CD43 expressed in Sertoli, Leydig and germ cells inhibits testicular function and represents a potential target to treat male infertility or effect male contraception

CD43 is a heavily glycosylated transmembrane molecule that plays critical roles in leukocyte activation and adhesion. Previously, only hematopoietic cells were thought to normally express CD43. However, our immunohistochemical analysis of normal human testes demonstrates that the N-terminal domain of CD43 is expressed in the cytoplasm of Sertoli and Leydig cells while the C-terminal domain is expressed separately in the nucleus of Sertoli and germ cells. The observation that normal testicular cells express CD43 is entirely novel and indicates that testes function is controlled in ways not previously imagined. In order to begin to identify these CD43-dependent functions, CD43 expression was knocked down in the human germ cell line TCam-2. This knockdown changed the expression of both Transition Protein 1 and Acrosin consistent with spermatid maturation having been driven forward. In addition, down-regulation of CD43 in the mouse Leydig cell line MLTC-1 significantly induced its secretion of estradiol, testosterone and progesterone. Based on these data we propose that CD43 actively inhibits testicular function and its aberrant over-expression may contribute to male infertility. Therapeutics that induce such over-expression may represent a means of effecting male contraception.