Low-dose arsenic exposure disrupts rat uterine physiology independent of generation of oxidative stress.

Arsenic is known to adversely affect the female reproductive physiology, specifically at environmentally-relevant or accidentally-high doses, mostly by generation of high amounts of reactive oxygen species (ROS). However, the exact molecular events at very low doses of arsenic exposure, leading to uterine dysfunctions haven't yet been ascertained. This study aims to evaluate the effect and mechanism of action of oral exposure to 0.4 ppm arsenic for 28 days in adult female albino rats. Alterations in the uterine histomorphology, levels of serum estradiol, expression of the estrogen receptor and cell cycle regulating genes were analyzed. The levels of glutathione, catalase and SOD were also evaluated biochemically. The results indicated that rats exposed to 0.4 ppm sodium arsenate showed reduced circulating levels of estradiol, along with degeneration of epithelial cells of uterine lumen and endometrial glands. Concomitantly, downregulation of the estrogen receptor alpha (ERα), cell cycle regulating proteins (cyclin D1, CDK4), PI3K and Akt were also observed. However, no significant change was observed in the levels of the cellular antioxidant components. The findings thereby indicate that arsenic, at very low concentrations, leads to debilitating effects in the rat physiology by modulating estradiol production, estrogen receptor expression and uterine cell proliferation, without involving redox imbalance, eventually leading to reproductive failures.