Cristian O'Flaherty, DVM, PhD
andrology • male infertility • oxidative stress • redox signaling • toxicology
My interest focuses on the molecular mechanisms that drive the production of mature spermatozoa and their modulation by reactive oxygen species (ROS). The oxidative stress (OS), 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 paternal genome and impairment of motility and the acquisition of fertilizing ability by the spermatozoon. On the other hand, low ROS levels trigger and modulate signaling pathway necessary for the spermatozoon to achieve fertilizing competence. We aim to identify molecular mechanisms modulated by ROS during spermatogenesis, epididymal sperm maturation and capacitation. We recently characterized a newly discovered family of antioxidant enzymes called Peroxiredoxins (PRDXs) that play a major role in the protection of human spermatozoa against OS. Reduced activity or absence of PRDXs are associated with male infertility. Our ultimate goal is to develop novel diagnostic and therapeutic approaches to help infertile men.
Gong S, San Gabriel M, Zini A, Chan P, O'Flaherty C. Low amounts and high thiol oxidation of peroxiredoxins in spermatozoa from infertile men. J Androl, 33:1342-51, 2012.
O'Flaherty C, Rico de Souza A. Hydrogen peroxide modifies human sperm peroxiredoxins in a dose-dependent manner. Biol Reprod 84:238-247, 2011.
de Lamirande E, O'Flaherty C. Sperm capacitation as an oxidative event. In: "Studies on men's health and fertility, oxidative stress in applied basic research and clinical practice". Ashok Agarwal, John Aitken and Juan Alvarez (Editors). Humana Press, Springer Science, pp 57-94 2012.
O'Flaherty C. Iatrogenic Genetic damage of spermatozoa. In: "Genetic damage in human spermatozoa. Advances in experimental medicine and biology, vol 791. Elisabetta Baldi and Monica Muratori (eds). Springer Science, pp. 117-135, 2013.
O'Flaherty C, Hales B, Chan P, Robaire B. Sperm chromatin structure components are differentially repaired in cancer survivors. J Androl 33:629-636, 2012.