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ERK1/2 mediates sperm acrosome reaction through elevation of intracellular calcium concentration

Published online by Cambridge University Press:  15 July 2014

Yael Jaldety  and
Haim Breitbart
Yael Jaldety
Affiliation:
The Mina & Everard Faculty of Life-Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Haim Breitbart*
Affiliation:
The Mina & Everard Faculty of Life-Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
*
All correspondence to: Professor Haim Breitbart. The Mina & Everard Faculty of Life-Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel. e-mail: haim.breitbart@biu.ac.il
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Summary

Mammalian sperm acquire fertilization capacity after residing in the female reproductive tract for a few hours in a process called capacitation. Only capacitated sperm can bind the zona pellucida (ZP) of the egg and undergo the acrosome reaction, a process that allows penetration and fertilization. Extracellular signal regulated kinase (ERK1/2) mediates signalling in many cell types, however its role in sperm function is largely unknown. Here we show that ERK1/2 is highly phosphorylated/activated after a short incubation of mouse sperm under capacitation conditions and that this phosphorylation is reduced after longer incubation. Further phosphorylation was observed upon addition of crude extract of egg ZP or epidermal growth factor (EGF). The mitogen-activated ERK-kinase (MEK) inhibitor U0126 abolished ERK1/2 phosphorylation, in vitro fertilization rate and the acrosome reaction induced by ZP or EGF but not by the Ca2+-ionophore A23187. Moreover, inhibition of ERK1/2 along the capacitation process diminished almost completely the sperm's ability to go through the acrosome reaction, while inhibition at the end of capacitation attenuated the acrosome reaction rate by only 45%. The fact that the acrosome reaction, induced by the Ca2+ -ionophore A23187, was not inhibited by U0126 suggests that ERK1/2 mediates the acrosome reaction by activating Ca2+ transport into the cell. Direct determination of intracellular [Ca2+] revealed that Ca2+ influx induced by EGF or ZP was completely blocked by U0126. Thus, it has been established that the increase in ERK1/2 phosphorylation/activation in response to ZP or by activation of the EGF receptor (EGFR) by EGF, is a key event for intracellular Ca2+ elevation and the subsequent occurrence of the acrosome reaction.

Keywords

Acrosome reactionCa influxERKFertilizationSperm
Type
Research Article
Information
Zygote , Volume 23 , Issue 5 , October 2015 , pp. 652 - 661
Copyright
Copyright © Cambridge University Press 2014 

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