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Updated: Mar 28, 2026

Recording Electrical Currents across the Plasma Membrane of Mammalian Sperm Cells
Published on: February 14, 2021
The Fungal Sexual Pheromone Sirenin Activates the Human CatSper Channel Complex
Shameem Sultana Syeda1, Erick J Carlson1, Melissa R Miller2,3
1Department of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota , Minneapolis, Minnesota 55414, United States.
Abstract:
The basal fungus Allomyces macrogynus (A. macrogynus) produces motile male gametes displaying well-studied chemotaxis toward their female counterparts. This chemotaxis is driven by sirenin, a sexual pheromone released by the female gametes. The pheromone evokes a large calcium influx in the motile gametes, which could proceed through the cation channel of sperm (CatSper) complex. Herein, we report the total synthesis of sirenin in 10 steps and 8% overall yield and show that the synthetic pheromone activates the CatSper channel complex, indicated by a concentration-dependent increase in intracellular calcium in human sperm. Sirenin activation of the CatSper channel was confirmed using whole-cell patch clamp electrophysiology with human sperm. Based on this proficient synthetic route and confirmed activation of CatSper, analogues of sirenin can be designed as blockers of the CatSper channel that could provide male contraceptive agents.
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