Maurya Vineet Kumar, Sangappa Chadchan, Kumar Vijay, Mahfooz Sahil, Singh Archana, Rajender Singh, Jha Rajesh Kumar
Division of Endocrinology, Life Science North 111B/101, CSIR-Central Drug Research Institute, B,S, 10/1, Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
J Ovarian Res. 2014 Mar 14;7:32. doi: 10.1186/1757-2215-7-32.
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.
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 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.
The 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.
We 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.
多囊卵巢综合征（PCOS）的特征是存在多个卵泡囊肿，由于无排卵而导致不孕。该综合征在全球约10%的女性中出现。导致PCOS的确切分子机制仍不清楚。RhoGTPase与卵子发生有关，但其在PCOS中的作用仍未被探索。因此，我们试图阐明PCOS小鼠模型中的Vav-Rac1信号通路。
通过注射脱氢表雄酮（DHEA）20天建立PCOS小鼠模型。采用免疫印迹和光密度测定法分析Rac1、pRac1、Vav、pVav和小窝蛋白1的表达水平。通过免疫沉淀研究Vav与Rac1蛋白之间的关联。此外，我们使用生化分析方法分析卵巢中Rac1的活性以及抑制素B和17β-雌二醇的水平。
组织学证实卵巢中存在多个卵泡囊肿。PCOS卵巢中Rac1（GTP结合状态）的活性显著降低。同样，与假手术组卵巢相比，PCOS中Rac1及其磷酸化形式（pRac1）的表达水平降低。Rac1的鸟嘌呤核苷酸交换因子Vav的表达水平和活性（磷酸化形式）中度下调。我们观察到多囊卵巢中小窝蛋白1、17β-雌二醇和抑制素B的表达相对增加。
我们得出结论，DHEA诱导的高雄激素血症（PCOS）会降低卵巢中Rac1和Vav的表达及活性，同时小窝蛋白1的表达增加。这伴随着卵巢内17β-雌二醇和抑制素B水平的升高。
