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      cyr      

Daniel Cyr, Ph.D

Professor

Institut National de la Recherche Scientifique

Institut Armand-Frappier

531 boulevard des Prairies

Laval (Québec)  H7V 1B7

Phone:  (450) 687-5010 ext 8833

Fax : (450) 686-5510

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Research Interests:

Our laboratory is interested in understanding the role of cell-cell interactions in the epididymis and their importance in creating a luminal environment suitable for sperm maturation. We are also interested in the effects of environmental toxicants on cell-cell interaction and in the development and male reproductive function.

 

Summary of Results:

 

REGULATION OF INTERCELLULAR COMMUNICATION 

Intercellular gap junctions are essential structural components that allow direct communication between neighboring cells. Gap junctional communication is therefore critical for coordinating cellular function within complex epithelia. In the male reproductive tract, gap junctional communication is essential for the exchange of cellular messengers necessary for spermatogenesis in the testis and for the coordination of sperm maturation in the epididymis. The regulation of gap junctions is therefore essential for male fertility. Our research objectives are to understand the regulation of connexins in both the testis and epididymis as these relate to male fertility.

 

EPIDIDYMAL TIGHT JUNCTIONS AND THE BLOOD-EPIDIDYMAL BARRIER

It is estimated that there are 300 000 infertile couples in Canada. More than half of these are related to problems associated with male reproductive dysfunction. Of those, 40% occur from idiopathic or unexplained causes and only 11% of patients can be treated for their infertility. While spermatozoa are formed in the testis, testicular spermatozoa are immature and cannot swim or fertilize. These critical spermatozoal functions are acquired in the epididymis, where a specific luminal environment is created by the blood-epididymal barrier. Proteins secreted by epididymal principal cells bind to maturing spermatozoa and regulate the maturational process of the spermatozoa. While we have made significant progress in understanding epididymal function and the blood-epididymal barrier using animal models, there is limited information on the human epididymis. If we are to understand the normal and pathological conditions attributable to human epididymal function, we must clearly establish the physiological, cellular and molecular regulation of the human epididymis, develop tools to characterize these functions and develop clinical strategies that will target epididymal functions to improve treatment of infertility. Our research is focused on two critical aspects of human epididymal physiology: the molecular regulation of the tight junctions, which make up the blood-epididymal barrier, and the regulation of epididymal spermatozoal maturation. To address these issues we intend to develop tools to assess and better understand human epididymal function and use the results in developing novel clinical strategies in the treatment of male infertility.

 

EFFECTS OF ENDOCRINE DISRUPTORS ON MALE REPRODUCTION

We have shown that fish in the St. Lawrence River are exposed to environmental estrogens. This contamination originates in the Ottawa River. Other sources of estrogenic contamination include the Montreal Urban Community’s sewage effluent. Contamination of aquatic ecosystems by estrogenic substances can be associated with a variety of chemical contaminants, and in particular the alkylphenol exthoxylates. Using the rodent model we have shown that the consumption of fish from the St. Lawrence is associated with a decrease in sperm quality. This decrease is associated with a loss of cellular junctions in the testis. Our research is focused on determining the effects of environmental toxicants on the expression and regulation of cellular junctions in the male reproductive tract and to understand the potential risk that these contaminants pose to human health.

 

Laboratory Members: 

Name

Position

Email Address

Julie Dufresne 

Research Assistant

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Mary Gregory  

Research Assistant

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Marion Mandon           

PhD Student    

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Cécile Adams  

PhD Student

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Raheleh Aram

PhD Student    

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Bintou Gaye

Master Student

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List of Publications (2008-2014)

 

Cyr DG. 2014. Male reproductive toxicology and the role of immunohistochemistry. In ‘Toxicological Immunohistochemistry’ S. Aziz ed. Springer, New York (in press)

 

Cyr DG, Devine PJ and Plante I. 2014. Immunhistochemistry and female reproductive toxicology: The ovary and mammary glands. In ‘Toxicological Immunohistochemistry’ S. Aziz ed. Springer, New York (in press)

Cyr DG, Lee KH, Marcogliese DJ, and Sanderson JT. 2013. Recent advances in endocrine disruptors. In ‘Encyclopedia of Aquatic Toxicology’, C. Blaise, JF Ferrard eds. Elsevier, New York. vol. 2, pp781-796.

