Molecular Mechanism for Human Sperm Chemotaxis Mediated by Progesterone

Abstract

Sperm chemotaxis is a chemical guiding mechanism that may orient spermatozoa to the egg surface. A picomolar concentration gradient of Progesterone (P), the main steroidal component secreted by the cumulus cells that surround the egg, attracts human spermatozoa. In order to elucidate the molecular mechanism of sperm chemotaxis mediated by P, we combine the application of different strategies: pharmacological inhibition of signaling molecules, measurements of the concentrations of second messengers and activation of the chemotactic signaling. Our data implicate a number of classic signal transduction pathways in the response and provide a model for the sequence of events, where the tmAC-cAMP-PKA pathway is activated first, followed by protein tyrosine phosphorylation (equatorial band and flagellum) and calcium mobilization (through IP3R and SOC channels), whereas the sGC-cGMP-PKG cascade, is activated later. These events lead to sperm orientation towards the source of the chemoattractant. The finding proposes a molecular mechanism which contributes to the understanding of the signal transduction pathway that takes place in a physiological process as chemotaxis.

Infertility treatment, a matter of a lovely sperm?

“…4,5 Very low doses of progesterone (a steroid secreted by the cells surrounding the oocyte) attract capacitated human spermatozoa. 6,7 By combining the ability of chemotaxis to select good spermatozoa with the use of progesterone as an attractant molecule, a new sperm selection assay (SSA) was recently developed. 8 …”

Human sperm pattern of movement during chemotactic re-orientation towards a progesterone source

“…Next, the highly motile sperm population was adjusted to 6310 6 cells ml 21 in HAM F-10 that had been supplemented with 1% human serum albumin (Laboratorio de Hemoderivados, University of Cordoba, Cordoba, Argentina) and then incubated at 37 uC in 5% CO 2 in air for 4 h, which are conditions that have been established to support sperm capacitation. 14 …”

“…3,[13][14] Briefly, a few drops of culture medium were added over the bridge, and a coverslip was placed upside down on the bridge. First, W2 was filled either with progesterone or the culture medium.…”

“…As an internal control, the proportion of chemotactic spermatozoa was determined for each sample, as previously described. 3,13,14 Only those samples exhibiting a chemotactic response to 10 pmol l 21 progesterone were included in the study.…”

“…7,[13][14][15] The transmembrane adenylyl cyclase-cyclic adenosine mono phosphate-protein kinase A pathway and soluble guanylate cyclase-cyclic guanosine monophosphateprotein kinase G pathway, calcium mobilisation and protein Tyrphosphorylation appear to be involved in the chemotactic response mediated by progesterone. 14 These physiological characteristics of sperm chemotaxis described above, have been primarily observed in human spermatozoa; however, the chemotactic pattern of movement has not been easy to describe. The primary reasons for this are that there are very few chemotactic spermatozoa and that these spermatozoa gradually approximate to the source of the attractant by progressive linear movement.…”