: 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}
Wonders O Ogundare*, Linda M Beckett, Vishal Suresh, Theresa M Casey
: Introduction Greater colostrum intake increases milk production during lactation in mature sows and cows. Although, we know that the number of mammary epithelial cells drives milk production during lactation, the mechanism however, is not clearly understood. Thus, we aimed to evaluate how neonate colostrum and formula intake administered at varying levels, affect epithelial and stromal cell proliferation in the neonatal mammary gland. Methods We randomly assigned piglets to one of six treatment groups: bottle-fed pooled colostrum at 20% (COL 20, n = 10) or 10% (COL 10, n = 10) of body weight, milk replacer at 20% (MR 20, n = 10) or 10% (MR 10, n = 10) of body weight, suckled ad libitum on the sow (SOS, n = 9), or not fed (zero hour, ZH, n = 8). All groups were euthanized 24 hours postnatally except ZH which were euthanized immediately after birth. Mammary tissues were obtained, fixed, and stained with Ki67 to identify proliferating cells using ImageJ and analyzed statistically with SAS software. Results Colostrum significantly increased epithelial cell proliferation (P = 0.05) compared to formula. Higher feeding dose also significantly increased epithelial cells (P = 0.0003) and stroma cells (P = 0.0005) than lower dose. Notably, stroma proliferation was significantly higher (P < 0.05) in COL 20 compared to other groups including COL 10, MR 20, MR 10, SOS and ZH. Conclusion These findings indicate that sufficient colostrum intake promotes proliferation of epithelial and stromal cells in the neonatal mammary gland, suggesting a potential role in enhancing the gland’s future lactation capacity. (Funded by USDA 2110002200)
当前位置介绍大初乳摄入量可提高成熟母猪和奶牛的泌乳产奶量。虽然我们知道哺乳期间乳腺上皮细胞的数量驱动泌乳，但其机制尚不清楚。因此，我们旨在评估不同水平的新生儿初乳和配方奶摄入对新生儿乳腺上皮细胞和基质细胞增殖的影响。方法将仔猪随机分为6个处理组，分别为体重的20% （COL 20, n = 10）或10% （COL 10, n = 10）混合初乳瓶饲组、体重的20% （MR 20, n = 10）或10% （MR 10, n = 10）代奶组、母猪自由喂奶组（SOS, n = 9）和不喂奶组（零时，ZH, n = 8）。除ZH组在出生后立即实施安乐死外，其余各组均在出生后24 h实施安乐死。取乳腺组织固定，用Ki67染色，用ImageJ识别增殖细胞，用SAS软件进行统计学分析。结果与配方奶相比，初乳显著提高了上皮细胞的增殖能力（P = 0.05）。饲喂剂量高也显著增加了上皮细胞（P = 0.0003）和基质细胞（P = 0.0005）。与COL 10、MR 20、MR 10、SOS和ZH组相比，COL 20组间质增殖显著增加（P < 0.05）。结论充足的初乳摄入可促进新生儿乳腺上皮细胞和基质细胞的增殖，可能对提高乳腺泌乳能力有潜在作用。（美国农业部资助2110002200）
{"title":"39 Colostrum intake promotes mammary cell proliferation in neonatal piglets","authors":"Wonders O Ogundare*, Linda M Beckett, Vishal Suresh, Theresa M Casey","doi":"10.1093/jas/skaf398.032","DOIUrl":"https://doi.org/10.1093/jas/skaf398.032","url":null,"abstract":": Introduction Greater colostrum intake increases milk production during lactation in mature sows and cows. Although, we know that the number of mammary epithelial cells drives milk production during lactation, the mechanism however, is not clearly understood. Thus, we aimed to evaluate how neonate colostrum and formula intake administered at varying levels, affect epithelial and stromal cell proliferation in the neonatal mammary gland. Methods We randomly assigned piglets to one of six treatment groups: bottle-fed pooled colostrum at 20% (COL 20, n = 10) or 10% (COL 10, n = 10) of body weight, milk replacer at 20% (MR 20, n = 10) or 10% (MR 10, n = 10) of body weight, suckled ad libitum on the sow (SOS, n = 9), or not fed (zero hour, ZH, n = 8). All groups were euthanized 24 hours postnatally except ZH which were euthanized immediately after birth. Mammary tissues were obtained, fixed, and stained with Ki67 to identify proliferating cells using ImageJ and analyzed statistically with SAS software. Results Colostrum significantly increased epithelial cell proliferation (P = 0.05) compared to formula. Higher feeding dose also significantly increased epithelial cells (P = 0.0003) and stroma cells (P = 0.0005) than lower dose. Notably, stroma proliferation was significantly higher (P &lt; 0.05) in COL 20 compared to other groups including COL 10, MR 20, MR 10, SOS and ZH. Conclusion These findings indicate that sufficient colostrum intake promotes proliferation of epithelial and stromal cells in the neonatal mammary gland, suggesting a potential role in enhancing the gland’s future lactation capacity. (Funded by USDA 2110002200)","PeriodicalId":14895,"journal":{"name":"Journal of animal science","volume":"26 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145847510","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}
