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YTremblay

Yves Tremblay, PhD

Professeur Titulaire

Université Laval, CHUL Research center

Département: Reproduction,

health and Development of the Child

room T3-67

2705 boulevard Laurier, Québec, Québec, G1V 4G2 

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Téléphone: 418-525-4444 extension 46158

Fax: 418-654-2783

 

Field or research:

  • Steroid
  • Lung Development and Physiology
  • Perinatal Research
  • Premature Birth
  • Placental Physiology
  • Respiratory Distress Syndrome in Newborn
  • Bronchopulmonary Dysplasia
  • Gender-Sex-Based-Approach
  • Transdiscipliunary Reflection
  • Molecular Biology
  • Functional genomic

Recent results:

During the last decade, my laboratory have continued to extend my hypothesis of extra gonadal and adrenal steroid production to the fetal lung. Using several approaches we showed that the human fetal lung is an androgen metabolizing organ, where synthesis and inactivation should occur in PTII and in fibroblasts. Using mouse fetal lung, male and female tissue synthesize androgens in correlation with the surge of surfactant synthesis. Androgen synthesis by fetal lung tissue from both sexes in correlation with the emergence of PTII cell, is a novel concept that introduced a new perspective on the role of androgens in fetal lung. This discovery has shifted our paradigm on the control of androgen action during fetal lung development and how to look at its control with respect to respîratory distress syndrome and lung maturation. Nuclear localization of androgen receptor protein during that period confirmed an androgen receptor-dependent mechanism of androgen action. We also demonstrate, that following the surge of surfactant synthesis, androgens are rapidly inactivated in the fetal lung by the 3a-HSD, switching off the androgen receptor . We have proposed that the important increase of 3aHSD being a reliable bioevent of the mature lung. These results are also supported by a regulation of the androgen receptor levels as well as regulation of androgen levels. Beside this new role for androgens, they are responsible for the sex differences that result in a higher incidence of RDS in premature boys. To move forward, an atlas of androgen-dependent genes expressed with a sex difference during the surge in surfactant synthesis was established by microarray DNA profiling. Several metabolisms that are likely to play a role in the surfactant production were identified. Among these, four apolipoprotein genes involved in lipid metabolism and transport were identified and we showed these genes were co-modulated with 17bHSD-2 and -5 in the developing lung. Two days prior the surge of the surfactant synthesis, we showed that mouse fetal lung expresses all the genes involved in adrenal GC synthesis, that this pathway is responsive to CRH and, that GC receptor is translocated to nucleus in response to GC synthesis. Extending out of this critical period, fetal lung produces GC but under the form of deoxycorticosterone (DOC). Our data indicated that DOC and its 5alpha-reduced product the 5DHDOC are key plyaers in the maturation process. Using a multidisciplinary research, we concluded a systematic analysis of the Canadian Neonatal Network (CNN) databases on prematurity and re-confirmed in post-surfactant era that Canadian premature boys continue to be at higher risk of new bronchopulmonary dysplasia compared to that of premature girls. Coexistence of physiopathologic effects of androgens on fetal lung is novel and should now be considered to approach neonatal lung complications. Together, we showed novel role played by the steroids and we have demonstrated novel cross-talk between androgens, corticoids and lipids during the maturation process of the fetal lung. Biomedical data and promising clinical aspects of my work are interconnected.

 

Laboratory members:

Name

Position

Email Address

Dr Pierre Provost

Directeur adjoint

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Eric Boucher

Etudiant PhD

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Wafae Bouhaddioui

Etudiante PhD

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Magaly Kaczmarczyk

Etudiante PhD

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List of publications (2004-2011)

Provost PR, Simard M, Tremblay Y (2004): A link between lung androgen metabolism and the emergence of mature epithelial type II cells. Am. J. Respir. Crit. Care Med. 170: 296-305

Provost, PR and Tremblay Y (2005): Genes Involved in the Adrenal Pathway of Glucocorticoid Synthesis are Transiently Expressed in the Developing Lung. Endocrinology 146:2239-2245

Tremblay, Y and Provost PR, (2006): 17b-HSD 5 gene expression and the emergence of differentiated epithelial Type II cells in fetal lung: A novel role for androgen during the surge of surfactant. Mol Cell Endocrinol 248:118-125 (invited paper)

Simard M, Provost PR and Tremblay Y (2006) Sexually dimorphic gene expression that overlaps maturation of type II pneumonocytes in fetal mouse lungs. Reprod. Biol. & Endocrinol, 4:25(on-line at www.rbej.com/content/4/1/25)

Provost PR, and Tremblay Y (2007) Mouse 3a-hydroxysteroid dehydrogenase mRNA : A marker of lung maturity J. Steroid Biochem Molec Biol, 103 61-64

