Progesterone, spermatozoa and reproduction: An updated review

The rapid effects of steroids on spermatozoa have been demonstrated for the first time more than three decades ago. Progesterone (P), which is present throughout the female genital tract with peaks of levels in the cumulus matrix surrounding the oocyte, has been shown to stimulate several sperm functions in vitro, including capacitation, hyperactivation, chemotaxis and acrosome reaction (AR). Besides an increase of intracellular calcium, P has been shown to activate other sperm signalling pathways including tyrosine phosphorylation of several sperm proteins. All these effects are mediated by extra-nuclear pathways likely involving interaction with molecules present on the sperm surface. In particular, the increase in intracellular calcium ([Ca²⁺]_i) in spermatozoa from human and several other mammalian species is mediated by the sperm specific calcium channel CatSper, whose expression and function are required for sperm hyperactive motility. P-mediated CatSper activation is indeed involved in promoting sperm hyperactivation, but the involvement of this channel in other P-stimulated sperm functions, such as AR and chemotaxis, is less clear and further studies are required to disclose all the involved pathways. In human spermatozoa, responsiveness to P in terms of [Ca²⁺]_i increase and AR is highly related to sperm fertilizing ability in vitro, suggesting that the steroid is a physiological inducer of AR during in vitro fertilization. In view of their physiological relevance, P-stimulated sperm functions are currently investigated to develop new tools to select highly performant spermatozoa for assisted reproduction.