Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, 639 Zhizaoju road, Shanghai, 200000, China.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanxi Midical University, 56 Xinjian South Road, Taiyuan, Shanxi Province, 030002, China.
Sci Rep. 2018 Mar 13;8(1):4439. doi: 10.1038/s41598-018-22797-6.
Medroxyprogesterone 17-acetate (MPA) combined with human menopausal gonadotropin (hMG) has been effectively used for ovarian stimulation in clinical practice. However, the molecular mechanism of MPA + hMG treatment in follicular development is poorly described. Here we performed a study to investigate the impact of MPA + hMG on ovarian stimulation utilizing a mouse model in vivo. Forty female BALB/C mice were randomly divided into four groups of 10 each and treated during ciestrus stage and continued for 5 days: control group, MPA group, hMG group, and MPA + hMG group. Morphological and molecular biology methods were used for detecting serum hormones and ovarian function. MPA + hMG group exhibited increasing follicle stimulating hormone (FSH), antral follicle, FSH receptor (FSHR) and phosphorylated mammal target of rapamycin (p-mTOR), and decreasing luteinizing hormone (LH), estradiol (E2), progesterone (P), corpus luteum, phosphoinositide 3-kinase (PI3K), Akt and mTOR compared with control group. In contrast, MPA + hMG group showed reduced FSH, LH, E2, P, corpus luteum, LH receptor (LHR), and activated PI3K,/Akt/mTOR pathway compared with hMG group (P < 0.05). Collectively, these data definitively established that MPA plus hMG may modulate the hormone, hormone receptor and PI3K/Akt/mTOR signaling pathway to influence follicular development in the mouse ovary. Our study provides overwhelming support for MPA + hMG as an effective treatment for infertility in women.
醋酸甲羟孕酮（MPA）联合人绝经期促性腺激素（hMG）已在临床实践中有效地用于卵巢刺激。然而，MPA+hMG 治疗在卵泡发育中的分子机制描述甚少。在这里，我们利用体内小鼠模型研究了 MPA+hMG 对卵巢刺激的影响。40 只雌性 BALB/C 小鼠被随机分为 4 组，每组 10 只，并在动情期进行处理，持续 5 天：对照组、MPA 组、hMG 组和 MPA+hMG 组。采用形态学和分子生物学方法检测血清激素和卵巢功能。与对照组相比，MPA+hMG 组表现为卵泡刺激素（FSH）、窦卵泡、FSH 受体（FSHR）和磷酸化哺乳动物雷帕霉素靶蛋白（p-mTOR）增加，而黄体生成素（LH）、雌二醇（E2）、孕酮（P）、黄体、磷酸肌醇 3-激酶（PI3K）、Akt 和 mTOR 减少。相反，与 hMG 组相比，MPA+hMG 组 FSH、LH、E2、P、黄体、LH 受体（LHR）和激活的 PI3K/Akt/mTOR 通路减少（P<0.05）。综上所述，这些数据明确表明 MPA 加 hMG 可能通过调节激素、激素受体和 PI3K/Akt/mTOR 信号通路来影响小鼠卵巢中的卵泡发育。我们的研究为 MPA+hMG 作为女性不孕的有效治疗方法提供了有力支持。
