辅酶 Q10 对 4-乙烯环己烯二恶烷诱导的卵巢早衰小鼠模型中卵巢表面上皮来源的卵巢干细胞和卵巢功能的影响。
Effects of coenzyme Q10 on ovarian surface epithelium-derived ovarian stem cells and ovarian function in a 4-vinylcyclohexene diepoxide-induced murine model of ovarian failure.
机构信息
Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Busan, Republic of Korea.
Biomedical Research Institute, Pusan National University Hospital, Busan, 49241, Republic of Korea.
出版信息
Reprod Biol Endocrinol. 2021 Apr 22;19(1):59. doi: 10.1186/s12958-021-00736-x.
BACKGROUND
Several studies have shown that coenzyme Q10 (CoQ10) can rescue ovarian aging and that ovarian surface epithelium (OSE)-derived ovarian stem cells (OSCs) are useful for treating infertility due to ovarian aging. However, few studies have examined the effect of CoQ10 on OSCs. This study was aimed to investigate whether CoQ10 activates OSCs and recovers ovarian function in a 4-vinylcyclohexene diepoxide (VCD)-induced mouse model of ovarian failure.
METHODS
Forty female C57BL/6 mice aged 6 weeks were randomly divided into four groups (n = 10/group): a control group administered saline orally, a CoQ10 group administered 150 mg/kg/day of CoQ10 orally in 1 mL of saline daily for 14 days, a VCD group administered 160 mg/kg/day of VCD i.p. in 2.5 mL of saline/kg for 5 days, and a VCD + CoQ10 group administered VCD i.p. for 5 days injection and CoQ10 (150 mg/kg/day) orally for 14 days. After treatment, 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 counts and the expressions of Oct-4 and MVH were also evaluated after culturing OSE for 3 weeks. In a second experiment, 32 female mice were administered CoQ10 as described above, induced to superovulate using PMSG and hCG, and mated. Numbers of zygotes and embryo development rate were examined.
RESULTS
Postcultured OSE showed significant increases in the numbers of oocyte-like structure and that the expression of Oct-4 and MVH were higher in the VCD + CoQ10 group than in the VCD group (p < 0.05). Numbers of surviving follicles from primordial to antral follicles, numbers of zygotes retrieved and embryo development rate to blastocyst were significantly greater in the VCD + CoQ10 group than in the VCD group (p < 0.01). Serum AMH level and ovarian expressions of Bmp-15, Gdf-9 and c-Kit were also significantly greater in the VCD + CoQ10 group than in the VCD group (p < 0.05). In contrast, serum ROS level was significantly lower in the VCD + CoQ10 group than in the VCD group (p < 0.05).
CONCLUSION
This study shows that CoQ10 stimulates the differentiation of OSE-derived OSCs and confirms that CoQ10 can reduce ROS levels and improve ovarian function and oocyte quality in mice with VCD-induced ovarian failure.
背景
多项研究表明，辅酶 Q10（CoQ10）可以挽救卵巢衰老，卵巢表面上皮（OSE）衍生的卵巢干细胞（OSCs）可用于治疗因卵巢衰老引起的不孕。然而，很少有研究探讨 CoQ10 对 OSCs 的影响。本研究旨在探讨 CoQ10 是否能激活 OSCs 并恢复 4-乙烯环己烯二氧化物（VCD）诱导的卵巢衰竭小鼠模型的卵巢功能。
方法
40 只 6 周龄 C57BL/6 雌性小鼠被随机分为四组（n=10/组）：对照组给予生理盐水灌胃；CoQ10 组给予 CoQ10（150mg/kg/天），溶于 1mL 生理盐水，每天 1 次，连续 14 天；VCD 组给予 VCD（160mg/kg/天）腹腔注射，溶于 2.5mL/kg 生理盐水，连续 5 天；VCD+CoQ10 组先给予 VCD 腹腔注射，连续 5 天，再给予 CoQ10（150mg/kg/天）灌胃，连续 14 天。治疗后，通过苏木精和伊红（H&E）染色评估卵泡计数，并通过定量实时 PCR 检测卵巢 Bmp-15、Gdf-9 和 c-Kit 的 mRNA 表达。还测量了血清 FSH、AMH 和 ROS 水平。培养 OSE 3 周后，还评估了卵母细胞样结构的计数以及 Oct-4 和 MVH 的表达。在第二个实验中，如前所述给予 32 只雌性小鼠 CoQ10，用 PMSG 和 hCG 诱导超排卵，并进行交配。检查受精卵和胚胎发育率。
结果
培养后的 OSE 卵母细胞样结构数量显著增加，VCD+CoQ10 组的 Oct-4 和 MVH 表达高于 VCD 组（p<0.05）。VCD+CoQ10 组的存活卵泡数（从原始卵泡到窦卵泡）、受精卵数和胚胎发育率（至囊胚）均显著高于 VCD 组（p<0.01）。VCD+CoQ10 组的血清 AMH 水平和卵巢 Bmp-15、Gdf-9 和 c-Kit 的表达也显著高于 VCD 组（p<0.05）。相反，VCD+CoQ10 组的血清 ROS 水平显著低于 VCD 组（p<0.05）。
结论
本研究表明 CoQ10 可刺激 OSE 衍生的 OSCs 分化，并证实 CoQ10 可降低 ROS 水平，改善 VCD 诱导的卵巢衰竭小鼠的卵巢功能和卵母细胞质量。
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