Cristian Marcel O'Flaherty, DVM, PhD

Research Focus: 

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 and nitric oxide, have 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.
Our research program is designed to identify signal transduction mechanisms modulated by ROS during spermatogenesis, epididymal sperm maturation and then in mature spermatozoa for the acquisition of fertility. Particularly, we are interested in the modulation of gene expression, transcription and post-translational protein modifications by ROS. These studies will bring a better understanding of the pathophysiology of male infertility and lead to the development of novel both diagnostic and therapeutic approaches to help men with idiopathic infertility and cancer patients that are facing infertility problems due to the chemotherapy.

Keywords: 
Reactive oxygen species, oxidative stress, spermatozoa, sperm capacitation, acrosome reaction, male infertility, varicocele, idiopathic infertility
Location: 
Royal Victoria Hospital
Publications:
de Lamirande E, O’Flaherty C. Sperm capacitation as a mild oxidative event. In: “Oxidative Stress and Male Infertility”. Ashok Agarwal, John Aitken and Juan Alvarez (Eds). Humana Press, Springer Science, in press; 2011
O’Flaherty C, Rico de Souza A. Hydrogen Peroxide Modifies Human Sperm Peroxiredoxins in a Dose-Dependent Manner. Biol Reprod 84:238-247; 2011
O'Flaherty C, Hales BF, Chan P, Robaire B. Impact of chemotherapeutics and advanced testicular cancer or Hodgkin lymphoma on sperm deoxyribonucleic acid integrity. Fertil Steril. 94:1374-1379; 2010