Effects of Mitochondrial Uncoupling Protein 2 Inhibition by Genipin in Human Cumulus Cells.

Hongshan Ge,Dan Shan,Chunfang Zhu,Jeiqiang Lv,Jianying Huang,Haitao Xi,Xiaona Wang,Chao Ling,Fan Zhang,Hua Chen

doi:10.1155/2015/323246

Abstract

UCP2 plays a physiological role by regulating mitochondrial biogenesis, maintaining energy balance, ROS elimination, and regulating cellular autophagy in numerous tissues. But the exact roles of UCP2 in cumulus cells are still not clear. Genipin, a special UCP2 inhibitor, was added into the cultural medium to explore the roles of UCP2 in human cumulus cells. There were no significant differences in ATP and mitochondrial membrane potential levels in cumulus cells from UCP2 inhibiting groups as compared with the control. The levels of ROS and Mn-SOD were markedly elevated after UCP2 inhibited Genipin. However, the ratio of reduced GSH to GSSG significantly declined after treatment with Genipin. UCP2 inhibition by Genipin also resulted in obvious increase in the active caspase-3, which accompanied the decline of caspase-3 mRNA. The level of progesterone in culture medium declined obviously after Genipin treatment. But there was no significant difference in estradiol concentrations. This study indicated that UCP2 is expressed in human cumulus cells and plays important roles on mediate ROS production, apoptotic process, and steroidogenesis, suggesting UCP2 may be involved in regulation of follicle development and oocyte maturation and quality.

Highlights

Mammalian ovarian follicles are highly specialized structures that support the growth and development of oocytes
A CCK8 assay was used to determine the appropriate concentration of Genipin choice in the study, which would not result in significant cytotoxicity on cumulus cells (CCs)
Numerous researches observed that uncoupling protein 2 (UCP2) plays key roles in regulation of ATP production and maintaining cellular energy balance

Summary

Introduction

Mammalian ovarian follicles are highly specialized structures that support the growth and development of oocytes. The mural granulosa cells, located in the basal membrane of the follicles, keep in lesser close contact with oocyte due to the distance. CCs are closer to the oocyte and maintain a proximity relationship via transzonal processes and gap junctions with the oocyte, providing nutrients, maturation-enabling factors, and an optimal microenvironment to ensure successful maturation and further developmental competence [2, 3]. This close relationship between the oocyte and CCs implies that the CCs may serve as a biomarker for oocyte maturation and quality [4]

Methods

Results

Conclusion