Center for Reproductive Medicine, the Fourth Hospital of Shijiazhuang (Gynecology and Obstetrics Hospital Affiliated to Hebei Medical University), Key Laboratory of Maternal and Fetal Medicine of Hebei Province, Shijiazhuang 050011, Hebei, China; The institute of Reproductive Health and Infertility, Shijiazhuang 050011, Hebei, China.
Center for Reproductive Medicine, the Fourth Hospital of Shijiazhuang (Gynecology and Obstetrics Hospital Affiliated to Hebei Medical University), Key Laboratory of Maternal and Fetal Medicine of Hebei Province, Shijiazhuang 050011, Hebei, China; The institute of Reproductive Health and Infertility, Shijiazhuang 050011, Hebei, China.
J Reprod Immunol. 2022 Aug;152:103638. doi: 10.1016/j.jri.2022.103638. Epub 2022 May 12.
Polycystic ovary syndrome (PCOS) is a common endocrine disorder and the leading cause of anovulatory infertility in women of reproductive age. Chronic low-grade inflammation is considered to be the major contributors to ovarian dysfunction. Human umbilical mesenchymal stem cell-derived exosomes (hUC-MSC-exos) have been proven to exhibit highly effective anti-inflammatory ability. However, its ability to protect against inflammatory response in PCOS remains unclear. Therefore, the aim of the present study was to explore the effect and underlying mechanisms of hUC-MSC-exos on inflammatory response of ovarian granulosa cells (GCs) in PCOS. In this study, we demonstrated that hUC-MSC-exos enhanced the expression of anti-inflammatory factor IL-10 and inhibited the expression of pro-inflammatory factors TNF-α and IFN-γ. Moreover, hUC-MSC-exos had the effects of inhibiting apoptosis and promoting progesterone production. Mechanistically, exposure to hUC-MSC-exos inhibited NF-κB signaling through significantly decreased the levels of the phosphorylation IκB and p65 in GCs. Moreover, the nuclear translocation of p65 was inhibited. Taken together, these results indicate that hUC-MSC-exos ameliorates the inflammation of granulosa cells in patients with PCOS by inhibiting NF-κB signaling pathway.
多囊卵巢综合征（PCOS）是一种常见的内分泌疾病，也是育龄妇女排卵障碍性不孕的主要原因。慢性低度炎症被认为是卵巢功能障碍的主要原因。人脐带间充质干细胞来源的外泌体（hUC-MSC-exos）已被证明具有高效的抗炎能力。然而，其在 PCOS 中对抗炎症反应的能力尚不清楚。因此，本研究旨在探讨 hUC-MSC-exos 对 PCOS 患者卵巢颗粒细胞（GCs）炎症反应的作用及潜在机制。在这项研究中，我们证明了 hUC-MSC-exos 增强了抗炎因子 IL-10 的表达，抑制了促炎因子 TNF-α 和 IFN-γ 的表达。此外，hUC-MSC-exos 具有抑制细胞凋亡和促进孕激素产生的作用。在机制上，hUC-MSC-exos 通过显著降低 GCs 中磷酸化 IκB 和 p65 的水平来抑制 NF-κB 信号通路。此外，还抑制了 p65 的核转位。综上所述，这些结果表明 hUC-MSC-exos 通过抑制 NF-κB 信号通路改善了 PCOS 患者颗粒细胞的炎症。
