4.5 Review

Sperm ion channels and transporters in male fertility and infertility

Journal

NATURE REVIEWS UROLOGY
Volume 18, Issue 1, Pages 46-66

Publisher

NATURE RESEARCH
DOI: 10.1038/s41585-020-00390-9

Keywords

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Funding

  1. Yale University School of Medicine
  2. Grantham Foundation
  3. NIH [R01 HD 096745]

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Mammalian sperm cells must adapt to various cues and dynamically regulate ion signaling to complete the fertilization process. Ion channels and membrane receptors play a crucial role in sperm activity, making them attractive targets for therapeutics and potentially impacting assisted reproductive technologies.
Mammalian sperm cells must respond to cues originating from along the female reproductive tract and from the layers of the egg in order to complete their fertilization journey. Dynamic regulation of ion signalling is, therefore, essential for sperm cells to adapt to their constantly changing environment. Over the past 15 years, direct electrophysiological recordings together with genetically modified mouse models and human genetics have confirmed the importance of ion channels, including the principal Ca2+-selective plasma membrane ion channel CatSper, for sperm activity. Sperm ion channels and membrane receptors are attractive targets for both the development of contraceptives and infertility treatment drugs. Furthermore, in this era of assisted reproductive technologies, understanding the signalling processes implicated in defective sperm function, particularly those arising from genetic abnormalities, is of the utmost importance not only for the development of infertility treatments but also to assess the overall health of a patient and his children. Future studies to improve reproductive health care and overall health care as a function of the ability to reproduce should include identification and analyses of gene variants that underlie human infertility and research into fertility-related molecules. Mammalian sperm must respond to a variety of cues, and dynamic regulation of ion signalling is, therefore, essential for sperm cells to adapt to their environment. In this Review, the authors describe the ion channels and membrane receptors controlling sperm activity, in particular the principal Ca2+-selective plasma membrane ion channel CatSper, and consider how sperm ion channels and membrane receptors are attractive targets for therapeutics and how these signalling processes might have implications for assisted reproductive technologies.

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