Farnesyl Diphosphate Synthase (FDPS) Regulates Granulosa Cells Proliferation of Polycystic Ovary Syndrome (PCOS) by Modulating the Rac1/MAPK/ERK signaling

Abstract

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in child-bearing-age women. Due to a poor understanding of the mechanisms involved, there is a limited selection of etiology-specific treatments for infertility in individuals with PCOS. Here, proteomic analysis indicated that the differential protein ovarian Farnesyl Diphosphate Synthase (FDPS) was closely related to the pathogenesis of PCOS. Notably, FDPS protein expression was significantly decreased in ovarian granulosa cells from PCOS patients resulted in disrupted ovarian functions and dysplasia of ovarian granulosa cells. The mechanisms by which FDPS affected the proliferation of granulosa cells were also explored both in vitro and in vivo. We found that knockdown of FDPS inhibited the proliferation of KGN (human ovarian granulosa cell line), while overexpression of FDPS had the opposite effect. FDPS activated Rac1 activity and regulated MAPK/ERK signaling pathway, which affecting the proliferation of KGN cells significantly. In addition, treatment with the Adeno-Associated Virus (AAV)-FDPS reverse the DHEA-induced PCOS-phenotype in mice. Our data indicated that FDPS could regulate the proliferation of ovarian GCs by modulating MAPK/ERK pathway via activating Rac1 activity. These findings suggest that FDPS could be of great value for the regulation of ovarian granulosa cell function and the treatment of PCOS.