Abstract
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women. Previous studies have demonstrated the therapeutic efficacy of human bone marrow mesenchymal stem cells (BM-hMSCs) for PCOS; however, the regulatory mechanism remains unknown. Bone morphogenetic proteins (BMPs) secreted by BM-hMSCs may underlie the therapeutic effect of these cells on PCOS, based on the ability of BMPs to modulate androgen production and alter steroidogenesis pathway enzymes. In this study, we analyze the effect of BMP-2 on androgen production and steroidogenic pathway enzymes in H295R cells as a human PCOS in vitro cell model. In H295R cells, BMP-2 significantly suppressed cell proliferation, androgen production, and expression of androgen-synthesizing genes, as well as inflammatory gene expression. Furthermore, H295R cells treated with the BM-hMSCs secretome in the presence of neutralizing BMP-2 antibody or with BMP-2 gene knockdown showed augmented expression of androgen-producing genes. Taken together, these results indicate that BMP-2 is a key player mediating the favorable effects of the BM-hMSCs secretome in a human PCOS cell model. BMP-2 overexpression could increase the efficacy of BM-hMSC-based therapy, serving as a novel stem cell therapy for patients with intractable PCOS.
Highlights
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women, affecting 4–18% of reproductive-age women [1]
Theca cell hyperplasia is a major finding in patients with PCOS and contributes to ovarian androgen oversecretion [2,47,48]; we evaluated the ability of Bone morphogenetic proteins (BMPs)-2 to inhibit the proliferation of H295R cells in vitro
We found that BMP-2 inhibits cell proliferation and apoptosis gene expression in the H295R cell line as an in vitro model of PCOS
Summary
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women, affecting 4–18% of reproductive-age women [1]. PCOS is characterized by chronic lowgrade inflammation and hyperandrogenism caused by excess androgen synthesis by ovarian theca cells [2,3]. Women with PCOS have a greater risk of developing comorbidities later in life, such as type 2 diabetes, cardiovascular diseases, and uterine cancer [4,5,6]. The interaction between ovarian inflammation and altered ovarian androgen synthesis in PCOS may lead to insulin resistance [7,8]. Inhibition of inflammatory pathways has been shown to reverse PCOS-induced hyperandrogenemia [12]
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