Abstract:
Background
Polycystic ovarian syndrome (PCOS) is characterized by the presence of multiple follicular cysts, giving rise to infertility due to anovulation. This syndrome affects about 10% of women, worldwide. The exact molecular mechanism leading to PCOS remains obscure. RhoGTPase has been associated with oogenesis, but its role in PCOS remains unexplored. Therefore, we attempted to elucidate the Vav-Rac1 signaling in PCOS mice model.
Methods
We generated a PCOS mice model by injecting dehydroepiandrosterone (DHEA) for a period of 20 days. The expression levels of Rac1, pRac1, Vav, pVav and Caveolin1 were analyzed by employing immuno-blotting and densitometry. The association between Vav and Rac1 proteins was studied by immuno-precipitation. Furthermore, we analyzed the activity of Rac1 and levels of inhibin B and 17β-estradiol in ovary using biochemical assays.
Results
The presence of multiple follicular cyst in ovary were confirmed by histology. The activity of Rac1 (GTP bound state) was significantly reduced in the PCOS ovary. Similarly, the expression level of Rac1 and its phosphorylated form (pRac1) was decreased in PCOS in comparison to the sham treated ovary. The expression level and activity (phosphorylated form) of activator or guanine nucleotide exchanger of Rac1, Vav was moderately down-regulated. We observed comparatively increased expression of Caveolin1, 17β-estradiol, and inhibin B in the polycystic ovary.
Conclusion
We conclude that hyperandrogenization (PCOS) by DHEA diminishes ovarian Rac1 and Vav expression and activity along with an increase in expression of Caveolin1. Further, the levels of intra-ovarian 17β-estradiol and inhibin B were also found to be elevated in the polycystic ovary.
