Genetics and Pathophysiology of human asthenozoospermia

Projet de stage : situation du sujet, objectif du stage, approches expérimentales

Infertility is a major public health issue currently affecting an estimated 7%–12% of couples worldwide. Various sperm defects, including asthenozoospermia (defined by the absence or the reduction of sperm motility) are responsible for male infertility. Asthenozoospermia is detected in more than 40% of infertile men and is often associated with lower levels of sperm production and morphological abnormalities (oligo-astheno-teratozoospermia). Despite its high prevalence, very little is known about the genetic abnormalities potentially underlying human asthenozoospermia. During the last years our laboratory has been interested in the molecular mechanisms underlying the process of sperm motility and the pathophysiological events associated with asthenozoospermia. Sperm motility is activated during the transit of the sperm in the epidydimis and relies on a fine regulation of ion exchanges across the plasma membrane. In particular, chloride, bicarbonate and calcium influxes are essential to activate sperm motility and to confer the fertilization potential. We have recently identified the sperm specific protein SLC26A8 as an anion exchanger essential for the activation of the sperm motility. Hence we have shown that SLC26A8 cooperates with the chloride channel CFTR and is essential for sperm motility and male fertility in both mouse and human. The internship we propose aims at identifying further genes required for the control of sperm motility and characterizing the molecular mechanisms that are implicated. The program involves a broad range of technics in the field of genetics and cellular biology (molecular biology, biochemistry, cell culture, immunohistochemistry).

Techniques mises en œuvre par le stagiaire :

Biologie moléculaire, biochimie, culture cellulaire , Immuno-histochimie, microscopie photonique et confocale.