Altered expression and localization of estrogen receptors alpha and beta in the testes of a cryptorchid rat model

Objectives: To assess the involvement of estrogen in spermatogenesis, we evaluated the expression of estrogen receptors (ERs) alpha (ERalpha) and beta (ERbeta) in the cryptorchid testes in model rats exposed to flutamide during the fetal stage.

Methods: Cryptorchid model rats were produced by administering flutamide to pregnant Sprague-Dawley rats. To evaluate the sequential change in the expression of ERalpha and ERbeta genes, real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was performed using specific primers. Immunohistochemistry with ERalpha and ERbeta antibodies was performed, and the results were evaluated to determine the influences of orchiopexy.

Results: Real-time RT-PCR revealed that ERalpha expression in control testes increases with growth and peaks value at 7 weeks and significantly decreases in cryptorchid testes. ERbeta expression was low, and there were no significant differences between both the cryptorchid and control testes groups. Immunohistochemistry revealed that ERalpha protein was present in the spermatids and Sertoli cells of descended testes, and that this protein was strongly expressed in the Leydig cells of cryptorchid testes. ERbeta was detected in multiple cells in both groups. After orchiopexy, ERalpha expression was detected in the spermatids of cryptorchid testes.

Conclusions: Spermatogenesis in cryptorchid rats is disrupted. Because the expression of ERbeta was unchanged in both control and cryptorchid testes, we supposed that alteration in ERalpha levels is more closely related to spermatogenic failure than ERbeta levels in the cryptorchid testes. We considered that increased expression of ERalpha in Leydig cells of cryptorchid testes is associated with estradiol level in the testicular tissue, and androgen-estrogen imbalance deteriorates spermatogenesis in cryptorchidism.