Effect of soy isoflavones on implantation losses in Wistar rat: implication of progesterone receptors, vascular endothelial growth factor and estradiol receptors alpha

Background: Implantation is a crucial period determining the success of a full pregnancy. Endocrine disruptors such as phytoestrogens (PEs) were thought to adversely influence embryonic implantations. However, the mechanism by which they upset implantation was not fully elucidated. Aims: The effect of administering soy isoflavones on the implantation of Wistar rats was studied through the detection of progesterone receptors (PR), vascular endothelial growth factor (VEGF), and estradiol receptor alpha (ER-α) protein expression at gestation day 6 (GD6). Methods: Eighteen cyclic female Wistar rats were distributed into two groups, group A: control (n=9) were fed with a casein based diet, and group B (n=9) were fed with a casein diet and gavaged 50 mg/kg/day soy isoflavones’ extract 40% starting from gestation day zero (GD0) to GD6. Feed intake, body weight (BW), body gain, and uterine weights were recorded. At the end of GD6 the number of corpora lutae (CLs) and implantation rates were recorded. Histopathology and immunohistochemistry (IHC) for PR, VEGF, and ER-α protein expression in implanted uteri were performed. Results: Soy isoflavones significantly reduced feed intake, weight gain, uterine weights CL numbers, and implantation rates of the treated pregnant dams. The endometrium of the soy treated dams showed less proliferation than that of the control. Immunostaining percentage of PR and VEGF proteins significantly reduced in soy treated dams compared to the control. However, the mean expression percentage of ER-α exhibited significant elevation in the soy treated dams in comparison to the control group. Conclusion: Implantation losses caused by soy isoflavones seemed to be due to the down regulation of PR that failed to down regulate ER-α action and decreased VEGF production.