 

Christin MS, Ménard L, Giroux I, Brousseau P, Marcogliese DJ, Ruby S, Cyr D, and Fournier M. 2013. Effects of agricultural pesticides on the health of leopard frogs (Rana pipiens) sampled from the field. Environ Poll Res Int. 20, 601-611

Dubé É, Dufresne J, Chan PTK and Cyr DG. 2012. Male infertility and the expression of connexin43 and 32: Role of the epididermal growth factor receptor, ERK and AKT signalling. Human Reprod 27, 2285-2296

 

Belleannée C, Calvo E, Thimon V, Cyr DG, Légaré C, Garneau L, and   Sullivan R. 2012. Role of microRNAs on the pattern of gene expression in the different segments of human epididymis. PLoS One 7, e34996.

 

Dubé É and Cyr DG. 2012. The Blood-Epididymis Barrier. In ‘Biology and Regulation of Blood-Tissue Barriers’, C.Y. Cheng ed. Landes Bioscience, New York, NY. Pp 218-236.

 

Cyr DG. 2011. Connexins and pannexins: Intercellular communiciation in the male reproductive tract. Spermatogenesis 1, 325-338.

Cyr DG, Dubé E, Dufresne J, and Gregory M. 2011. Development of biological tools to study claudins in the male reproductive tract. In “Claudins: Methods and Protocols” K. Turksen ed. Springer Humana Press. New York. . Pp 259-273

 

Gregory M, Kahiri CNK, Barr KJ, Smith CE, Liu L, Hermo L, Cyr DG, and Kidder GM. 2011. Male reproductive system defects and subfertility in a mutant mouse model of oculodentodigital dysplasia. Int J Androl 34, e630–e641

Bedard N, Yang Y, Gregory M, Cyr DG, Suzuki J, Yu X, Clarke H, Chian RH, Hermo L, O’Flaherty C, Smith CE and Wing SS. 2011. Mice lacking the USP2 deubiquitinating enzyme have severe sub-fertility associated with a defect in sperm motility Biol Reprod 85:594-604

 

Turmel P, Dufresne J, Hermo L, Smith CE, Penuela S, Laird DW, and Cyr DG. 2011. Characterization and regulation of pannexin-1 and pannexin-3 in the male reproductive tract of the adult rat Mol Reprod Dev 78, 124-138.

 

Jones S and Cyr DG. 2011. Regulation and characterization of the ATP-binding cassette transporter-B1 in the epididymis and epididymal spermatozoa of the rat. Toxicol Sci 119, 369-379.

 

De Montgolfier B., Audet C., and Cyr DG. 2011. Characterization of the testicular cx43 promoter in the brook trout: Regulation by thyroid hormones and cAMP. Gen Comp Endocrinol 170:110-118

 

Cyr DG and Nagler JJ. 2010. Cellular interactions and spermatogenesis in the fish testis. In Recent Advances in Fish Reproductive Biology. A Garcia Ayala, JM Penalver, E Chaves-Ponzo eds. Research Signpost Publications, Kerala, India, pp109-126.

Dubé E, Chan P, Hermo L and Cyr DG. 2010. Alterations in the human blood-epididymis barrier in obstructive azoospermia and the development of novel epididymal cell lines from infertile men Biol Reprod 83, 584-596

 

Ménard L, Escarné R, Marcogliese DJ, Cyr DG, Fournier M and Gagné F. 2010. Large scale impacts of urban pollution to the immune system of spottail shiners (Notropis hudsonius). Fresnius Environ. Bull. 19, 1369-1374.

