Abstract
Background Atresia and degeneration,a follicular developmental fate that reduces female fertility and is trig-gered by granulosa cell(GC)apoptosis,have been induced by dozens of miRNAs.Here,we report a miRNA,miR-423,that inhibits the initiation of follicular atresia(FA),and early apoptosis of GCs.Results We showed that miR-423 was down-regulated during sow FA,and its levels in follicles were negatively cor-related with the GC density and the P4/E2 ratio in the follicular fluid in vivo.The in vitro gain-of-function experiments revealed that miR-423 suppresses cell apoptosis,especially early apoptosis in GCs.Mechanically speaking,the miR-423 targets and interacts with the 3'-UTR of the porcine SMAD7 gene,which encodes an apoptosis-inducing factor in GCs,and represses its expression and pro-apoptotic function.Interestingly,FA and the GC apoptosis-related IncRNA NORHA was demonstrated as a ceRNA of miR-423.Additionally,we showed that a single base deletion/insertion in the miR-423 promoter is significantly associated with the number of stillbirths(NSB)trait of sows.Conclusion These results demonstrate that miR-423 is a small molecule for inhibiting FA initiation and GC early apop-tosis,suggesting that treating with miR-423 may be a novel approach for inhibiting FA initiation and improving female fertility.
基金项目
国家重点研发计划(2022YFD1600903)
国家自然科学基金(32072693)
College Students'Innovative Entrepreneurial Training Plan Program(202110307028)
国家科技期刊平台
NSTL
万方数据