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First published online 8 October 2008
doi: 10.1242/dev.024521

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Mobilisation of Ca²⁺ stores and flagellar regulation in human sperm by S-nitrosylation: a role for NO synthesised in the female reproductive tract

¹ School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.
² Centre for Human Reproductive Science, Birmingham Women's Hospital, Birmingham B15 2TG, UK.
³ Reproductive Biology and Genetics Research Group, The Medical School, University of Birmingham, Birmingham B15 2TT, UK.
⁴ Center for Research in Contraceptive and Reproductive Health, Department of Cell Biology, PO Box 800732, University of Virginia, Charlottesville, VA 22908, USA.
⁵ Division of Maternal and Child Health Sciences, Medical School, University of Dundee, Ninewells Hospital, Dundee DD1 9SY, UK.

^* Author for correspondence (e-mail: s.j.publicover{at}bham.ac.uk)

Accepted 22 September 2008

Generation of NO by nitric oxide synthase (NOS) is implicated in gamete interaction and fertilisation. Exposure of human spermatozoa to NO donors caused mobilisation of stored Ca²⁺ by a mechanism that did not require activation of guanylate cyclase but was mimicked by S-nitroso-glutathione (GSNO; an S-nitrosylating agent). Application of dithiothreitol, to reduce protein -SNO groups, rapidly reversed the actions of NO and GSNO on [Ca²⁺]_i. The effects of NO, GSNO and dithiothreitol on sperm protein S-nitrosylation, assessed using the biotin switch method, closely paralleled their actions on [Ca²⁺]_i. Immunofluorescent staining revealed constitutive and inducible NOS in human oviduct and cumulus (the cellular layer investing the oocyte). 4,5-diaminofluorescein (DAF) staining demonstrated production of NO by these tissues. Incubation of human sperm with oviduct explants induced sperm protein S-nitrosylation resembling that induced by NO donors and GSNO. Progesterone (a product of cumulus cells) also mobilises stored Ca²⁺ in human sperm. Pre-treatment of sperm with NO greatly enhanced the effect of progesterone on [Ca²⁺]_i, resulting in a prolonged increase in flagellar excursion. We conclude that NO regulates mobilisation of stored Ca²⁺ in human sperm by protein S-nitrosylation, that this action is synergistic with that of progesterone and that this synergism is potentially highly significant in gamete interactions leading to fertilisation.

Key words: Calcium, Cumulus, Motility, Nitric oxide, Oviduct, Sperm, Human

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This article has been cited by other articles:

				G. Machado-Oliveira, L. Lefievre, C. Ford, M. B. Herrero, C. Barratt, T. J. Connolly, K. Nash, A. Morales-Garcia, J. Kirkman-Brown, and S. Publicover Mobilisation of Ca2+ stores and flagellar regulation in human sperm by S-nitrosylation: a role for NO synthesised in the female reproductive tract J. Cell Sci., November 15, 2008; 121(22): e1 - e1. [Full Text]