Abstract
BackgroundPolycystic 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.MethodsWe 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 were studied by immuno-precipitation. Furthermore, we analyzed the activity of Rac1 and levels of inhibin B and 17β-estradiol in ovary using biochemical assays.ResultsThe presence of multiple follicular cysts in ovary were confirmed by histology. The activity of Rac1 (GTP bound state) was significantly reduced in the PCOS ovary. Similarly, the expression levels of Rac1 and its phosphorylated form (pRac1) were decreased in PCOS in comparison to the sham ovary. The expression level and activity (phosphorylated form) of guanine nucleotide exchanger of Rac1, Vav, was moderately down-regulated. We observed comparatively increased expressions of Caveolin1, 17β-estradiol, and inhibin B in the polycystic ovary.ConclusionWe conclude that hyperandrogenization (PCOS) by DHEA diminishes ovarian Rac1 and Vav expression and activity along with an increase in expression of Caveolin1. This is accompanied by an increase in the intra-ovarian level of '17 β-estradiol and inhibin B.
Highlights
The pool of primordial follicles in the ovary supply eggs for the entire reproductive life in mammals
Characterization of Polycystic ovarian syndrome (PCOS) by histological analysis To demonstrate the effect of DHEA, ovaries were sectioned and stained with hematoxylin/eosin
To evaluate whether DHEA can modulate of intra-ovarian activity of Rac1, we further evaluated the activity and expression level of Vav in the ovary after DHEA treatment
Summary
The pool of primordial follicles in the ovary supply eggs for the entire reproductive life in mammals. Polycystic ovarian syndrome (PCOS) is characterized by anovulation and in the presence of multiple small cysts typically arranged in the periphery of one or both ovaries. PCOS can affect 5–10% of women during their reproductive age and contributes to this etiology in about 10% of the infertile women [4,5,6] This disorder is considered to be a manifestation of the disturbance in the endocrine system, which causes secondary disorders contributing to female infertility [7]. 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. We attempted to elucidate the Vav-Rac signaling in PCOS mice model
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