title: 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.
authors.affiliation: The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, 1230 York Avenue, New York, New York 10065, USA.
authors.forename: Linlin
authors.initials: L
authors.lastname: Su
authors.forename: Dolores D
authors.initials: DD
authors.lastname: Mruk
authors.forename: Pearl P Y
authors.initials: PP
authors.lastname: Lie
authors.forename: Bruno
authors.initials: B
authors.lastname: Silvestrini
authors.forename: C Yan
authors.initials: CY
authors.lastname: Cheng
mesh_terms: D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001814:Blood-Testis Barrier / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D007797:Laminin / Q000737:chemistry*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D062793:Occludin / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013091:Spermatogenesis / Q000187:drug effects*; D013094:Spermatozoa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism
chemical_list: D000199:Actins; D007797:Laminin; D062793:Occludin; D010446:Peptide Fragments; D010455:Peptides; D051416:Focal Adhesion Protein-Tyrosine Kinases