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Mol. Hum. Reprod. Advance Access published online on May 18, 2008
Molecular Human Reproduction, doi:10.1093/molehr/gan031
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

RANTES and Human Sperm Fertilizing Ability: Effect on Acrosome Reaction and Sperm/Oocyte fusion

A. Barbonetti, M.R.C. Vassallo, C. Antonangelo, V. Nuccetelli*, A. D'Angeli, F. Pelliccione, M. Giorgi*, F. Francavilla and S. Francavilla

Andrologic Unit, Department of Internal, University of L'Aquila, Italy

Address correspondence: Prof. Sandro Francavilla, M.D., Department of Internal Medicine, University of L'Aquila, Blocco 11, Coppito, 67100, Coppito, L'Aquila, Italy, Tel.: +39 0862 368338 Fax: +39 0862 368342, e-mail: sandrof{at}univaq.it

The beta-chemokine RANTES (Regulated on Activation Normal T Expressed and Secreted chemokine) is present in both the male and female genital tract fluids where its levels increase in diseases related to infertility, such as endometriosis and male genital tract infections. Beta-chemokine receptors (CCR3 and CCR5) are expressed on freshly ejaculated human sperm cells and a sperm chemoactractant effect for RANTES has been reported. No information exists on other possible roles of RANTES on sperm functions involved in the fertilization process. In the present study, the exposure of sperm suspensions to high concentrations of the chemokine, comparable to those observed in inflammatory diseases, significantly decreased the stimulatory effect exerted by progesterone (P) on sperm/oocyte fusion, evaluated by means of the hamster egg penetration test (HEPT). Accordingly, a large proportion of spermatozoa preincubated under capacitating conditions with high concentrations of RANTES underwent a premature acrosome reaction (AR) that prevented subsequent P-induced AR. Finally, sperm samples exposed to the same high levels of chemokine showed a significant increase in the intracellular levels of cAMP, which is involved in capacitation and AR dynamics. These results indicate a negative interference of high levels of RANTES on the sperm fertilizing ability, thereby suggesting a potential contribution of this chemokine to subfertility associated with endometriosis and genital tract inflammatory diseases.

Key Words: RANTES/Fertilization/Human Spermatozoa/Acrosome Reaction/sperm/oocyte fusion

* Department of Basic and Applied Biology, University of L'Aquila, Italy

Submitted on February 13, 2008; resubmitted on May 9, 2008; accepted on May 13, 2008.


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