Progesterone Accelerates the Completion of Sperm Capacitation and Activates CatSper Channel in Spermatozoa from the Rhesus Macaque1

Abstract

During transit through the female reproductive tract, mammalian spermatozoa are exposed to increasing concentrations of progesterone (P4) released by the cumulus oophorus. P4 triggers massive calcium influx into human sperm through activation of the sperm-specific calcium channel CatSper. These properties of human spermatozoa are thought to be unique since CatSper is not progesterone sensitive in rodent sperm. Here, by performing patch clamp recording from spermatozoa from rhesus macaque for the first time, we report that they express P4-sensitive CatSper channel identically to human sperm and react to P4 by inducing responsiveness to zona pellucida, unlike human sperm, which respond directly to P4. We have also determined the physiologic levels of P4 capable of inducing capacitation-associated changes in macaque sperm. Progesterone (1 μM) induced up to a 3-fold increase in the percentage of sperm undergoing the zona pellucida-induced acrosome reaction with the lowest threshold as low as 10 nM of P4. Submicromolar levels of P4 induced a dose-dependent increase in curvilinear velocity and lateral head displacement, while sperm protein tyrosine phosphorylation was not altered. Macaque spermatozoa exposed to 10 μM of P4 developed fully hyperactivated motility. Similar to human sperm, on approaching cumulus mass and binding to zona pellucida, macaque spermatozoa display hyperactivation and undergo an acrosome reaction that coincides with the rise in the sperm intracellular calcium. Taken together, these data indicate that P4 accelerates the completion of capacitation and provides evidence of spermatozoa "priming" as they move into a gradient of progesterone in search for the oocyte.

Effects of CXCL12/CXCR4/CXCR7 axis on human sperm motility and chemotaxis

“…Furthermore, the results of sperm motility showed that only the VCL in all parameters increased significantly after CXCL12 treatment, which was consistent with the findings in other studies that not all kinetics parameters had significant changes (Sumigama et al, 2015;Armon and Eisenbach, 2011). As an important symbol of sperm motility, VCL is also a representative of hyperactivation (Rovasio, 1998; Suarez and Dai, 1992).…”

Sperm Capacitation and Acrosome Reaction in Mammalian Sperm

“…These measurements were able to conclusively demonstrate using solid electrophysiological tools the presence of CatSper, SLO3, and Hv1 in mammalian sperm from different species (Kirichok et al 2006;Navarro et al 2007;Strunker et al 2011;Brenker et al 2012Brenker et al , 2014Sumigama et al 2015). However, T channel currents from Cav 3.2 which are readily observed in testicular sperm cells (Arnoult et al 1996;Lievano et al 1996;Publicover and Barratt 1999;Martinez-Lopez et al 2009) cannot be detected in epididymal sperm.…”

The progesterone‐induced sperm acrosome reaction is a good option for the prediction of fertilization in vitro compared with other sperm parameters

“…The A23187‐induced AR mainly involves a chemical effect on membrane fusion and the induced Ca 2+ influx through bypasses other than Ca 2+ channels (Tateno et al, ; Yuan et al, ), whereas the physiological AR involves activation of several signal transduction pathways. Recently, the sperm‐specific CatSper channel was shown to have a major role in the mechanism of P 4 ‐induced Ca 2+ influx and the sperm AR (Strunker et al, ; Sumigama et al, ; Tamburrino et al, ).…”