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Hum. Reprod. Advance Access published online on August 11, 2005
Human Reproduction, doi:10.1093/humrep/dei241
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
Received February 2, 2005
Revised May 18, 2005
Accepted July 1, 2005

Article

Cyclic FEE peptide increases human gamete fusion and potentiates its RGD-induced inhibition

A. Ziyyat 1, N. Naud-Barriant 1, V. Barraud-Lange 1, F. Chevalier 1, O. Kulski 1, T. Lemkecher 1, M. Bomsel 2, and J.P. Wolf 1*

1 Laboratoire de Biologie de la Reproduction, UPRES 3410, UFR SMBH, Université Paris 13, 74, rue Marcel Cachin, 93017 Bobigny, Service d’Histologie-Embryologie-Cytogénétique, Hôpital Jean Verdier (Assistance Publique-Hôpitaux de Paris), Bondy
2 Laboratoire ‘Entrée muqueuse du VIH et immunité muqueuse’, Unité INSERM U567, Institut Cochin, 22, rue Méchain, 75014 Paris, France

* To whom correspondence should be addressed.
J.P. Wolf, E-mail: jean-philippe.wolf{at}jvr.ap-hop-paris.fr


  Abstract

BACKGROUND: {alpha}6{beta}1 integrin has been proposed to act as a sperm receptor on the mouse oocyte by interacting with spermatozoon fertilin {beta}. We investigated, in humans, whether oocyte integrins could act similarly in gamete fusion, using a cyclic peptide containing the putative disintegrin-binding domain of human fertilin {beta} [cyclic FEE (cFEE)] and RGD peptide. METHODS: Zona-free eggs were inseminated in the absence or presence of peptides. To maintain the membrane protein pattern, the zona pellucida was removed by microdissection. Immunofluorescence and confocal microscopy were used to detect integrin subunits on the oocyte. RESULTS: Unexpectedly, cFEE alone increased human gamete fusion by 94% instead of inhibiting fertilization. Furthermore, cFEE together with RGD potentiated the RGD-induced inhibition of fertilization in a dose-dependent manner. The data suggested the hypothesis of integrin cross-talk, further supported by the co-localization of {alpha}6{beta}1 and {alpha}v{beta}3 integrins, the putative receptors of cFEE and RGD peptides, respectively. CONCLUSIONS: RGD-sensitive and -insensitive integrins may be associated in a multimolecular complex working as a sperm receptor on the human oocyte membrane. Supplementation of human IVF culture medium with cFEE peptide might improve fertilization rates in ART.

Keywords: FEE/fertilization/human/integrins/RGD.
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