Testosterone Reduces Tight Junction Complexity and Down-Regulates Expression of Claudin-4 and Occludin in the Endometrium in Ovariectomized, Sex-Steroid Replacement Rats

The study, conducted on 6 ovariectomized Sprague-Dawley rats per treatment group, demonstrated that testosterone reduced the complexity of tight junctions and decreased the expression of claudin-4 and occludin in the endometrium during uterine receptivity. The administration of flutamide or finasteride did not reverse these effects, indicating that testosterone's impact on tight junction morphology and protein expression is not mediated by the genomic pathway or by its active metabolite, dihydrotestosterone (DHT). These findings suggest that high levels of testosterone may disrupt uterine fluid regulation and impair embryo attachment and implantation, potentially leading to infertility. The study raises the possibility that testosterone's effects on the uterus might be through a non-genomic pathway, which had not been previously reported.