Calcium Channel CatSper is a Non-Genomic Progesterone Receptor of Human Sperm

Elevation of intracellular Ca2+ regulate sperm motility, chemotaxis, capacitation and the acrosome reaction, and play a vital role in the ability of the sperm cell to reach and fertilize the egg. In mammalian spermatozoa, the flagellar pH-dependent Ca2+ channel CatSper is the main pathway for calcium entry as measured by the whole-cell patch clamp technique. Mouse CatSper channel is activated by alkaline intracellular pH, but human CatSper requires also a ligand. By applying the patch-clamp technique to mature human spermatozoa, we found that nanomolar concentrations of female hormone progesterone activate CatSper and this action explains the mechanism of non-genomic action of progesterone on human sperm cells. Progesterone is released by cumulus cells surrounding the oocyte and serves as a chemoattractant for human spermatozoa.Interestingly, human CatSper can be further potentiated by prostaglandins, but apparently through a binding site other than that of progesterone. Behavior of CatSper channel gradually changes during spermiogenesis with CatSper channel being fully operational only in mature spermatozoa. Physiological regulation of CatSper channel by different components of seminal plasma as well as hormones of female reproductive tract will be discussed.