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Cristian O’Flaherty, D.V.M. Ph.D.

Assistant professor

McGill University – MUHC

Department of Surgery (Division of Urology)

Royal Victoria Hospital

Urology Research Laboratory room H6.46

687 Ave des Pins Ouest

H3A 1A1 Montreal, QC

Phone: 514-934-1934 ext.: 35410

Fax: 514-843-145

E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

   

Research Interests:

  • Role of reactive oxygen species in male reproduction
  • Redox regulation of signaling
  • Spermatogenesis
  • Epididymal maturation
  • Sperm activation (motility, capacitation and acrosome reaction)
  • Semen cryopreservation
  • Male infertility

 

Summary of Results:

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 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.

We are currently elucidating the role of peroxiredoxins (PRDXs) in male reproduction. 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. Our research is funded by CIHR.

 

Lab Members:

Name

Position

Email address

Burak Ozkosem

PhD student

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 David Matsushita-Fournier

MSc studient 

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List of publications:

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.

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, de Lamirande E, Leclerc P, Lefievre L, Robaire B. In memoriam: Claude Gagnon, PhD, 1950-2012. Biol Reprod. 87:50, 1–1, 2012.

O'Flaherty C, de Lamirande E, Leclerc P, Lefievre L, Robaire B. Memorial: Claude Gagnon, Ph.D. (1950-2012). J Androl 33:1125-1126, 2012. Free article @ PubMed.

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, Hales B, Chan P, Robaire B. Sperm Chromatin Structure Components Are Differentially Repaired in Cancer Survivors. J Androl, 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. 

Bedard N, Yang Y, Gregory M, Cyr D, Suzuki J, Yu X, Clarke H, Chian R, Hermo L, O’Flaherty C, Smith C, Wing S. Mice Lacking the USP2 Deubiquitinating Enzyme have Severe Male Sub-Fertility Associated with Defects in Fertilization and Sperm Motility. Biol Reprod, 85:594-604, 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 94:1374-9; 2010.

O'Flaherty C, Vaisheva F, Hales BF, Chan P, Robaire B. Characterization of sperm chromatin quality in testicular cancer and Hodgkin's lymphoma patients prior to chemotherapy. Hum Reprod 23:1044-52; 2008.

de Lamirande E, O'Flaherty C. Sperm activation: role of reactive oxygen species and kinases. Biochim Biophys Acta 1784:106-15; 2008.

O'Flaherty C, de Lamirande E, Gagnon C. Positive role of reactive oxygen species in mammalian sperm capacitation: triggering and modulation of phosphorylation events. Free Radic Biol Med 41:528-40; 2006.

O'Flaherty C, de Lamirande E, Gagnon C. Reactive oxygen species modulate independent protein phosphorylation pathways during human sperm capacitation. Free Radic Biol Med 40:1045-55; 2006.

O'Flaherty C, Beorlegui N, Beconi MT. Heparin- and superoxide anion-dependent capacitation of cryopreserved bovine spermatozoa: requirement of dehydrogenases and protein kinases. Free Radic Res 40:427-32; 2006.

O'Flaherty C, Breininger E, Beorlegui N, Beconi MT. Acrosome reaction in bovine spermatozoa: role of reactive oxygen species and lactate dehydrogenase C4. Biochim Biophys Acta 1726:96-101; 2005.

Breininger E, Beorlegui NB, O'Flaherty CM, Beconi MT. Alpha-tocopherol improves biochemical and dynamic parameters in cryopreserved boar semen. Theriogenology 63:2126-35; 2005.

O'Flaherty C, de Lamirande E, Gagnon C. Reactive oxygen species and protein kinases modulate the level of phospho-MEK-like proteins during human sperm capacitation. Biol Reprod 73:94-105; 2005.

Cassani P, Beconi MT, O'Flaherty C. Relationship between total superoxide dismutase activity with lipid peroxidation, dynamics and morphological parameters in canine semen. Anim Reprod Sci 86:163-73; 2005.

Rodriguez PC, O'Flaherty CM, Beconi MT, Beorlegui NB. Nitric oxide-induced capacitation of cryopreserved bull spermatozoa and assessment of participating regulatory pathways. Anim Reprod Sci 85:231-42; 2005.

O'Flaherty C, Rodriguez P, Srivastava S. L-arginine promotes capacitation and acrosome reaction in cryopreserved bovine spermatozoa. Biochim Biophys Acta 1674:215-21; 2004.

O'Flaherty C, de Lamirande E, Gagnon C. Phosphorylation of the Arginine-X-X-(Serine/Threonine) motif in human sperm proteins during capacitation: modulation and protein kinase A dependency. Mol Hum Reprod 10:355-63; 2004.

O'Flaherty C, Beorlegui N, Beconi MT. Participation of superoxide anion in the capacitation of cryopreserved bovine sperm. Int J Androl 26:109-14; 2003.

O’Flaherty C, Beorlegui N, Beconi M. Role of superoxide anion and hydrogen peroxide in bovine acrosome reaction”. In Andrology in the 21st Century. Proceedings of the VII International Congress of Andrology. B Robaire, H Chemes, C Morales (eds), Medimond Publications, pp. 103-108, 2001.

O'Flaherty CM, Beorlegui NB, Beconi MT. Reactive oxygen species requirements for bovine sperm capacitation and acrosome reaction. Theriogenology 52:289-301; 1999.

 

Awards:

C O’Flaherty : FRSQ, Bourses de chercheurs boursiers, Fondamental

B Ozkosem : CREATE studentship, FRBM travel award.