Neuromedin S Regulates Steroidogenesis through Maintaining Mitochondrial Morphology and Function via NMUR2 in Goat Ovarian Granulosa Cells

Abstract

Neuromedin S (NMS) plays various roles in reproductive regulation, while the mechanism by which NMS regulates ovarian steroidogenesis remains unclear. In the current study, we confirmed the enhancement role of NMS in steroidogenesis in goat ovarian granulosa cells (GCs). To further explore the specific mechanism, we conducted a knockdown of NMUR2 in GCs followed by treatment with NMS and determined the effects of NMS treatment on mitochondrial morphology and function. The results found that NMS treatment increased the production of estrogen and up-regulated the expression of STAR, CYP11A1, 3BHSD, and CYP19A1, while the effects of NMS treatment were blocked by the knockdown of NMUR2 in goat GCs. Moreover, NMS treatment enhanced the fusion of mitochondria and up-regulated the expression of OPA1, MFN1, and MFN2, and increased mitochondrial membrane potential, the activity of respiratory chain enzymes and ATP production by maintaining a low expression level of mitochondrial unfolded protein response markers. The effects of NMS treatment on mitochondria were reversed by NMUR2 knockdown and NMS cotreatment. The possible mechanism of the results above was revealed by NMS treatment activating the Hippo pathway effector YAP1 and then managing the expression of phosphorylation PPARGC1A (Ser571). Together, these data showed that NMS promoted the fusion of mitochondria and protected mitochondrial function from mitochondrial unfolded protein response possibly via the NMUR2/YAP1/PPARGC1A pathway, thereby affecting the steroidogenesis of goat GCs. By elaborating the potential mechanism of NMS in regulating estrogen production in goat GCs, our results can serve as the mechanism reference for follicular growth and development.