The effects of letrozole-induced maternal hyperandrogenism on sexual behaviors, testicular histology, and serum biochemical traits in male offspring rats: An experimental study

Background: Intrauterine endocrine abnormalities have profound effects on the development of physiological disorders. Objective: This study aimed to assess the effects of in utero exposure to letrozole (an aromatase inhibitor) and its late consequences on the reproductive and metabolic performance of an adult male offspring. Materials and Methods: ۱۵ pregnant Sprague-Dawley rats (۸ wk, ۱۵۵ gr) were randomly assigned into ۵ experimental groups (n = ۳/each) and orally received either letrozole at doses of ۰.۲۵, ۰.۷۵, ۱.۰۰, and ۱.۲۵ mg/kg body weight (BW) or vehicle (control) on the gestation days of ۱۶, ۱۷, and ۱۸. Pregnancy outcome, sexual behaviors on postnatal day ۶۰, serum biochemical features, and the histopathology of testes were assessed in male offspring. Results: Compared to control group, delayed labor (۲۱.۸۳ vs. ۲۴.۲۵, p < ۰.۰۰۰۱) and reduced litter size (n = ۱۲.۲۵ vs. n = ۲, p < ۰.۰۰۰۱) were recorded in ۱.۲۵ mg/kg BW group. A reduction in high-density lipoprotein level and the elevation of testes weight, BW gain, anogenital distance, as well as the serum concentrations of testosterone, triglycerides, cholesterol, and glucose were observed in ۱.۲۵ mg/kg BW (p < ۰.۰۰۰۱) and ۱.۰۰ mg/kg BW (p < ۰.۰۰۰۱) groups in comparison to control. A larger number of anogenital female sniffing, pursuit, and mounting behaviors were also observed in ۱.۲۵ mg/kg BW group in comparison to control (p < ۰.۰۰۰۱). Severe testicular defects including necrosis and disruption of the epithelium of seminiferous tubules, sloughing of epithelial cells, and spermatogenesis arrest were observed in letrozole-treated groups, in a dose-dependent manner. Conclusion: Maternal exposure to letrozole can adversely affect the reproductive and metabolic performance of male offspring rats, suggesting an incomplete sex differentiation.

Keywords:

Androgens , Aromatase inhibitors , Rat , Sexual activities , Testes histopathology. , آندروژن ها , مهارکننده های آروماتاز , موش صحرایی , فعالیت های جنسی , هیستوپاتولوژی بیضه.