Androgen regulation, biological activity and cell signaling of beta-defensins in the epididymis morphogenesis

Abstract

Reproductive disorders related to male reproductive tract are of public health interest. Many reproductive problems in adult men have unknown etiology and part of them is due to the influence of environmental factors affecting the morphogenesis and the masculinization of the male reproductive tract. In adults, the epididymis is an essential organ for sperm maturation and production of viable spermatozoa, which are required for fertilization. The mesonephric duct (also known as Wolffian duct), the anlagen of the epididymis, goes through a process of tubuloepithelial morphogenesis induced by androgens that originates the epididymis. Disruption of the morphological differentiation of this structure may result in infertility at adulthood. Therefore, there is a need for a better understanding of the mechanisms and mediators of the androgen action that govern epididymis development. In the last years our research group has identified the beta-defensin SPAG11C (sperm associated antigen 11 C) as an androgen-dependent mesenchymal factor that has a role in modulating the mesonephric duct morphogenesis in rats. Here we present the basis of this discovery and the experimental data that expanded our view of beta-defensins in this embryonic tissue and gave support to our aim to investigate the androgen regulation and the functional aspects of beta-defensins during the rat epididymis morphogenesis, focusing on beta-defensins DEFB1 (defensin beta 1) and DEFB2. For this purpose, we will evaluate: a) the androgenic modulation of beta-defensins DEFB1 and DEFB2 in ex vivo cultured mesonephric duct; b) the androgenic modulation of these two beta-defensins in mesonephric duct from androgen receptor knockout mice (ARKO); c) the effects of beta-defensins DEFB1 and DEFB2 (recombinant proteins) on the morphogenesis of the ex vivo cultured mesonephric duct and d) the cellular and molecular basis of the effects of beta-defensins in ex vivo cultured mesonephric duct. (AU)