MIR-361-5P Mediates TGF-β Signalling to Promote Granulosa Cell Apoptosis Through Vegfa During Porcine Follicle Atresia

Abstract Background: Follicular atresia is an inevitable degenerative process of ovarian follicles in mammals. The molecular events involved in atresia, particularly in granulosa cell apoptosis, have always attracted researchers’ attention. It is known that VEGFA isdownregulated during follicular atresia in pig ovaries and serves as an apoptosis inhibitor of granulosa cells. Besides, the TGF-β signalling has been considered as a central trigger in granulosa cell apoptosis. However, the link between TGF-β signalling and VEGFA is missing.Results:We proved that miR-361-5p significantly up-regulated during the atresia process andenhances GC apoptosis by direct targeting to VEGFA 3’UTR. In addition,we revealed that miR-361-5p coding geneMIR361was significant downregulation bySMAD4, the central intracellular mediator of TGF-β signalling,through promoter binding.Conclusions: Our findingsenriched the knowledge of VEGFA post-transcriptional regulation and completed the TGF-β/miR-361-5p/VEGFAregulatory networkin ovarian granulosa cell apoptosis. It offereduseful references for follicular atresia and ovarian physiological function studies.