Pigment epithelium derived factor PEDF exerts antioxidative effects in granulosa cells

Recombinant pigment epithelium–derived factor can protect granulosa cell viability in oxidative stress conditions by increasing SOD-1 and GPX- 2 mRNA levels, decreasing the protein level of BAX, and inducing AKT phosphorylation.

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Authors

Hadas Bar-Joseph, Ph.D., Ido Ben-Ami, M.D., Ph.D., Raphael Ron-El, M.D., Ruth Shalgi, Ph.D., Dana Chuderland, Ph.D.

Volume 102, Issue 3, Pages 891-898

Abstract

Objective:

To determine whether supplementing granulosa cells cultures with pigment epithelium–derived factor (PEDF) can protect them from oxidative stress.

Design:

We used either granulosa cell line or human primary granulosa cell culture from women undergoing in vitro fertilization (IVF) treatments.

Setting:

University research facilities.

Animal(s):

Imprinting control region female mice.

Intervention(s):

Recombinant PEDF (rPEDF) was added to cultures of either primary granulosa cell culture or granulosa cell line in the present or absence of H2O2 triggering.

Main Outcome Measure(s):

We followed cell viability with the use of methylthiazolyl tetrazolium assay and tracked PEDF mechanism of action with the use of Western blot analysis, measuring the level of SOD-1 and GPX-1 mRNA, protein level of BAX, and phosphorylation of AKT.

Result(s):

We found that granulosa cell viability and the level of PEDF mRNA were both significantly reduced, in a dose-dependent manner, after exposure to H2O2. The rate of H2O2-induced apoptosis was significantly attenuated in granulosa cells treated with rPEDF. We showed that granulosa cells, of both humans and rodents, express the PEDF receptor, PNPLA2; once stimulated by rPEDF, the cells exhibited phosphorylation of AKT. Finally, we showed that PEDF exerts its antioxidative activity through the AKT signaling pathway.

Read the full text at: http://www.fertstert.org/article/S0015-0282(14)00545-7/fulltext


Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.