Sirtuin 7 is essential for the survival and synthesis of estrogen in Yak (Bos grunniens) cumulus granulosa cells

Cumulus granulosa cells (CGCs) are a type of important ovarian somatic cells that carries out various functions related to oogenesis, follicular development and embryogenesis. The study on the development and function of CGCs facilitates the understanding of reproductive regulation in female Animals. Sirtuin 7 (SIRT7) is a member of the Sirtuin family of NAD+-dependent deacetylases mediating numerous biological processes. In this study, we detected the localization of SIRT7 in yak ovaries as well as explored the function of SIRT7 in yak CGCs. The results revealed that the SIRT7 protein was mainly localized in the cytoplasm of oocytes，granulosa cells and theca cells. The knockdown of SIRT7 in yak CGCs repressed cell proliferation and impacted the expressions of several apoptosis-related genes. Furthermore, estrogen synthesis was also inhibited in SIRT7-deficient yak CGCs. The expressions of several sterogenesis-related genes decreased significantly following SIRT7 knockdown. In addition, the lack of SIRT7 in yak CGCs resulted in decreased levels of the TGFB/Smad Family members TGFB1, TGFBR1 SMAD2 and SMAD3. Moreover, the activation of the TGFB/SMAD pathway by adding TGFB/SMAD pathway activator SRI-011381 partially rescued the level of estrogen secreted by SIRT7-deficient yak CGCs, as well as the expressions of steroidogenesis-related genes NR5A1 and CYP19A1. This research is the first to focus on the role of SIRT7 in yak ovary and the outcomes offer new insights into the mechanism governing yak reproduction.

SIRT7; TGFB/SMAD pathway; cumulus granulosa cells; estrogen; yak.