Department of Reproductive Medicine, The First Affiliated Hospital, Jinan University, 601 West Huangpu Avenue, 510000, Guangzhou, People's Republic of China.
The Second Hospital, University of South China, 421001, Hengyang, People's Republic of China.
J Ovarian Res. 2021 Jan 18;14(1):15. doi: 10.1186/s13048-020-00755-z.
PCOS is a heterogeneous endocrine disorder with both reproductive and metabolic abnormalities. At present, PCOS has been confirmed to have a certain genetic background. Compared with healthy women, the vast majority of PCOS patients have hyperandrogenemia, and this excessive androgen exposure during pregnancy may affect the development of female fetuses. The aim of the current study was to investigate the effect of adiponectin intervention during early pregnancy of obese mice with PCOS on the metabolic phenotype of adult female offspring.
After the PCOS model was established, C57BL/6J mice were divided into maternal-control, maternal-PCOS, and maternal-PCOS + APN groups. DHEA-induced PCOS mice were supplemented with adiponectin (10 mg/kg/day) in the early pregnancy in order to eliminate adverse hormone exposure and then traced for endocrine indicators in their adult female offspring, which were observed for metabolism syndrome or endocrine disturbance and exhibited the main effects of APN. To further explore the underlying mechanism, the relative expressions of phosphorylated AMPK, PI3K, and Akt were detected in the ovaries of offspring mice.
The serum testosterone level of the maternal-PCOS + APN group in early pregnancy was significantly lower than that of the maternal-PCOS group (p < 0.01). The serum testosterone level in the offspring-PCOS + APN group was significantly lower than in the offspring-PCOS group (p <0.05), the diestrus time characterized by massive granulocyte aggregation in the estrus cycle was significantly shorter than in the offspring-PCOS group (p<0.05), and the phenotypes of PCOS-like reproductive disorders and metabolic disorders, such as obesity, insulin resistance, impaired glucose tolerance, and hyperlipidemia, were also significantly improved in the offspring-PCOS + APN group (p < 0.05). Compared with the control group, the expression levels of phosphorylated AMPK, PI3K, and Akt in the offspring-PCOS group were significantly decreased (p < 0.05), while those in the offspring-PCOS + APN group were significantly increased (p < 0.05).
APN intervention in early pregnancy significantly reduced the adverse effects of maternal obesity and high androgen levels during pregnancy on female offspring and corrected the PCOS-like endocrine phenotype and metabolic disorders of adult female offspring. This effect may be caused by the activation of the AMPK/PI3K-Akt signaling pathway in PCOS offspring mice.
多囊卵巢综合征（PCOS）是一种具有生殖和代谢异常的异质性内分泌疾病。目前，PCOS 已被证实具有一定的遗传背景。与健康女性相比，绝大多数 PCOS 患者存在高雄激素血症，而这种过量的雄激素暴露在妊娠期间可能会影响女性胎儿的发育。本研究旨在探讨 PCOS 肥胖小鼠妊娠早期脂联素（APN）干预对成年雌性后代代谢表型的影响。
建立 PCOS 模型后，将 C57BL/6J 小鼠分为母鼠对照、母鼠 PCOS 和母鼠 PCOS+APN 组。用脱氢表雄酮（DHEA）诱导 PCOS 小鼠，在妊娠早期补充脂联素（10mg/kg/天），以消除不良激素暴露，然后追踪其成年雌性后代的内分泌指标，观察代谢综合征或内分泌紊乱，并表现出 APN 的主要作用。为了进一步探讨其潜在机制，检测了子代小鼠卵巢中磷酸化 AMPK、PI3K 和 Akt 的相对表达水平。
妊娠早期母鼠 PCOS+APN 组血清睾酮水平明显低于母鼠 PCOS 组（p<0.01）。子代 PCOS+APN 组血清睾酮水平明显低于子代 PCOS 组（p<0.05），发情周期中以大量粒细胞聚集为特征的动情间期明显短于子代 PCOS 组（p<0.05），PCOS 样生殖障碍和代谢障碍的表型，如肥胖、胰岛素抵抗、糖耐量受损和高脂血症，在子代 PCOS+APN 组也明显改善（p<0.05）。与对照组相比，子代 PCOS 组磷酸化 AMPK、PI3K 和 Akt 的表达水平明显降低（p<0.05），而子代 PCOS+APN 组则明显升高（p<0.05）。
妊娠早期 APN 干预可显著减轻母鼠肥胖和妊娠期间高雄激素水平对雌性后代的不良影响，纠正成年雌性后代的 PCOS 样内分泌表型和代谢障碍。这种作用可能是通过激活 PCOS 子代小鼠的 AMPK/PI3K-Akt 信号通路。
