Progesterone Accelerates the Completion of Capacitation and activates CatSper Channel in Spermatozoa from the Rhesus Macaque (#24)
During their transit through female reproductive tract and as they approach an ovulated oocyte, mammalian sperm are exposed to increasing concentrations of progesterone. Progesterone, secreted by the cumulus oophorus, was shown to activate massive calcium influx into human sperm due to activation of the sperm calcium channel CatSper. This unique property of human sperm set them apart from other mammalian species such as rodents and ruminants for which progesterone was not shown to have such an effect. Here, we show for the first time that these sperm react identical to human sperm in terms of their progesterone sensitivity and ion channel repertoire. In addition, we have determined the physiologic levels of progesterone (P4) that are capable of inducing capacitation-associated changes in macaque sperm. Progesterone at 1M concentration induced up to a three-fold increase in the percentage of sperm that undergo the zona pellucida-induced acrosome reaction compared to controls with the lowest threshold as low as just 10 nM of P4. Sub-micromolar levels of P4 also induced a dose-dependent increase in curvilinear velocity and lateral head displacement. However, sperm protein tyrosine phosphorylation was not altered by treatment of sperm with progesterone. At 10 µM of P4 macaque sperm developed fully hyperactivated motility. Changes in the zona pellucida-induced acrosome reaction and sperm motility with progesterone treatment appeared to coincide roughly with changes in sperm intracellular calcium. By performing patch clamp recording from capacitated macaque sperm, we also show that the CatSper channel is present and is progesterone regulated. Taken together, these data indicate that macaque sperm are almost identical in their physiology and molecular regulation to human spermatozoa. This indicates the importance of using rhesus macaque as ideal animal model for studying human male fertility. Collectively, these results demonstrate that progesterone accelerates the completion of capacitation of macaque sperm and suggest that as sperm move into a gradient of progesterone in vivo they become fully primed to interact with the oocyte.