophoblast cells direct changes in uterine immune, endothelial, smooth muscle, glandular epithelial, and stromal cell constituents, and effectively anchor the placenta to the uterus and restructure uterine spiral arteries. In the human, these invasive trophoblast cells are referred to as extravillous trophoblast cells. Trophoblast cell invasion and trophoblast-directed uterine spiral artery remodeling are critical events in the establishment of pregnancy. Failures in trophoblast-guided uterine transformation lead to obstetrical complications, including early pregnancy loss, preeclampsia, intrauterine growth restriction, and pre-term birth. Therefore, studying molecular mechanisms regulating development and function of the invasive trophoblast/extravillous trophoblast cell lineage is clinically relevant and is of considerable importance. Our research approach involves identification of candidate conserved regulatory pathways controlling invasive trophoblast/extravillous trophoblast cell lineage development using comparative transcriptomic approaches, evaluating the importance of the regulators using trophoblast stem cell models, and testing critical hubs within the pathways using relevant in vivo rat models. (Supported by NIH HD020676, HD105734, HD112559, and the Sosland Foundation)
{"title":"53 Trophoblast cells at the uterine-placental interface","authors":"Michael J Soares*","doi":"10.1093/jas/skaf398.045","DOIUrl":"https://doi.org/10.1093/jas/skaf398.045","url":null,"abstract":"The uterine-placental interface is a dynamic site where uterine and trophoblast cells cooperate to establish a protective environment conducive to the redirection of resources facilitating development of the embryo. The rat and human possess a uterine-placental interface characterized by deep trophoblast cell infiltration into the uterine parenchyma. Invasive trophoblast cells direct changes in uterine immune, endothelial, smooth muscle, glandular epithelial, and stromal cell constituents, and effectively anchor the placenta to the uterus and restructure uterine spiral arteries. In the human, these invasive trophoblast cells are referred to as extravillous trophoblast cells. Trophoblast cell invasion and trophoblast-directed uterine spiral artery remodeling are critical events in the establishment of pregnancy. Failures in trophoblast-guided uterine transformation lead to obstetrical complications, including early pregnancy loss, preeclampsia, intrauterine growth restriction, and pre-term birth. Therefore, studying molecular mechanisms regulating development and function of the invasive trophoblast/extravillous trophoblast cell lineage is clinically relevant and is of considerable importance. Our research approach involves identification of candidate conserved regulatory pathways controlling invasive trophoblast/extravillous trophoblast cell lineage development using comparative transcriptomic approaches, evaluating the importance of the regulators using trophoblast stem cell models, and testing critical hubs within the pathways using relevant in vivo rat models. (Supported by NIH HD020676, HD105734, HD112559, and the Sosland Foundation)","PeriodicalId":14895,"journal":{"name":"Journal of animal science","volume":"3 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145847416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Both genetic and environmental factors contribute to the development of Type 2 diabetes (T2D). Hyperinsulinemia is frequently observed in pregnant women with prediabetes, obesity, or gestational diabetes, and their offspring are at increased risk of developing T2D. However, there is a lack of longitudinal studies examining the long-term metabolic outcomes in offspring of hyperinsulinemic mothers. Moreover, the mechanistic link between maternal hyperinsulinemia and the programming of metabolic disease in offspring remains poorly understood. The prevailing view is that insulin does not cross the placenta to regulate fetal growth directly. Nonetheless, maternal insulin can function as a growth factor and anabolic hormone by binding to insulin receptors (IR) and insulin-like growth factor 1 receptors (IGF1R) on the placenta. This interaction can drive key placental functions, including nutrient transport to the fetus. As a result, maternal insulin may indirectly alter fetal development by modifying placental nutrient delivery to fetal metabolic tissues, potentially causing permanent changes that predispose offspring to T2D in adulthood. This seminar will examine the metabolic phenotypes of offspring born to hyperinsulinemic murine dams. It will also highlight findings on metabolic outcomes in offspring from otherwise normal pregnancies where insulin or IGF1 receptors were selectively deleted in the placenta during gestation. Finally, evidence from genetic mouse models demonstrating that both loss- and gain-of-function alterations in placental mTOR signaling can significantly influence susceptibility to type 2 diabetes will be presented. These effects appear to be mediated through changes in placental nutrient transport and subsequent altered nutrient sensing by fetal pancreatic beta cells in the offspring. Collectively, these observations support the concept that insulin/mTOR signaling in the placenta integrates maternal metabolic signals with fetal nutrient exposure, ultimately programming the metabolic health of the offspring.
{"title":"1 Unlocking metabolic fate: How placental insulin/IGF-1 and mTOR signaling shape offspring health","authors":"Emilyn U Alejandro*","doi":"10.1093/jas/skaf398.001","DOIUrl":"https://doi.org/10.1093/jas/skaf398.001","url":null,"abstract":"Both genetic and environmental factors contribute to the development of Type 2 diabetes (T2D). Hyperinsulinemia is frequently observed in pregnant women with prediabetes, obesity, or gestational diabetes, and their offspring are at increased risk of developing T2D. However, there is a lack of longitudinal studies examining the long-term metabolic outcomes in offspring of hyperinsulinemic mothers. Moreover, the mechanistic link between maternal hyperinsulinemia and the programming of metabolic disease in offspring remains poorly understood. The prevailing view is that insulin does not cross the placenta to regulate fetal growth directly. Nonetheless, maternal insulin can function as a growth factor and anabolic hormone by binding to insulin receptors (IR) and insulin-like growth factor 1 receptors (IGF1R) on the placenta. This interaction can drive key placental functions, including nutrient transport to the fetus. As a result, maternal insulin may indirectly alter fetal development by modifying placental nutrient delivery to fetal metabolic tissues, potentially causing permanent changes that predispose offspring to T2D in adulthood. This seminar will examine the metabolic phenotypes of offspring born to hyperinsulinemic murine dams. It will also highlight findings on metabolic outcomes in offspring from otherwise normal pregnancies where insulin or IGF1 receptors were selectively deleted in the placenta during gestation. Finally, evidence from genetic mouse models demonstrating that both loss- and gain-of-function alterations in placental mTOR signaling can significantly influence susceptibility to type 2 diabetes will be presented. These effects appear to be mediated through changes in placental nutrient transport and subsequent altered nutrient sensing by fetal pancreatic beta cells in the offspring. Collectively, these observations support the concept that insulin/mTOR signaling in the placenta integrates maternal metabolic signals with fetal nutrient exposure, ultimately programming the metabolic health of the offspring.","PeriodicalId":14895,"journal":{"name":"Journal of animal science","volume":"14 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145847418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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