College of Basic Medical Science, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian, China.
J Cell Physiol. 2019 May;234(5):7435-7447. doi: 10.1002/jcp.27501. Epub 2018 Dec 23.
Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in child-bearing-age women. It is characterized by ovulation dysfunction, polycystic ovaries, and hyperandrogenism. Inflammation is likely to be a crucial contributor to the pathogenesis of PCOS. However, the association between the inflammatory cytokines and the development of PCOS has not been reported. To explore the relationship between the inflammatory cytokines and PCOS, alterations of serum proteins in dehydroepiandrosterone (DHEA)-induced PCOS rats were screened by protein array, and the concentration of IFN-γ was further measured by using enzyme-linked immunosorbent assay (ELISA). DHEA-induced PCOS rats had a decreased level of IFN-γ compared with the control rats, which was restored partly in flutamide (an androgen receptor antagonist)-treated rats. Moreover, the level of IFN-γ in serum of patients with PCOS was also lower than that in healthy women. Using the ovarian granulosa cells (KGN), we demonstrated that DHEA downregulated the expression and secretion of IFN-γ in dose- and time-dependent manners, which could be restored to some extent by treating with flutamide. Furthermore, flutamide ameliorated the inhibitory effect on cell proliferation and promotive effect on cell apoptosis by DHEA. The results also revealed that IFN-γ promoted the proliferation but inhibited the apoptosis of KGN cells, which was suppressed by DHEA via activating the downstream PI3K/AKT signaling pathway. Taken together, these results showed that DHEA inhibited the proliferation and promoted the apoptosis of ovarian granulosa cells through downregulating the expression of IFN-γ which could be restored by flutamide, and IFN-γ may serve as a potential inflammatory biomarker for PCOS detection.
多囊卵巢综合征（PCOS）是育龄妇女不孕的最常见原因之一。其特征为排卵功能障碍、多囊卵巢和高雄激素血症。炎症可能是 PCOS 发病机制的关键因素。然而，炎症细胞因子与 PCOS 发展之间的关系尚未见报道。为了探讨炎症细胞因子与 PCOS 之间的关系，我们通过蛋白质芯片筛选脱氢表雄酮（DHEA）诱导的 PCOS 大鼠血清蛋白的变化，并通过酶联免疫吸附试验（ELISA）进一步测量 IFN-γ的浓度。与对照组大鼠相比，DHEA 诱导的 PCOS 大鼠 IFN-γ水平降低，而在雄激素受体拮抗剂氟他胺治疗的大鼠中部分恢复。此外，PCOS 患者血清中 IFN-γ水平也低于健康女性。我们使用卵巢颗粒细胞（KGN）证明，DHEA 以剂量和时间依赖的方式下调 IFN-γ的表达和分泌，而用氟他胺处理可在一定程度上恢复。此外，氟他胺改善了 DHEA 对细胞增殖的抑制作用和对细胞凋亡的促进作用。结果还表明，IFN-γ促进 KGN 细胞的增殖，但抑制细胞凋亡，而 DHEA 通过激活下游 PI3K/AKT 信号通路抑制其作用。综上所述，这些结果表明，DHEA 通过下调 IFN-γ的表达抑制卵巢颗粒细胞的增殖并促进其凋亡，而氟他胺可部分恢复这种作用，IFN-γ可能作为 PCOS 检测的潜在炎症生物标志物。
