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Updated: May 11, 2026

Medium-throughput Screening Assays for Assessment of Effects on Ca2+-Signaling and Acrosome Reaction in Human Sperm
Published on: March 1, 2019
Progesterone utilizes the PI3K-AKT pathway in human spermatozoa to regulate motility and hyperactivation but not
Vrushali Sagare-Patil1, Manvi Vernekar, Mosami Galvankar
1Molecular and Cellular Biology Laboratory, National Institute for Research in Reproductive Health, Indian Council of Medical Research, JM Street, Parel, Mumbai 400 012, India.
Abstract:
Progesterone is a physiologic regulator of sperm hyperactivation and acrosome reaction and it does so by activating a range of kinases present in the spermatozoa. In the present study, the involvement of the AKT- phosphatidylinositol 3-kinase (PI3K) signaling pathway in mediating progesterone response in human spermatozoa was investigated. In capacitated spermatozoa, progesterone transiently and concentration dependently lead to phosphorylation of AKT at both Thr 308 and Ser 473 in the tail region. This phosphorylation was inhibited by the PI3K inhibitor wortmannin, suggesting that progesterone leads to activation of PI3K-AKT pathway. The activation of AKT in response to progesterone is calcium dependent and the CatSper channel inhibitor mibefradil significantly reduced progesterone mediated AKT phosphorylation. Preincubation of spermatozoa with wortmannin inhibited the progesterone mediated increase in tyrosine phosphorylation and also attenuated the increase in number of motile, progressively motile and hyperactive spermatozoa but not the number of acrosome reacted spermatozoa. These observations imply that progesterone via CatSper activates the PI3K-AKT pathway required for motility and hyperactivation but not for acrosome reaction.
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