Dubé E, Chan P, Hermo L and Cyr DG. 2010. Assessing the role of claudins in maintaining the integrity of epididymal tight junctions using novel human epididymal cell lines. Biol Reprod 82,1119-1128.

 

Wai T, Ao A, Zhang X, Cyr D, Dufort, and Shoubridge EA. 2010. The Role of Mitochondrial DNA Copy Number in Mammalian Fertility. Biol Reprod. 83, 52-62.

Muller C, Ruby S, Brousseau P, Cyr D, Fournier M, Gagné F. 2009. Immunotoxicological effects of an activated-sludge-treated effluent on rainbow trout (Oncorhynchus mykiss). Comp Biochem Physiol, Part C 150, 390–394.

 

Sahambi SK, Tardif R, Pelland A, Cooke GM, Schrader T, Charbonneau M, Krishnan K, Haddad S, Cyr DG, Devine PJ. 2010. Oral p-tert-octylphenol exposures induce toxic but not estrogenic effects in adult female rats. J Toxicol Environ Health A73, 607 – 622.

 

Foster WG, Maharaj S, and Cyr DG. 2010. Mechanisms of dioxin action on the male : spermatogenesis versus epididymal sperm counts. Env Health Persp 118, 458-464.

 

Hermo, L, Pelletier RM, Cyr DG and Smith C. 2010. Surfing the Wave, Cycle, Life History and Genes/Proteins Expressed by Testicular Germ Cells. Part 1: Background to Spermatogenesis, Spermatogonia and Spermatocytes. Micros. Res. Tech 73:241-78

Hermo, L, Pelletier M, Cyr DG and Smith C. 2010. Surfing the Wave, Cycle, Life History and Genes/Proteins Expressed by Testicular Germ Cells.the wave, cycle, life history and proteins expressed by germ cells Part 2: Changes in Spermatid Organelles Associated with Development of Spermatozoa Micros. Res. Tech 73:279-319

 

Hermo, L, Pelletier M, Cyr DG and Smith C. 2010. Surfing the Wave, Cycle, Life History and Genes/Proteins Expressed by Testicular Germ Cells.the wave, cycle, life history and proteins expressed by germ cells Part 3: Developmental Changes in Spermatid Flagellum and Cytoplasmic Droplet and Interaction of Sperm with the Zona Pellucida and Oocyte Plasma Membrane Micros. Res. Tech 73:320-63

 

Hermo, L, Pelletier M, Cyr DG and Smith C. 2010. Surfing the Wave, Cycle, Life History and Genes/Proteins Expressed by Testicular Germ Cells.the wave, cycle, life history and proteins expressed by germ cells Part 4: Intercellular Bridges, Mitochondria, Nuclear Envelope, Apoptosis, Ubiquitination, Membrane/Voltage-gated Channels, Methylation/Acetylation and Transcription Factors. Micros. Res. Tech 73:364-408.

 

Hermo, L, Pelletier M, Cyr DG and Smith C. 2010. Surfing the Wave, Cycle, Life History and Genes/Proteins Expressed by Testicular Germ Cells.the wave, cycle, life history and proteins expressed by germ cells Part 5: Intercellular Junctions and Contacts between Germs Cells and Sertoli Cells and Their Regulatory Interactions, Testicular Cholesterol, and Genes/Proteins Associated With More than One Germ Cell Generation. Micros. Res. Tech 73:409-94

 

Gregory M, Lacroix A, Haddad S, Devine P, Charbonneau M, Tardif R, Krishnan K, Cooke G, Schrader T, and Cyr DG. 2009. Effects of long-term exposure to octylphenol on the male reproductive system of the rat. J Toxicol Environ Health A. 72, 1553-1560.

