PEDF Involvement in Folliculogenesis
2Department of Obstetrics and Gynecology, Shaare Zedek Medical Center, IVF and Infertility Unit, Israel
3TMCR Unit, Sackler Faculty of Medicine, Tel Aviv University, Israel
Introduction:
Follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH) are central factors in ovarian folliculogenesis. Pigment epithelium-derived factor (PEDF) is a multipotential secreted protein, known for its anti-angiogenic, anti-inflammatory, and anti-oxidative properties. PEDF is abundantly present in the female reproductive tract, hormonally regulated in the ovary and expressed conversely to VEGF. The role of FSH and AMH during folliculogenesis is well established; however, information regarding PEDF expression does not exist and its cross talk with other factors remains unknown.
Aim:
Study the role of PEDF in ovarian folliculogenesis and the crosstalk among FSH, AMH and PEDF.
Materials & Methods:
Mice: ovarian follicles at various developmental stages (small secondary, pre-antral and antral follicles) were analyzed individually using “Cells-to-CT” kit. Human: human primary granulosa cells (hpGCs) of IVF patients were collected, washed, cultured, and stimulated with recombinant (r) PEDF, FSH or AMH, to follow the crosstalk among them. qPCR was used to analyze mRNA expression of PEDF, AMH, VEGF and FSHR genes in follicles and hpGCs.
Results:
All throughout mice folliculogenesis, dynamic changes in AMH, FSHR and PEDF mRNA levels and in PEDF/VEGF ratio were observed. Positive correlation between PEDF and AMH mRNA levels was found. Stimulation of hpGCs with rPEDF (5nM/ml) significantly increased the level of AMH mRNA; whereas stimulation by rFSH (50ng/ml) or rAMH (60ng/ml) decreased the expression of PEDF mRNA significantly.
Conclusions:
PEDF expression changes during folliculogenesis. There is clear evidence for a direct interaction between PEDF and AMH.