Human umbilical cord mesenchymal stem cell-derived exosomes inhibit ovarian granulosa cells inflammatory response through inhibition of NF-κB signaling in polycystic ovary syndrome

Abstract

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.