Cristian O’Flaherty, DVM, PhD

We are interested in the molecular mechanisms that drive the production of mature spermatozoa and their modulation by reactive oxygen species (ROS). These active molecules, such as superoxide, hydrogen peroxide, nitric oxide, and peroxynitrite have a dual effect on cellular metabolism. The oxidative stress, a condition characterized by high levels of ROS and/or low levels of antioxidant systems, can induce damage on spermatogenesis and sperm maturation, leading to an increase of defects in the sperm genetic information, motility machinery and the acquisition of fertilizing ability by the spermatozoon.

On the other hand, when ROS are produced in low and physiological conditions, they trigger and modulate signaling events that allow the spermatozoon to have fertilizing competence.

Little is known regarding the molecular mechanisms affected by oxidative stress and how ROS can disturb the machinery to produce spermatozoa.

Our main research interest is to study the role of ROS in male reproduction. Peroxiredoxins (PRDXs) are enzymes with a dual role as antioxidants and as modulators of ROS action. PRDXs are differentially localized in sperm compartments, and they react with ROS, thus being potential candidates for modulators of ROS action in sperm physiology. Prdx6^-/- males are infertile, and they have spermatozoa with low motility and unable to fertilize an oocyte. Interestingly, these abnormal reproductive outcomes worsen with age. PRDXs control the levels of ROS in spermatozoa to avoid their toxic effects when produced at high concentration in the cell. Dysregulation of the PRDX system promotes impairment of motility and viability and the inability of spermatozoa to acquire fertilizing ability. Lack of PRDXs in spermatozoa has been associated with men infertility.

We are also focused on the impact of oxidative stress on mammalian spermatozoa. ROS promote oxidative modifications (thiol oxidation, tyrosine nitration, carbonylation, sulfonation, etc.) in sperm proteins that are associated with impairment of sperm viability, motility, and abnormal sperm chromatin, and fertilizing ability in rodents and humans. Our research is funded by CIHR.

John Calogerinis
Undergraduate student (Honorous program)
john.calogerinis@mail.mcgill.ca

Diego Loggia
MSc candidate
diego.loggia@mail.mcgill.ca

Chika Onochie
MSc candidate
chika.onochie@mail.mcgill.ca

Caleb Liao
MSc student
hao-yu.liao@mail.mcgill.ca

Steven Serafini
PhD candidate
steven.serafini@mail.mcgill.ca