Upasna Sharma, Simeiyun Liu, Andrew D Holmes, Sol Katzman
: Introduction Transmission of parental traits to offspring is the most fundamental process for the perpetuation of life and is vital for the process of evolution. Although there is mounting evidence from worms to humans that parental environment can influence phenotypes in offspring, the mechanism of such intergenerational inheritance remains deeply mysterious. Our previous studies implicated sperm small RNAs in intergenerational epigenetic inheritance of paternal environmental effects. We found that cleavage products of tRNAs, known as tRNA-derived small RNAs or tRNA fragments (tRF), are highly abundant in mature sperm and environmental conditions alter their levels. A 5’ fragment of tRNA-Valine-CAC-2 (tRFValCAC) as one of the most abundant tRNA fragments in mature mouse sperm. tRFValCAC is enriched in sperm during epididymal maturation, and extracellular vesicles (EVs) secreted by epididymal epithelial cells can deliver tRFValCAC to sperm. Objective Here, we investigated how tRFValCAC is delivered to sperm and what functions it carries out upon deposition in the embryo at fertilization to elucidate the mechanism of sperm tRF-mediated intergenerational inheritance. Methods We used a combination of RNA-sequencing, assisted reproduction, and embryo microinjections to study the dynamics and functions of tRFValCAC. Results Our studies demonstrate that heterogeneous nuclear ribonucleoprotein A/B (hnRNPAB) binds tRFValCAC in the epididymis and regulates its abundance in EVs, thereby modulating its levels in sperm. Inhibition of tRFValCAC in preimplantation embryos alters transcript abundance of genes involved in RNA splicing and mRNA processing, dysregulates alternative splicing, and delays preimplantation development. Conclusions Our work revealed that a sperm-enriched tRF regulates early embryonic gene expression and the pace of preimplantation development, providing a potential mechanism of sperm small RNAs-mediated intergenerational inheritance. (Supported by NIH 1DP2AG066622-01, Searle Scholars Program 20-SSP-109)
{"title":"51 Intergenerational transmission of paternal environmental effects via sperm small RNAs in mice","authors":"Upasna Sharma, Simeiyun Liu, Andrew D Holmes, Sol Katzman","doi":"10.1093/jas/skaf398.044","DOIUrl":"https://doi.org/10.1093/jas/skaf398.044","url":null,"abstract":": Introduction Transmission of parental traits to offspring is the most fundamental process for the perpetuation of life and is vital for the process of evolution. Although there is mounting evidence from worms to humans that parental environment can influence phenotypes in offspring, the mechanism of such intergenerational inheritance remains deeply mysterious. Our previous studies implicated sperm small RNAs in intergenerational epigenetic inheritance of paternal environmental effects. We found that cleavage products of tRNAs, known as tRNA-derived small RNAs or tRNA fragments (tRF), are highly abundant in mature sperm and environmental conditions alter their levels. A 5’ fragment of tRNA-Valine-CAC-2 (tRFValCAC) as one of the most abundant tRNA fragments in mature mouse sperm. tRFValCAC is enriched in sperm during epididymal maturation, and extracellular vesicles (EVs) secreted by epididymal epithelial cells can deliver tRFValCAC to sperm. Objective Here, we investigated how tRFValCAC is delivered to sperm and what functions it carries out upon deposition in the embryo at fertilization to elucidate the mechanism of sperm tRF-mediated intergenerational inheritance. Methods We used a combination of RNA-sequencing, assisted reproduction, and embryo microinjections to study the dynamics and functions of tRFValCAC. Results Our studies demonstrate that heterogeneous nuclear ribonucleoprotein A/B (hnRNPAB) binds tRFValCAC in the epididymis and regulates its abundance in EVs, thereby modulating its levels in sperm. Inhibition of tRFValCAC in preimplantation embryos alters transcript abundance of genes involved in RNA splicing and mRNA processing, dysregulates alternative splicing, and delays preimplantation development. Conclusions Our work revealed that a sperm-enriched tRF regulates early embryonic gene expression and the pace of preimplantation development, providing a potential mechanism of sperm small RNAs-mediated intergenerational inheritance. (Supported by NIH 1DP2AG066622-01, Searle Scholars Program 20-SSP-109)","PeriodicalId":14895,"journal":{"name":"Journal of animal science","volume":"5 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145847309","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}
