Beta-defensins: new mediators of androgen action during epididymal morphogenesis?

Abstract

The Wolffian duct is the embryonic precursor of the epididymis, which is an organ of great importance for male fertility. In utero morphological differentiation of this duct depends on androgen action and abnormalities during this period can result in infertility on adulthood. Androgens are the primary factors regulating epididymal function, but the mechanisms underlying androgen action in the Wolffian duct have not been fully clarified yet. On the adult animal, some antimicrobial proteins, particularly members of beta-defensin family, show abundant expression in the epididymis and many of them are regulated by androgens. Beta-defensins have been shown as multifunctional proteins, and may participate in sperm function. However, their biological roles in male reproductive system development have been poorly explored. Our group has shown that one particular beta-defensin, SPAG11C (sperm associated antigen 11 isoform C), is expressed on the rat Wolffian duct. Additionally, several beta-defensins are differentially expressed during epididymal morphogenesis. On the basis of our most recent data, we have been suggesting that beta-defensins act as mediators of androgen action in the epididymal development by distinct biological roles. To validate our hypothesis, we propose to characterize the spatial-temporal expression profile and the androgen regulation of a subset of beta-defensins [Defb1 (defensin beta 1), Defb2 and Spag11e] during the embryonic stage of rat epididymal development. The insights generated in this study can contribute to better understanding of the epididymal morphogenesis and events related to male fertility.