The Metabolic Role of PEDF in the Polycystic Ovary Syndrome (PCOS)

Introduction: PCOS is a common syndrome associated with obesity and insulin resistance (IR), which are components of the metabolic syndrome. A group of pro-inflammatory molecules, advanced glycation end-products (AGEs), are elevated in PCOS and their receptor (RAGE) was upregulated in their ovaries. The AGE-RAGE axis causes production of the inflammatory cytokines IL-6 and IL-8 and worsens IR. Pigment epithelium derived factor (PEDF), is a glycoprotein known for its anti-angiogenic, anti-inflammatory and anti-oxidative properties. It has been shown to counter AGE-mediated IR in a variety of cells. We have recently characterized PEDF in the female reproductive system, and shown it to negate both angiogenic and inflammatory pathways in OHSS, which is prevalent among PCOS patients undergoing IVF treatment.

Aim: Therefore, our aim was to elucidate PEDF`s role in the metabolic aspects of PCOS.

Methods: We have established an in-vitro model of IR in human granulosa cell-line by chronic incubation with insulin/AGEs and induced IR in an in-vivo mouse PCOS model by using high fat diet (HFD).

Results: In PCOS+HFD mice, glucose response in glucose-tolerance-test was significantly different from PCOS-only mice (P<0.01). Under IR conditions, expression of IL6/8 mRNA was significantly increased (P<0.01). Under the same conditions, we further demonstrated significant elevation in PEDF both in-vitro and in-vivo (P<0.02). PEDFs receptors were significantly elevated (both mRNA (P<0.01) and protein (P<0.05)).

Conclusion: These findings suggest that PEDF is an important factor in PCOS pathogenesis- PEDF is needed to counter the harmful effects of the AGE-RAGE axis in the metabolic aspect of the syndrome.