Effects of Coenzyme Q10 on Ovarian Surface Epithelium-derived Ovarian Stem Cells and Ovarian Function in 4-vinylcyclohexene Diepoxide-induced Ovarian Failure Mice.

Abstract

Background: Several studies have shown that CoQ10 can rescue ovarian aging and that ovarian surface epithelium (OSE)-derived ovarian stem cells (OSCs) are useful for treating infertility with ovarian aging. However, there are few studies the effect of CoQ10 on OSCs. This study was aimed to investigate whether CoQ10 activates OSCs while recovering ovarian function using 4-vinylcyclohexene diepoxide (VCD)-induced ovarian failure mouse model.Methods: C57BL/6 female mice aged 6 weeks were randomly divided into four groups (n=10/group): (Control) saline and orally, (CoQ10) 150 mg/kg/day orally in 1 mL of saline daily for 14 days, (VCD) 160 mg/kg/day, 2.5 ml/kg ip for 5 days, (VCD+CoQ10) 5 days after VCD injection, CoQ10 (150 mg/kg/day) orally for 14 days. After final treatment of CoQ10, follicle counts were evaluated by hematoxylin and eosin (H&E) staining, and ovarian mRNA expressions of Bmp-15, Gdf-9, and c-Kit were examined by quantitative real-time PCR. Serum FSH, AMH, and ROS levels were also measured. Oocyte-like structure count and expression of Oct-4 and MVH were evaluated from postcultured OSE for 3 weeks. In the second experiment, another 32 female mice were administered with CoQ10 in the same way as above and were superovulated by PMSG and hCG, followed by mated with males. Then, numbers of zygotes ovulated and embryo development rate were examined. Results: Postcultured OSE had significantly increased numbers of oocyte-like structure and expression of Oct-4 and MVH in VCD+CoQ10 group compared to VCD group (p <0.05). Numbers of surviving follicles including from primordial to antral follicles, numbers of zygotes retrieved and embryo development rate to blastocyst were significantly higher in VCD+CoQ10 group compared to VCD group (p <0.01). Serum AMH level and ovarian expression of Bmp-15, Gdf-9, and c-Kit were significantly increased in VCD+CoQ10 group compared to VCD group (p <0.05). In contrast, serum ROS level was significantly decreased in VCD+CoQ10 group compared to VCD group (p <0.05). Conclusion(s): This is the first study to show that CoQ10 stimulates the differentiation of OSE-derived OSCs. Also this study confirms that CoQ10 can reduce ROS levels, leading to improve ovarian function and oocyte quality in ovarian failure mice.

Influence of Systemic Administration of Coq10 Nanoparticles on Ischemia-Reperfusion Injury on Ovaries in Rat

“…e suppression of ROS by antioxidants reversibly inhibits the resumption of meiosis in rat oocytes in vitro. e probable mechanism underlining these effects of ROS is linked with the stimulation of 5′ adenosine monophosphate-activated protein kinase (AMPK) and/or the Ca2+-mediated pathway that induces meiotic resumption from diplotene arrest in mammalian oocytes [13]. Overproduction of ROS can affect the in vitro culture of preantral follicles because they can act as second messengers and lead to the opening of a nonspecific pore in the inner mitochondrial membrane, release of cytochrome c, and activation of caspase cascades ultimately resulting in apoptosis.…”

“…Excessive production of reactive oxygen species can influence the in vitro culture of preantral follicles because they can act as second messengers and result in the opening of a nonspecific pore in the inner mitochondrial membrane, release of cytochrome c, and activation of caspase cascades ultimately resulting in apoptosis. Although excessive production of oxidative agents can cause cell damage and loss of follicular function, antioxidants can attenuate deleterious effects of oxidative stress [12,13].…”