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

Abstract:

: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-γ3 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-γ3 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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Su L,Mruk DD,Lie PP,Silvestrini B,Cheng CY

doi

10.1038/ncomms2171

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

1185

issn

2041-1723

pii

ncomms2171

journal_volume

3

pub_type

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