 

Hamelin, D, Haddad, S., Krishnan, K., Cyr D.G., Devine, P.J., Charbonneau, M., and Tardif, R. 2009. Toxicokinetics of p-tert-octylphenol in male and female Sprague-Dawley rats after intravenous, oral and subcutaneous exposure.  J Toxicol Environ Health A. 72: 541– 550

de Montgolfier B, Faye A, Audet C, and Cyr DG. 2009. Seasonal variations and regulation of testicular connexins in brook trout, Savelinus fontinalis. Gen. Comp. Endocrinol. 162: 276-285

 

Hébert N, Gagné F, Cyr D, Pellerin J, Blaise C, and Fournier M. 2009. Effects of 4-nonylphenol on the immune system of rainbow trout (Oncorhynchus mykiss). Fresnius Environ. Bull. 18, 757-761.

 

Escarné R, Gagné F, Dautremepuits C, Cyr DG, Finnson K, Marcogliese DJ, Bernier J, Cejka P, and Fournier M. 2009 Effects of municipal sewage effluent on non-specific immune and thyroid functions of rainbow trout (Onchorynchus mykiss). Trends. Comp. Physiol. Biochem. 13, 27-39.

Gregory M, Aravindakshan J, Nadzialeck S and. Cyr DG, 2008. Effects of endocrine disrupting chemicals on male reproduction. In H. Alavi, R. Raffiee, J Cosson, and K. Coward eds. “Fish Spermatology” Narosa Publish House. New Dehli pp 161-214.

 

Hermo L, Chung S, Gregory M, Smith CE, Wang SP, El-Alfy M, Cyr DG, Mitchell GA , and Trasler JM. 2008. Alterations in the testis of hormone sensitive lipase-deficient mice is associated with decreased sperm counts, sperm motility and fertility. Mol Reprod Dev Biol 75, 565-577.

 

Dubé E, Hermo L, Chan PTK, and Cyr DG. 2008. Alterations in gene expression in the caput epididymis of non-obstructive azoospermic men Biol. Reprod. 78, 342-351.

 

Hamelin G, Charest-Tardif G, Krishnan K, Cyr DG, Charbonneau M, Devine P, Haddad S, Cooke GM, Schrader T, and Tardif, R. 2008. Determination of p-tert-octylphenol in blood and tissues by gas chromatography coupled with mass spectrometry. J. Anal. Toxicol. 32:303-307.

 

Iacono NL, Lopardo T, Giustizieri ML, Cyr DG, Crosti F, Costanzo A and Guerrini L. 2008. Claudin-1 is a p63 target gene with a crucial role in epithelial development. PLoS One 3: e2715-2720.

 

Hébert N, Gagné F, Cejka P, Bouchard B, Hausler R, Cyr DG, Blaise C, and Fournier M. 2008. Effects of ozone, ultraviolet and peracetic acid disinfection of a primary-treated municipal effluent on the Immune system of rainbow trout (Oncorhynchus mykiss). Comp. Biochem. Physiol. C Toxicol. Pharmacol. 148, 122-127.

 

Josephy PD and Cyr DG. 2008. Northern exposures, northern risk: Toxicology in Canada. Chem Res Toxicol. 21, 1909-1912.

deMontgolfier B, Fournier M, Audet C, Marcoglise D. and Cyr DG. 2008. Influence of municipal effluents on connexin expression in the brook trout (Salvelinus fontinalis) testis. Aquat. Toxicol. 86, 38-48.

 

King KC, Gendron AD, McLaughlin JD, Giroux I, Brousseau P, Cyr D, Ruby SM, Fournier M, Marcogliese DJ. 2008. Short-term seasonal changes in parasite community structure in Northern leopard froglets (Rana pipiens) from agricultural wetlands in southern Quebec, Canada. J. Parasitol. 94, 13-22.

Hébert N, Gagné F, Cejka P, Cyr D, Marcogliese DJ, Balise C, Pellerin J, and Fournier M. 2008. The effects of a primary-treated municipal effluent on the immune system of rainbow trout (Oncorhynchus mykiss): Exposure duration and contribution of suspended particles. Comp Biochem Physiol C Toxicol Pharmacol. 148:258-264.