a Center for Reproductive Medicine , School of Medicine , Renji Hospital, Shanghai Jiao Tong University , Shanghai , PR China.
b Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics , Shanghai , PR China.
Gynecol Endocrinol. 2019 Aug;35(8):669-672. doi: 10.1080/09513590.2018.1540567. Epub 2019 May 6.
Hyperandrogenism is one of the most common causes for anovulation in women and increases the risk for metabolic disorder in PCOS patients. Autophagy plays an important role in dysfunction of endocrine and anovulation. However, the relationship between hyperandrogenism and autophagy in human granulosa cells of PCOS patients remains unclear. By collecting granulosa cells from PCOS patients and non-PCOS patients, we found that the abundance of autophagy-related genes ATG5, ATG7, BECN1 mRNA and the ratio of autophagy marker protein light chain 3B II/I (LC3 II/I) were significantly increased whereas the abundance of the autophagy substrate SQSTM1/p62 was decreased in ovarian granulosa cells from PCOS patients. Furthermore, we demonstrated that BECN1 mRNA abundance in human granulosa cells positively correlated with the basal level of serum total testosterone and androgen up-regulated the abundance of BECN1 mRNA and the ratio of LC3II/LC3I in a dose-dependent manner in cultured granulosa cells. These observations indicated that androgen-induced activation of autophagy may play an important role in the development of PCOS and to explore the autophagy mechanisms involved in PCOS yield new insight into the pathophysiology and therapy of the disorder.
高雄激素血症是导致女性排卵障碍的最常见原因之一，并且会增加 PCOS 患者发生代谢紊乱的风险。自噬在激素分泌失调和排卵障碍中发挥着重要作用。然而，高雄激素血症与 PCOS 患者的人卵巢颗粒细胞自噬之间的关系尚不清楚。通过收集 PCOS 患者和非 PCOS 患者的颗粒细胞，我们发现 PCOS 患者卵巢颗粒细胞中自噬相关基因 ATG5、ATG7、BECN1mRNA 的丰度以及自噬标志物蛋白 LC3B II/I（LC3 II/I）的比值明显增加，而自噬底物 SQSTM1/p62 的丰度降低。此外，我们证明人卵巢颗粒细胞中 BECN1mRNA 的丰度与血清总睾酮的基础水平呈正相关，并且雄激素以剂量依赖性方式上调培养的颗粒细胞中 BECN1mRNA 的丰度和 LC3II/LC3I 的比值。这些观察结果表明，雄激素诱导的自噬激活可能在 PCOS 的发生发展中起重要作用，探索 PCOS 相关的自噬机制为该疾病的病理生理学和治疗提供了新的见解。
