Signaling pathways involved in human sperm hyperactivated motility stimulated by Zn 2+

Deborah Allouche-Fitoussi, Danit Bakhshi, Haim Breitbart

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17 Scopus citations


To fertilize the egg, sperm cells must reside in the female reproductive tract for several hours during which they undergo chemical and motility changes collectively called capacitation. During capacitation, the sperm develop a unique type of motility known as hyperactivated motility (HAM). The semen contains Zn 2+ in millimolar concentrations, whereas in the female reproductive tract, the concentration is around 1 µM. In this study, we characterize the role of Zn 2+ in human sperm capacitation focusing on its effect on HAM. Western blot analysis revealed the presence of GPR39-type Zn-receptor localized mainly in the sperm tail. Zn 2+ at micromolar concentration stimulates HAM, which is mediated by a cascade involving GPR39–adenylyl cyclase (AC)–cyclic AMP (cAMP)–protein kinase A–tyrosine kinase Src (Src)–epidermal growth factor receptor and phospholipase C. Both the transmembrane AC and the soluble-AC are involved in the stimulation of HAM by Zn 2+ . The development of HAM is precisely regulated by cAMP, in which relatively low concentration (5–10 µM) stimulated HAM, whereas at 30 µM no stimulation occurred. A similar response was seen when different concentrations of Zn 2+ were added to the cells; low Zn 2+ stimulated HAM, whereas at relatively high Zn 2+ , no effect was seen. We further demonstrate that the Ca 2+ -channel CatSper involved in Zn 2+ -stimulated HAM. These data support a role for extracellular Zn 2+ acting via GPR39 to regulate signaling pathways in sperm capacitation, leading to HAM induction.

Original languageEnglish
Pages (from-to)543-556
Number of pages14
JournalMolecular Reproduction and Development
Issue number6
StatePublished - Jun 2018

Bibliographical note

Publisher Copyright:
© 2018 Wiley Periodicals, Inc.


This work was supported by IHEL Foundation to H. Breitbart.

FundersFunder number
Ihel Foundation


    • capacitation
    • hyperactivation
    • motility
    • signaling
    • spermatozoa
    • zinc


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