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Mol. Hum. Reprod. Advance Access published online on January 21, 2005
Molecular Human Reproduction, doi:10.1093/molehr/gah142
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Molecular Human Reproduction © European Society of Human Reproduction and Embryology 2004; all rights reserved
Received October 27, 2004
Accepted December 15, 2004

Article

Induction of human sperm capacitation and protein tyrosine phosphorylation by endometrial cells and interleukin-6*

Julie Laflamme 1, Ali Akoum 2, and Pierre Leclerc 3*

1 Endocrinologie de la Reproduction and, Canada Centre de recherche du CHUQ, Département d'obstétrique et gynécologie, Université Laval, et Centre de recherche en Biologie de la reproduction, Canada
2 Endocrinologie de la Reproduction and, Canada
3 Endocrinologie de la Reproduction and, Canada Centre de recherche du CHUQ, Département d'obstétrique et gynécologie, Université Laval, et Centre de recherche en Biologie de la reproduction, Canada

* To whom correspondence should be addressed.
Pierre Leclerc, E-mail: pierre.leclerc{at}crsfa.ulaval.ca


  Abstract

In order to become fully competent at fertilizing the oocyte, spermatozoa must undergo the maturational process of capacitation during their journey in the female reproductive tract. Endometrial cells secrete an array of growth factors that can affect spermatozoa. Among these factors, it has been previously demonstrated that interleukin-6 (IL-6) affects the fertilizing capacity of human spermatozoa. As the expression of this cytokine varies throughout the menstrual cycle and increases during the periovulatory period, the involvement of IL-6 in human sperm capacitation was investigated, with emphasis on the signal transduction cascade triggered by this agent in sperm cells. Spermatozoa were treated with recombinant human IL-6. Protein phosphotyrosine content and localization of the phosphotyrosine containing proteins were evaluated by western blot and indirect immunofluorescence, respectively, using a monoclonal anti-phosphotyrosine antibody. The acrosomal status was evaluated on IL-6 treated spermatozoa before or after challenge with the ionophore A23187 according to the fluorescent pattern observed upon binding to the Pisum sativum agglutinin conjugated to fluorescein isothiocyanate. In the present study, it is shown that, as for endometrial cell-conditioned media, IL-6 induces human sperm capacitation. The IL-6 effects most likely occur through binding to its receptor, IL-6R{alpha}, whose presence in the sperm is also reported in this study. As for the IL-6 receptor, this is the first report on the presence of the tyrosine kinase JAK1 in the spermatozoa. Moreover, this kinase becomes phosphorylated on tyrosine residues upon sperm treatment with recombinant IL-6, which suggests its activation by the cytokine. Taken together, our results demonstrate that the IL-6 intracellular signalling machinery is present in human spermatozoa and might be involved in the acquisition of sperm fertilizing ability, also known as the capacitation process.

Keywords: capacitation; cytokines; endometrial cells; phosphotyrosine; tyrosine kinases.

*This project was supported by a grant from the Canadian Institutes of Health Research.


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