Rebecca L Wilson, Baylea N Davenport, Alyssa Williams, Helen N Jones
: Introduction Chronic maternal stress during pregnancy can have lasting impacts on both maternal health and fetal development, yet the underlying maternal physiological adaptations remain poorly understood. Objective Investigate increased chronic maternal stress, through food insecurity, on maternal physiological parameters at two gestational (GD) timepoints. Methods Female Hartley guinea pigs were fed either an ad libitum (Control) or a restricted diet (MNR) from 4 weeks prior to pregnancy until sacrifice. MNR dams were provided food at 1000h daily which was generally consumed within 4-6h leaving a period of ∼18-20h without food. Dams were euthanized at GD35-38 (mid-pregnancy: Control n = 7, MNR n = 6) or GD57-63 (near-term: Control n = 6, MNR n = 6) and weights recorded. Maternal plasma was analyzed for various metabolic markers. Statistical significance was determined using generalized linear modelling. Results While maternal weight (minus fetal and maternal-fetal interface weight) and maternal-fetal interface weight increased between timepoints (P < 0.001, both respectively), they remained similar between MNR and Control. MNR maintained litter size but had reduced fetal weight at both mid-pregnancy and near-term (13-19%; P = 0.014). Between mid-pregnancy and near-term, maternal cortisol (P = 0.041), glucose (P = 0.001), and calcium (P = 0.004) increased, while progesterone (P < 0.001), lactate (P < 0.001), and sodium (P = 0.021) decreased. MNR dams showed elevated cortisol (53-85%, P = 0.016), progesterone (13-35%, P = 0.036), and BUN (8-38%, P = 0.012) and reduced cholesterol (24-32%, P = 0.019) compared to Controls at both gestational timepoints. Conclusion Chronic maternal stress from before pregnancy leads to a metabolic state characterized by elevated cortisol and altered energy utilization (increased BUN, decreased cholesterol), suggesting metabolic adaptations to prioritize maternal survival but with compromised fetal growth. (Supported by NIH K99HD109458 & R01HD090657)
{"title":"62 Investigating maternal physiological responses to pregnancy in a guinea pig model of increased maternal stress","authors":"Rebecca L Wilson, Baylea N Davenport, Alyssa Williams, Helen N Jones","doi":"10.1093/jas/skaf398.053","DOIUrl":"https://doi.org/10.1093/jas/skaf398.053","url":null,"abstract":": Introduction Chronic maternal stress during pregnancy can have lasting impacts on both maternal health and fetal development, yet the underlying maternal physiological adaptations remain poorly understood. Objective Investigate increased chronic maternal stress, through food insecurity, on maternal physiological parameters at two gestational (GD) timepoints. Methods Female Hartley guinea pigs were fed either an ad libitum (Control) or a restricted diet (MNR) from 4 weeks prior to pregnancy until sacrifice. MNR dams were provided food at 1000h daily which was generally consumed within 4-6h leaving a period of ∼18-20h without food. Dams were euthanized at GD35-38 (mid-pregnancy: Control n = 7, MNR n = 6) or GD57-63 (near-term: Control n = 6, MNR n = 6) and weights recorded. Maternal plasma was analyzed for various metabolic markers. Statistical significance was determined using generalized linear modelling. Results While maternal weight (minus fetal and maternal-fetal interface weight) and maternal-fetal interface weight increased between timepoints (P &lt; 0.001, both respectively), they remained similar between MNR and Control. MNR maintained litter size but had reduced fetal weight at both mid-pregnancy and near-term (13-19%; P = 0.014). Between mid-pregnancy and near-term, maternal cortisol (P = 0.041), glucose (P = 0.001), and calcium (P = 0.004) increased, while progesterone (P &lt; 0.001), lactate (P &lt; 0.001), and sodium (P = 0.021) decreased. MNR dams showed elevated cortisol (53-85%, P = 0.016), progesterone (13-35%, P = 0.036), and