Reproduction Abstracts

Catsper is a Ca²⁺ permeable ion channel in the principal piece of the sperm flagellum that is crucial in regulation of motility. It is multimodally sensitive, being activated by voltage, pHi and diverse agonists including progesterone. Elevation of pHi and progesterone both shift voltage-sensitivity of the channel to more negative potentials and thus may act synergistically to enhance Ca²⁺-influx.¹ However, intracellular alkalinisation of human sperm with NH₄Cl did not enhance the [Ca²⁺]_i response to progesterone.² We have investigated the interaction of the effects of progesterone and extracellular pH (pH 7.4 and 8.5) on hyperactivaton of human sperm, assessed using CASA (Hamilton-Thorne CEROS). At pH 7.4, progesterone increased sperm velocity but stimulated hyperactivation only weakly, in a dose-independent manner (concentration range 0.1–20 μM). At pH 8.5 (buffered with TAPS), ‘control’ levels of hyperactivation were increased fivefold (from 2.5±0.66 to 12.29±1.82%), n=21, P=2×10⁻⁶) but when progesterone was applied the effect on hyperactivation was unchanged and sperm velocity decreased. At both pH 7.4 and 8.5 the effect of progesterone was inversely proportional to the spontaneous level of hyperactivation. These data confirm that activation of Catsper by progesterone only weakly enhances hyperactivation and that alkalinisation does not interact synergistically with progesterone to enhance hyperactivation of human sperm. The effect of pH 8.5 on hyperactivation may involve factors other than CatSper activation.

References: 1. Lishko et al. Nature 471 387–391, 2011.

2. Fraire-Zamora & Gonzalez-Martinez. Am J Physiol Cell Physiol 287 C1688–C1696, 2004.