Régulation de la signalisation redox dans la reproduction masculine

 

Cristian O'Flaherty

Université McGill

 

Domaine : Santé différentielle des sexes

Programme chercheurs-boursiers - Junior 2

Concours 2016-2017

Infertility is an important human health problem that affects about 16% of couples worldwide; half of these cases can be traced to men. The diagnosis and treatment of this health problem is difficult because in 37-58% of cases the causes are not known. Infertile men often have high levels of reactive oxygen species (ROS) in their semen; these molecules are normally produced by the cell, but when they are present in high amounts, they become toxic. As men age, spermatogenesis is affected resulting in the production of less spermatozoa with impaired function. Because of professional and/or work priorities, men are planning to have children around or after their 40s. Thus, this deliberated delay may impact negatively on their success to achieve fatherhood or could be the cause of transmitting defects to their children. Spermatozoa, as other cell types, can cope with certain levels of ROS by removing those by antioxidants. However, if the antioxidant amount is low and or the production of ROS is too high, then toxic effects can be observed in the sperm.

This proposal is focused on the role peroxiredoxins (PRDXs) in the protection of the male reproductive tract against the toxic effect of high levels of ROS. Spermatozoa from infertile men have low PRDXs levels; we will further elucidate their role in sperm function using human spermatozoa as well as animal models. Our PRDX6 knockout model is useful to study the impact on fertility. Spermatozoa from these mice males have significant higher levels of sperm DNA damage and oxidation and lower motility than wild type controls.  Understanding the role of PRDXs in spermatozoa under physiological conditions will allow us to seek for therapeutic strategies to keep the levels of ROS at desirable physiological levels in infertile young and aging men seeking fatherhood.