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Effects of Mitochondrial Uncoupling Protein 2 Inhibition by Genipin in Human Cumulus Cells
Hongshan Ge1, Fan Zhang1, Dan Shan1
1Reproductive Health Center, Second Affiliated Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou, Zhejiang 325000, China.
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.
Insights
Uncoupling protein 2 (UCP2) in human cumulus cells regulates reactive oxygen species (ROS), apoptosis, and steroidogenesis, impacting follicle development and oocyte quality.
Area of Science:
- Reproductive Biology
- Cellular Physiology
- Mitochondrial Function
Background:
- Uncoupling protein 2 (UCP2) is vital for mitochondrial biogenesis, energy balance, ROS elimination, and autophagy in various tissues.
- The specific function of UCP2 in human cumulus cells remains largely undefined.
Purpose of the Study:
- To investigate the role of UCP2 in human cumulus cells using the UCP2 inhibitor Genipin.
- To elucidate UCP2's influence on cellular processes critical for oocyte quality.
Main Methods:
- Human cumulus cells were treated with Genipin, a specific UCP2 inhibitor.
- Assessed ATP levels, mitochondrial membrane potential, reactive oxygen species (ROS), Mn-SOD, GSH/GSSG ratio, and caspase-3 activity.
- Measured progesterone and estradiol concentrations in the culture medium.
Main Results:
- UCP2 inhibition did not alter ATP or mitochondrial membrane potential.
- Genipin treatment significantly increased ROS and Mn-SOD levels, while decreasing the GSH/GSSG ratio.
- Inhibition of UCP2 led to increased active caspase-3 and decreased progesterone, without affecting estradiol.
Conclusions:
- UCP2 is expressed in human cumulus cells and modulates ROS production, apoptosis, and steroidogenesis.
- These findings suggest UCP2's involvement in regulating follicle development and oocyte maturation/quality.
