Pigment Epithelial-Derived Factor (PEDF) Treatment Restores the Inflammatory and Angiogenic Balance in Ovaries of PCOS Mice

Polycystic ovary syndrome (PCOS) is the most common cause of female infertility. Hyperandrogenism, chronic inflammation and follicular hyper-vascularization are considered hallmarks of PCOS. We have shown that PEDF, a potent anti-angiogenic and anti-inflammatory factor, restores the impaired angiogenic and inflammatory balance, which governs ovarian hyperstimulation syndrome pathogenesis. Moreover, our in-vitro PCOS model data showed that DHT increased IL6/8 level in human granulosa cells (GC). Our objective was to evaluate the role of PEDF in the in-vivo PCOS mouse model and its therapeutic potential.

PCOS mice model was established by prenatal treatment of pregnant female mice with DHT resulted in PCOS-like female offspring; gene analysis was done by qPCR.

Gene analysis of primary GC (pGC) showed that the levels of IL6 and VEGF in PCOS-induced mice were higher than in control mice (P<0.05). rPEDF decreased the PCOS-induced excessive expression of IL6 and VEGF mRNA in pGC. There was no change in PEDF mRNA expression in pGC, yet, the ratios of PEDF\IL6 and PEDF\VEGF were significantly lower in PCOS compared to PCOS+rPEDF group (P<0.05). Vaginal opening in recombinant PEDF (rPEDF)–treated PCOS-induced mice, occurred significantly earlier than in non-treated PCOS-induced mice (P<0.05).

Our results suggest that intra-follicular impaired androgens, angiogenic-factors, cytokine and PEDF ovarian balance likely comprise a local regulatory loop, which disturbs GC genes expression in PCOS; which may be reversed by rPEDF treatment. Understanding the precise anti-angiogenic and anti-inflammatory mechanisms of PEDF in the PCOS may enable new therapeutic avenues for fertility and gynecological syndromes.