PEDF As a Possible Marker for Early Onset of Reproductive Aging

Introduction:
Aging has a detrimental effect on the female reproductive system, manifested by deteriorated fertility parameters as hampered oocyte quality and poor embryo development. Our previous work established the anti-oxidative potential of a multipotential protein, Pigment epithelium-derived factor (PEDF) in alleviating oxidative damage in granulosa cells (GCs) of both women and mice, and oocytes in mouse model.

Aim:
To elucidate the involvement of PEDF in ovarian aging.

Methods:
Using young and reproductively aged (“aged”) mice, (n≥19), we analyzed: (1) Relative mRNA expression of PEDF, VEGF, AMH and FSHR in GCs; (2) in vitro matured oocytes’ (IVM) rate; (3) oocytes’ ATP content± rPEDF (5nM). Furthermore, we collected GCs and follicular fluids (FF) from young and aged patients undergoing IVF, (n≥10) and performed similar qPCR analysis, and determined by ELIZA PEDF protein level in GCs and FF.

Results:
rPEDF significantly improved oocytes’ IVM rate of aged compared to young mice whereas the level of ATP and mtDNA remained similar. The level of PEDF mRNA was significantly higher in GCs of aged mice and women, compared to that of young controls, with no significant changes in the expression level of VEGF, AMH or FSHR mRNA. However, in aged women, the level of PEDF protein in both GCs and in FF, was significantly lower, with no change in PEDF secretion ratio pointing on translational problem.

Conclusions:
Our findings demonstrate the involvement of PEDF in early stages of ovarian aging leading us to suggest PEDF as a possible marker for early onset of reproductive aging.