Mesenchymal Stem Cells Alleviate DHEA-Induced Polycystic Ovary Syndrome (PCOS) by Inhibiting Inflammation in Mice

Abstract

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of reproductive age. Chronic inflammation is considered to be the cause of ovarian dysfunction. Increasing evidence in animal studies and in preliminary clinical trials has demonstrated that MSCs possess immunomodulatory effects via their interaction with immune cells. However, their contribution to PCOS remains unclear. In this study, we showed that the administration of hUC-MSCs could efficiently improve the pathological changes of PCOS mice induced by dehydroepiandrosterone (DHEA), including ovarian histopathology and function. Moreover, we found that the administration of MSCs significantly downregulated the expression of proinflammatory factors (TNF-α, IL-1β, and IFN-γ) and fibrosis-related genes (CTGF) in ovarian and uterus tissues and affected the systemic inflammatory response. The percentage of peripheral neutrophils, M1 macrophages, and B cells was significantly reduced, while M2 macrophages and regulatory T cells (Tregs) were increased in hUC-MSC-treated mice. In the spleen, the percentage of neutrophils, M1 macrophages, IFN-γ+CD19+B cell, IFN-γ+CD4+T cells (Th1), and IL-17+CD4+T cells (Th17) was significantly decreased in hUC-MSC-treated mice. These results suggested that hUC-MSC treatment could alleviate ovarian dysfunction by inhibiting ovarian local and systemic inflammatory responses.

Mesenchymal Stem Cells as a Bio Organ for Treatment of Female Infertility

“…These effects seem to be related to pathways that induce regeneration and angiogenesis, which may also improve ovarian function. This potential mechanism of MSCs activity is of particular importance since these pathways can regulate immune responses and inflammation, improve injured tissues, and stimulate progenitor cells to different iate into specific-tissue cells (5,30). Here, review studies of the biology and clinical utility of MSCs from several different sources to treat female reproductive system disorders (Table 1).…”

“…Researchers found that UC-MSC transplantation restored ovarian function in dehydroepiandrosterone (DHEA)-induced PCOS in mice. This effect was mediated by downregulation of inflammatory cytokine expression, including interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ), as well as fibrosis-related genes such as connective tissue growth factor (CTGF) (30). While these studies suggest that UC-MSC transplantation may be helpful for controlling disorders related to the ovaries, more studies are needed to develop a valid US-MSC-based therapeutic approach.…”

Mesenchymal Stem Cells as a Bio Organ for Treatment of Female Infertility

“…These effects seem to be related to pathways that induce regeneration and angiogenesis, which may also improve ovarian function. This potential mechanism of MSCs activity is of particular importance, since these pathways can regulate immune responses and inflammation, improve injured tissues, and stimulate progenitor cells to differentiate into specific tissue cells [ 5 , 36 ].…”

“…Researchers found that UC-MSC transplantation restored ovarian function in dehydroepiandrosterone (DHEA)-induced PCOS in mice. This effect was mediated by the downregulation of inflammatory cytokine expression, including interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ), as well as fibrosis-related genes such as connective tissue growth factor (CTGF) [ 36 ]. While these studies suggest that UC-MSC transplantation may be helpful for controlling disorders related to the ovaries, more studies are needed to develop a valid US-MSC‒based therapeutic approach.…”

Identification of the Active Constituents and Significant Pathways of Cangfu Daotan Decoction for the Treatment of PCOS Based on Network Pharmacology

“…AGE-RAGE signalling may activate multiple intracellular signalling pathways involving protein kinase C and MAPKs and may influence NF-κB activity. Research has shown an association between PCOS and chronic inflammatory factors, proinflammatory cytokines such as interleukin-1, interleukin-6, interleukin-17 [41][42][43], and tumour necrosis-α, and a variety of inflammationrelated genes, including VEGF, tissue factor, and RAGE [44,45].…”