Molecular Basis of Human Sperm Capacitation

Abstract

In the early 1950s, Austin and Chang independently described the changes that are required for the sperm to fertilize oocytes in vivo. These changes were originally grouped under name of "capacitation" and were the first step in the development of in vitro fertilization (IVF) in humans. Following these initial and fundamental findings, a remarkable number of observations led to characterization of the molecular steps behind this process. The discovery of certain sperm-specific molecules and the possibility to record ion currents through patch-clamp approaches helped to integrate the initial biochemical observation with the activity of ion channels. This is of particular importance in the male gamete due to the fact that sperm are transcriptionally inactive. Therefore, sperm must control all these changes that occur during their transit through the male and female reproductive tracts by complex signaling cascades that include post-translational modifications. This review is focused on the principal molecular mechanisms that govern human sperm capacitation with particular emphasis on comparing all the reported pieces of evidence with the mouse model.

Keywords: acrosomal exocytosis; capacitation; fertilization; human sperm; hyperactivation.

Figure 1

Simplified model of signaling pathways an ion fluxes involved in human sperm capacitation. Na⁺/K⁺ ATPase, Na⁺/K⁺ pump ATPase; SLO1 and 3, sperm-specific K⁺ channel 1 and 3; ENaC, epithelial Na⁺ channels; CFTR, cystic fibrosis transmembrane conductance channel; SLC26, solute carrier 26, there is still no evidence of A3 and A6 is present in mature human sperm; Hv1, voltage-gated H⁺ channels; BSA, bovine serum albumin; CHO, cholesterol; CA, carbonic anhydrase; PYK2/FER, proline-rich tyrosine kinase 2; ADCY10, atypical soluble adenylyl cyclase 10; EPAC, exchange protein activated by cAMP; CaM, calmodulin; CatSper, sperm-specific Ca²⁺ channel; NCX, Na⁺/Ca²⁺-exchanger; PMCA Plasma Membrane Ca²⁺ ATPase; PG, progesterone; ABDH2, α/β hydrolase domain–containing protein 2; 2-AG, 2-Arachidonoylglycerol; AA, arachidonic acid; G, glycerol.