A peptide derived from laminin-gamma 3 reversibly impairs spermatogenesis in rats

作者：Su Linlin; Mruk Dolores D; Lie Pearl P Y; Silvestrini Bruno; Cheng C Yan^*

来源：Nature Communications, 2012, 3: 1185.

DOI：10.1038/ncomms2171

Cellular events that occur across the seminiferous epithelium in the mammalian testis during spermatogenesis are tightly coordinated by biologically active peptides released from laminin chains. Laminin-gamma 3 domain IV is released at the apical ectoplasmic specialization during spermiation and mediates restructuring of the blood-testis barrier, which facilitates the transit of preleptotene spermatocytes. Here we determine the biologically active domain in laminin-gamma 3 domain IV, which we designate F5 peptide, and show that the overexpression of this domain, or the use of a synthetic F5 peptide, in Sertoli cells with an established functional blood-testis barrier reversibly perturbs blood-testis barrier integrity in vitro and in the 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 blood-testis barrier and spermatid loss. The impairment of spermatogenesis suggests that this laminin peptide fragment may serve as a contraceptive in male rats.

• 出版日期2012-11