BUN (8-38%, P = 0.012) and reduced cholesterol (24-32%, P = 0.019) compared to Controls at both gestational timepoints. Conclusion Chronic maternal stress from before pregnancy leads to a metabolic state characterized by elevated cortisol and altered energy utilization (increased BUN, decreased cholesterol), suggesting metabolic adaptations to prioritize maternal survival but with compromised fetal growth. (Supported by NIH K99HD109458 & R01HD090657)","PeriodicalId":14895,"journal":{"name":"Journal of animal science","volume":"38 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145847310","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}
Lyle G Best, C Azure, H Davis, L Jeanotte, S LaRocque, S Poitra, J Poitra, S Standish, T J Parisien, K Morin
: Introduction Maternal variants including C-Reactive Protein, CRP rs1205 have previously been associated with risk of pre-eclampsia (PE). These findings were replicated in two non-American Indian populations. The rs1205 T allele is associated with reduced serum levels of CRP. Our objective was to determine if the fetal rs1205 genotype contributed to maternal risk of PE independent of maternal rs1205 genotype. Methods Only offspring of both case and control mothers heterozygous for rs1205 were enrolled, thus controlling for maternal genetic influence at this locus. Offspring were then genotyped for rs1205 by TaqMan assay. Association was assessed by chi-square and multivariate logistic regression. Results Offspring of 10 of 45 normal pregnancies and 11 of 24 PE pregnancies exhibited the rs1205 C allele recessive genotype (Pearson chi square p = 0.042). Multivariate logistic regression analysis adjusted for maternal age, nulliparity and BMI demonstrates an odds ratio of 3.603, p = 0.043, 95% CI 1.042-12.457 for the fetal, C recessive genotype. Discussion Among 69 women, heterozygous for the rs1205 allele, both chi-square and multivariate adjusted logistic analysis shows significant association of PE among pregnancies with fetal rs1205 C recessive genotypes. This is consistent with previous findings of reduced risk associated with this maternal genotype, and with a pathophysiologic model wherein increased placental CRP expression increases risk of PE. (Supported by NIGMS P20GM103442)
{"title":"4 Fetal c-reactive protein rs1205 genotype is associated with maternal pre-eclampsia","authors":"Lyle G Best, C Azure, H Davis, L Jeanotte, S LaRocque, S Poitra, J Poitra, S Standish, T J Parisien, K Morin","doi":"10.1093/jas/skaf398.004","DOIUrl":"https://doi.org/10.1093/jas/skaf398.004","url":null,"abstract":": Introduction Maternal variants including C-Reactive Protein, CRP rs1205 have previously been associated with risk of pre-eclampsia (PE). These findings were replicated in two non-American Indian populations. The rs1205 T allele is associated with reduced serum levels of CRP. Our objective was to determine if the fetal rs1205 genotype contributed to maternal risk of PE independent of maternal rs1205 genotype. Methods Only offspring of both case and control mothers heterozygous for rs1205 were enrolled, thus controlling for maternal genetic influence at this locus. Offspring were then genotyped for rs1205 by TaqMan assay. Association was assessed by chi-square and multivariate logistic regression. Results Offspring of 10 of 45 normal pregnancies and 11 of 24 PE pregnancies exhibited the rs1205 C allele recessive genotype (Pearson chi square p = 0.042). Multivariate logistic regression analysis adjusted for maternal age, nulliparity and BMI demonstrates an odds ratio of 3.603, p = 0.043, 95% CI 1.042-12.457 for the fetal, C recessive genotype. Discussion Among 69 women, heterozygous for the rs1205 allele, both chi-square and multivariate adjusted logistic analysis shows significant association of PE among pregnancies with fetal rs1205 C recessive genotypes. This is consistent with previous findings of reduced risk associated with this maternal genotype, and with a pathophysiologic model wherein increased placental CRP expression increases risk of PE. (Supported by NIGMS P20GM103442)","PeriodicalId":14895,"journal":{"name":"Journal of animal science","volume":"23 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145847364","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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