Combinatorial effect of genistein and female sex‐steroids on uterine fluid volume and secretion rate and aquaporin (AQP)−1, 2, 5, and 7 expression in the uterus in rats

We hypothesized that genistein can interfere with the regulation of uterine fluid volume, secretion rate and expression of aquaporin in the uterus by female sex‐steroids, i.e., estrogen and progesterone. Therefore, the aims of this study were to investigate changes in these parameters in the presence of genistein and female sex‐steroids. Methods: Female Sprague‐Dawley rats were ovariectomized and received 3‐days estradiol‐17β benzoate (E2) plus genistein (25, 50, or 100 mg kg^?1 day^?1) or 3‐days E2 followed by 3‐days E2 plus progesterone with genistein (25, 50, or 100 mg kg^?1 day^?1). A day after last treatment, uterine fluid secretion rate was determined by in vivo uterine perfusion with rats under anesthesia. Animals were sacrificed and uteri were harvested and subjected for histological analyses. Luminal/outer uterine circumference was determined and distribution of AQP‐1, 2, 5, and 7 in endometrium was visualized by immunofluorescence. Expression of AQP‐1, 2, 5, and 7 proteins and mRNAs were determined by Western blotting and Real‐time PCR respectively. Results: Combined treatment of E2 with high dose genistein (50 and 100 mg kg^?1 day^?1) resulted in significant decrease in uterine fluid volume, secretion rate and expression of AQP‐1, 2, 5, and 7 proteins and mRNAs in uterus (p < 0.05). No significant changes in these parameters were observed when 25 mg kg^?1 day^?1 genistein was given with E2 or when genistein was given with E2 followed by E2 plus progesterone Conclusions: Decreased in uterine fluid volume, secretion rate and AQP‐1, 2, 5, and 7 expression in the uterus by high dose genistein in the presence of E2 could potentially affect female fertility. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 832–844, 2017.