A peptide derived from laminin-γ3 reversibly impairs spermatogenesis in rats
Linlin Su,
Dolores D. Mruk,
Pearl P.Y. Lie,
Bruno Silvestrini and
C. Yan Cheng ()
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Linlin Su: The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, 1230 York Avenue, New York, New York 10065, USA
Dolores D. Mruk: The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, 1230 York Avenue, New York, New York 10065, USA
Pearl P.Y. Lie: The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, 1230 York Avenue, New York, New York 10065, USA
Bruno Silvestrini: Faculty of Pharmacy, University of Rome La Sapienza, P. le Aldo Moro 5, 00185, Rome, Italy
C. Yan Cheng: The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, 1230 York Avenue, New York, New York 10065, USA
Nature Communications, 2012, vol. 3, issue 1, 1-13
Abstract:
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 Tyr407. 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.
Date: 2012
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms2171
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DOI: 10.1038/ncomms2171
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