Do Rego JL, Tremblay Y, Luu-The V, Repetto E, Vallarino M, Bélanger A, Pelletier G, Vaudry H, (2007) Immunocytochemical localization and biological activity of the steroidogenic enzyme cytochrome P450 17a-hydroxylase/C17,20 lyase (P450c17) in the frog brain and pituitary. J Neurochemistry 100:251-268

Simard, M., Boucher, E., Provost, P.R. and Tremblay Y. (2007) Minimization of PCR efficiency differences between standards and samples through dilution of PCR amplicons in reverse transcription buffer. Analytical Biochemistry 362:142-144

Drolet, R., Simard M, Plante, J., Laberge, P. and Tremblay Y (2007) Human type 2 17β-hydroxysteroid dehydrogenase mRNA and protein distribution in placental villi at mid and term pregnancy. Reprod Biol & Endocrinol. 2007, 5:30 ;doi:10.1186/1477-7827-5-30

Manjunath S. Shet1, Charles W. Fisher2, Yves Tremblay3, Alain Belanger3, Alan J. Conley4, J. Ian Mason5 and Ronald W. Estabrook (2007) Comparison of the 17a-hydroxylase/C17,20-lyase activities of porcine, guinea pig and bovine P450c17 using purified recombinant fusion proteins containing P450c17 linked to NADPH-P450 reductase Drug Metabolism Reviews, 39: 1–19

Zheng, X, Price, CA, Tremblay, Y, Lussier, JG and Carrière P. (2008) Role of transforming growth factor-b1 in gene expression and activity of oestradiol and progesterone-generating enzymes in FSH-stimulated bovine granulosa cells. Reproduction, 136:247-257

Provost PR, Boucher E, and Tremblay Y (2009) Apolipoprotein A-I, A-II, C-II, and H expression in the developing lung and sex difference in surfactant lipids. J. Endocrinol 200:321-330

Justin C. Churaa, Hyung S. Ryua, Marc Simardb, Donald Poirierb, Yves Tremblayb, Doris C. Brookera, Charles H. Blomquista, Peter A. Argentaa* (2009) Steroid Converting Enzymes in Human Ovarian Carcinomas. Mol Cell Endocrinol 301 vol 1-2:51-58

Boucher, E., Provost PR, Plante J. and Tremblay Y (2009), Regulation of androgen receptor and 17β-hydroxysteroid dehydrogenase type 2 during the sacculo-alveolar transition period in the neonatal mouse lung. Mol Cell Endocrinol, 311:109-119

Plante, J., Simard, M., Rantakari, P., Côté M., Provost, P.R., Poutanen M., Tremblay Y. (2009) Epithelial cells are the major sites of hydroxysteroid (17β) dehydrogenase 2 ans androgen receptor expression in fetal mouse lungs during the period that overlapping the surge of surfactant J Steroid Biochem Molec Biol 117: 139-145

Simard, M., Plante, J., Boucher, M., Provost, P.R., and Tremblay Y (2010) Type 2 and 5 17β-Hydroxysteroid dehydrogenase and androgen receptor in the human fetal lung. Mol Cell Endocrinol 319 79-87

Provost, PR, Lima P, Tremblay Y, and Blomquist CH (2010) A useful cell system for studying the regulation of 17HSD/KSR type 2 activity and expression in ovarian epithelial cancer, J Steroid Biochem & Mol Biol 122:295-301

Boucher, E., Provost, P.R., Devillers, A. and Tremblay, Y. (2010) Levels of Dihydrotestosterone, Testosterone, Androstenedione, and Estradiol in Canalicular, Saccular, and Alveolar mouse Lungs. Lung 188:229-233

Provost, PR and Tremblay Y (2010) Elevated expression of four apolipoproteins genes during the 32-35 week gestation window in the human developing lung. Early Human development 86: 529-534

Seaborn, T., Simard, M., Provost, PR, Piedboeuf, B, and Tremblay Y (2010) Sex Hormone Metabolism in Lung Development and Maturation TRENDS in Endocrinol & Metab, invited review, 21:729-738

Bresson, E., Seaborn, T., Côté, M., Cormier, G., Provost, P.R., Piedboeuf, B, and Tremblay, Y., (2010) Gene expression profil of androgen modulated genes in the murine fetal developing lung. Reprod Biol &Endocrinol, 8:2

Côté, M., Provost, PR, Gérard-Hudon, MC., and Tremblay Y (2010) Apolipoprotein C-II and Lipoprotein Lipase Show a Temporal and Geographic Correlation with Surfactant Lipid Synthesis in Preparation for Birth. Bio Med Central: Developmental Biology, Vol 10, p111

