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Calcium signalling during human sperm interaction with cells of the female reproductive tract

Connolly, Thomas James (2012)
Ph.D. thesis, University of Birmingham.

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Abstract

The female reproductive tract acts not only as a complex mediator of sperm function and selection but animal data suggests that it alters protein expression after exposure to sperm, implying two-way communication. We have used single-cell fluorescence imaging to observe [Ca2+]i signalling in human female reproductive tract cells upon initial contact with sperm and in sperm during binding and release events. Parallel experiments were also performed on a model human oviductal cell line, OE E6/E7 and a control, human foreskin fibroblasts. Upon exposure to sperm, tract cells generated [Ca2+]i signals through mobilisation of thapsigargin-sensitive intracellular Ca2+ stores. The percentage of significant [Ca2+]i responses varied in different anatomical regions of the female tract. Furthermore, [Ca2+]i signalling was observed upon exposure to sperm-conditioned media suggesting signalling factors may be shed or secreted by sperm. Human foreskin fibroblasts were unresponsive to sperm.

Co-culture of sperm with tract explants induced post-translational modification of sperm proteins through NO-dependant S-nitrosylation. We have also provided initial evidence for [Ca2+]i alterations in sperm during binding to and detachment from oviductal explants.

We conclude that sperm can elicit [Ca2+]i signals in female tract cells upon initial contact though mobilisation of intracellular Ca2+ stores. This may reflect events upstream of reported gene and protein expression changes. In addition, human sperm interaction with oviductal epithelium is likely to be important in modulating sperm function during migration and associated events through the female reproductive tract.

Type of Work:Ph.D. thesis.
Supervisor(s):Kirkman-Brown, Jackson
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Clinical and Experimental Medicine
Subjects:RG Gynecology and obstetrics
Institution:University of Birmingham
ID Code:3411
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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