Yoo Masae, Tanaka Tomohito, Konishi Hiromi, Tanabe Akiko, Taniguchi Kohei, Komura Kazumasa, Hayashi Masami, Ohmichi Masahide
Department of Obstetrics and Gynecology.
Translational Research Program, Osaka Medical College, Takatsuki, Japan.
Onco Targets Ther. 2020 Apr 8;13:2987-2995. doi: 10.2147/OTT.S242703. eCollection 2020.
Cyclophosphamide, which is widely used to treat malignant disease, causes ovarian follicular atresia, which leads to premature ovarian insufficiency. The present study evaluated the protective effect of testosterone in preventing the decline in the ovarian reserve during cyclophosphamide treatment.
Using the COV434 human granulosa cell line, the protective effect of testosterone against cyclophosphamide was evaluated by immunocytochemistry, Western blotting and an MTS assay. The follicles in mouse ovaries and serum anti-Mullerian hormone were also assessed to evaluate the effects of testosterone.
Testosterone suppressed the decrease in cell viability and apoptosis caused by cyclophosphamide treatment in vitro. In vivo, the number of atretic follicles in the mouse ovary was significantly lower in the testosterone plus cyclophosphamide group than in the cyclophosphamide alone group (p=0.03). The serum anti-Mullerian hormone was significantly higher in the testosterone plus cyclophosphamide group than in the cyclophosphamide alone group (16.2 [9.7-22.6]) vs 11.2 [8.9-12.1], p<0.01). The rate of cleaved Caspase-3 expression in the testosterone plus cyclophosphamide group was lower than that in the cyclophosphamide alone group (28.4% vs 48.6%, p=0.03).
These findings indicated that testosterone has the potential to prevent ovarian damage induced by cyclophosphamide by protecting granulosa cells from cyclophosphamide-induced apoptosis.
环磷酰胺被广泛用于治疗恶性疾病，它会导致卵巢卵泡闭锁，进而引发卵巢早衰。本研究评估了睾酮在预防环磷酰胺治疗期间卵巢储备功能下降方面的保护作用。
使用COV434人颗粒细胞系，通过免疫细胞化学、蛋白质印迹法和MTS检测评估睾酮对环磷酰胺的保护作用。还评估了小鼠卵巢中的卵泡和血清抗苗勒管激素，以评价睾酮的作用。
在体外，睾酮可抑制环磷酰胺处理导致的细胞活力下降和细胞凋亡。在体内，睾酮加环磷酰胺组小鼠卵巢中闭锁卵泡的数量显著低于单独使用环磷酰胺组（p = 0.03）。睾酮加环磷酰胺组的血清抗苗勒管激素显著高于单独使用环磷酰胺组（16.2 [9.7 - 22.6] 对比 11.2 [8.9 - 12.1]，p < 0.01）。睾酮加环磷酰胺组中裂解的半胱天冬酶 - 3表达率低于单独使用环磷酰胺组（28.4% 对比 48.6%，p = 0.03）。
这些发现表明，睾酮有可能通过保护颗粒细胞免受环磷酰胺诱导的凋亡来预防环磷酰胺所致的卵巢损伤。