Simard, M., Côté, M., Provost, PR.,Tremblay, Y. (2010) Expression of Genes related to the Hypothalamic-Pituitary-Adrenal-Axis in Murine fetal Lungs in Gestation. Reprod. Biol. & Endocrinol 8:134

Roberge, S., Lacasse, Y., Tapp. S., Tremblay, Y., and Bujold, E. and GRACE Collaborative Groups collaborators: Amorim, MM, Fekih, M., Kari, A., Liu, J., Qublan, HS. (2011) Role of sex in response to antenatal glucocorticoids to prevent respiratory distress syndrome: systematic review and meta-analysis J of Obstet & Gyncol Canada, March 216-226

Côté, M., Provost, PR and Tremblay Y (2011) Apolipoprotein A-I, A-II, and H mRNA and protein accumulation sites in the developing lung in late gestation BMC Research Notes 4:235 doi 10.1186/1756-0500-4-235

Tondreau, MY., Boucher, E. Simard, M. Tremblay, Y. Bilodeau, JF., (2011) Sex-Specific perinatal expression of glutathione peroxidases during mouse lung development. Mol Cell Endocrinol (Submitted)

(2011) Human type 2 17beta-hydroxysteroid dehydrogenase in umbilical vein and artery endothelial cells: Differential inactivation of sex steroids according to the vessel type. Endocrine http://dx.doi10.1007/s12020-011-9519-5

Seaborn, T., Moulin, J.-A., Côté, M and Tremblay Y., (2011) Promoting the “3R’s” Principle in developmental biology with early and convenient diagnosis of pregnancy in mice. J. Reprod and Dev Vol 57,5 (October)

Binet, Marie-Eve, Bujold, E., Lefebvre, F., Tremblay, Y., Piedboeuf, B for CNN (2011) Role of gender in morbidity and mortality of the extremely premature neonates. Am J Perinat DOI: http://dx.doi.org/10.1055/s-0031-1284225

Bousquet, J et al. (2011) Severe chronic allergic (and related) diseases: a uniform approach – a MeDALL-GA2LEN-ARIA Position Paper In collaboration with the WHO Collaborating Center for Asthma and Rhinitis (Submitted) (Collaborative paper as member of Soc Pneumologie Langue Francaise)

 

Books chapters published

L’influence de Mars et de Vénus sur le développement pulmonaire: Implications en recherche biomédicale et au-delà (accepted CIHR-IGH as Casebook) Marc Simard, Eric Boucher, Yves Tremblay

The influence of Mars and Venus on lung development: implications for biomedical research and beyond. Marc Simard, Eric Boucher, Yves Tremblay (accepted CIHR-IGH as Casebook)

 

Books published

Impact de la prématurité et du sexe sur la santé de l’enfant. Une approche transdisciplinaire (2010). Editors Anne-Marie Gagné and Marc Simard under the direction of Dr Yves Tremblay and Raymond Lambert. Saarbrücken: Editions Universitaires Européennes, 113 pages (ISBN 978-613-1-53318-1) Results from interactive work under the direction of DRs Raymond Lambert and Yves tremblay (version électronique : http://www.fmed.u;laval.ca/prema/)

 

Autres publications

Raymond D. Lambert (MSc, DSc, CRCHUL et chercheur honorifique du CRBR), Yves Tremblay (PhD, Ob/Gyn, CRCHUL et CRBR, UL), Bruno Piedboeuf (MD, directeur des départements hospitalier (CHUQ) et universitaire (UL) de pédiatrie, CRCHUL) et Jacques Mailloux (MD, gynécologie-reproduction, CHUL) Mémoire sur le projet de loi 89, la "Loi sur les activités cliniques et de recherche en matière de procréation assistée et modifiant d'autres dispositions législatives", présenté devant la Commission des affaires sociales de 28 mars 2006 (http://www.assnat.qc.ca/fra/37legislature2/commissions/cas/depot-pl89.html)

Tremblay Y (Fall 2010) How I became a fan of Sex Differences. Intersections vol 2 #1 page 4-7 A Newletter of the Institute for Gender and Health Special Issue CIHR-IGH celebrates 10th Anniversary

Tremblay Y (Automne 2010) Comment je suis devenu un partisan des differences entre les sexes Intersections vol 2 #1 page 4-7 Un bulletin de l’Institut de la santé des femmes et des hommes. Numéro spécial CIHR-ISFH fête ses 10 ans.

Lambert, RD, Monnier-Barbarino, P. et Tremblay Y La conduite responsable de la recherche Les cadres normatifs. L’apport de la transdisciplinarité en ligne à l’élaboration d’un cadre réglementaire : Une démonstration de concept. (Chapitre 11) (Cours ETH-7901)

 

Awards :

Directeur du réseau en santé respiratoire (RSR) du FRQ-S 2011- …