Pigment-Epithelium derived Factor (PEDF) is a signaling molecule in the human ovary and possibly involved in PCOS

Background/Objectives: Recent proteomic studies indicated that Pigment Epithelium Derived Factor (PEDF) is a component of human ovarian follicular fluid (FF). This multifunctional factor can induce apoptosis in endothelial cells, exert anti-apoptotic and neurotrophic actions in neurons and may have anti-angiogenetic and antioxidant properties. Therefore we determined PEDF levels in FF, identified the producing cells and explored possible functions in human ovary, IVF-derived FF and cultured human granulosa cells (GCs).

Methods/Results: PEDF was detected in high concentrations in FFs of 10 IVF patients (ELISA measurements). Both FF and GCs of large antral follicles in human ovarian sections were immunoreactive for PEDF, implying that this factor is produced and secreted by GCs. This was verified in cultured human GCs by RT-PCR/sequencing. Because GCs express a known PEDF receptor, they may be targets for this factor. In order to explore this possibility, we performed ROS measurements with the fluorescent dye H₂DCFDA. Addition of exogenous recombinant human PEDF within minutes resulted in a concentration-dependent generation of ROS, which was blocked by the antioxidant N-acetyl-cysteine (NAC). High ROS levels are thought to be involved in polycystic ovarian syndrome (PCOS). When we studied cultured GCs from women suffering from PCOS, we found a significant increase in PEDF mRNA levels, implying that they produce more of this factor. Furthermore, preliminary ELISA measurements of FF suggest that PEDF levels in FF of PCOS patients are significantly increased.

Summary/Conclusion: PEDF is secreted by human GCs in vivo and in vitro. It is present in FF and causes the generation of ROS in cultured GCs. Furthermore, GCs from PCOS produce more PEDF. Hence, via ROS it may play important roles in ovarian follicular physiology and pathology.

(Supported by Friedrich Baur-Stiftung and DFG MA1080/17 – 3)