A peptide derived from laminin-γ3 reversibly impairs spermatogenesis in rats

Cellular events that occur across the seminiferous epithelium of the mammalian testis during spermatogenesis are tightly coordinated by biologically active peptides released from laminin chains. Laminin-γ3 domain IV (Lam γ3 DIV) is released at the apical ectoplasmic specialization (ES) during spermiation and mediates restructuring of the blood-testis barrier (BTB), which facilitates the transit of preleptotene spermatocytes. Here we determine the biologically active domain in Lam γ3 DIV, which we designate F5-peptide, and show that overexpression of this domain, or the use of a synthetic F5-peptide, in Sertoli cells with an established functional BTB reversibly perturbs BTB integrity in vitro and in rat testis in vivo. This effect is mediated via changes in protein distribution at the Sertoli and Sertoli-germ cell-cell interface and by phosphorylation of focal adhesion kinase at Tyr(407). The consequences are perturbed organization of actin filaments in Sertoli cells, disruption of the BTB and spermatid loss. The impairment of spermatogenesis suggests that this laminin peptide fragment may serve as a contraceptive in male rats.