Background Undernutrition disrupts pregnant ewe's metabolic homeostasis and severely inhibits fetal growth and development.In this study,undernourished and nutrition-recovery pregnant sheep models and rumen epithe...Background Undernutrition disrupts pregnant ewe's metabolic homeostasis and severely inhibits fetal growth and development.In this study,undernourished and nutrition-recovery pregnant sheep models and rumen epithelial cells were utilized to investigate the mechanisms behind undernutrition-induced disruptions in male fetal rumen metabolism and development.Results Maternal undernutrition significantly reduced male fetal rumen weight and papilla length,width and surface area.Maternal undernutrition extremely suppressed nutrient metabolism and energy production in male fetal rumen via JAK3/STAT3 signaling to inhibit cell cycle progression and male fetal rumen development,while maternal nutritional recovery partially restored metabolic inhibition but failed to alleviate male fetal rumen development.Meanwhile,64 differentially expressed miRNAs(DEMs)were identified in male fetal rumen between undernourished ewes and controls.Novel miR-736 was overexpressed both in male fetal rumen of undernourished and nutrition-recovery models.E2F transcription factor 2(E2F2)and MYB proto-oncogene like 2(MYBL2)were the intersection of male fetal rumen differentially expressed genes(DEGs)and DEMs target genes integrated analysis and were predicted as novel miR-736 target genes.Further,we confirmed that novel miR-736 targeted and downregulated E2F2 and MYBL2 expression levels.Silencing E2F2 and MYBL2 promoted apoptosis and inhibited S-phase entry in rumen epithelial cells.Conclusions In summary,maternal undernutrition disrupted male fetal rumen metabolism and elevated novel miR-736,which targeted and downregulated E2F2 and MYBL2 to inhibit cell cycle progression and promote apoptosis,finally inhibited male fetal rumen development.This study provides new insights into the epigenetic mechanisms underlying maternal undernutrition-induced male fetal rumen developmental deficits.展开更多
基金supported by the National Natural Science Foundation of China(32402767)National Key Research and Development Program of China(2022YFD1301102)+3 种基金Anhui Province Natural Science Foundation Youth Project(2308085QC104)AAU Introduction of High-level Talent Funds(RC392107)Key Laboratory of Utilization of Livestock and Forage Resources in Circum-Tarim Region(Co-construction by Ministry and Province),Ministry of Agriculture and Rural Affairs(BSGJSYS202502)the China Agriculture Research System(CARS-38)。
文摘Background Undernutrition disrupts pregnant ewe's metabolic homeostasis and severely inhibits fetal growth and development.In this study,undernourished and nutrition-recovery pregnant sheep models and rumen epithelial cells were utilized to investigate the mechanisms behind undernutrition-induced disruptions in male fetal rumen metabolism and development.Results Maternal undernutrition significantly reduced male fetal rumen weight and papilla length,width and surface area.Maternal undernutrition extremely suppressed nutrient metabolism and energy production in male fetal rumen via JAK3/STAT3 signaling to inhibit cell cycle progression and male fetal rumen development,while maternal nutritional recovery partially restored metabolic inhibition but failed to alleviate male fetal rumen development.Meanwhile,64 differentially expressed miRNAs(DEMs)were identified in male fetal rumen between undernourished ewes and controls.Novel miR-736 was overexpressed both in male fetal rumen of undernourished and nutrition-recovery models.E2F transcription factor 2(E2F2)and MYB proto-oncogene like 2(MYBL2)were the intersection of male fetal rumen differentially expressed genes(DEGs)and DEMs target genes integrated analysis and were predicted as novel miR-736 target genes.Further,we confirmed that novel miR-736 targeted and downregulated E2F2 and MYBL2 expression levels.Silencing E2F2 and MYBL2 promoted apoptosis and inhibited S-phase entry in rumen epithelial cells.Conclusions In summary,maternal undernutrition disrupted male fetal rumen metabolism and elevated novel miR-736,which targeted and downregulated E2F2 and MYBL2 to inhibit cell cycle progression and promote apoptosis,finally inhibited male fetal rumen development.This study provides new insights into the epigenetic mechanisms underlying maternal undernutrition-induced male fetal rumen developmental deficits.
