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MAFortier

Michel A. Fortier, Ph.D.

Professor

Université Laval

Département d'obstétrique et gynécologie

Centre de recherche en biologie de la reproduction

Centre de recherche du CHUL-CHUQ

Unité d'ontogénie-reproduction, Local T3-67

2705, boul. Laurier

Québec (Québec) G1V 4G2

Phone: (418) 656-4141, poste 46141

Fax: (418) 654-2783

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Research Interest:

  • Reproductive endocrinology
  • Maternal recognition of pregnancy
  • Contribution of prostaglandins in the etiology of menstrual disorders
  • Molecular and celluar mechanisms involved in the regulation of prostaglandin biosynthesis.

 

Recent results:

Prostaglandins and regulation of female reproductive function.

My research program is to study the contribution of prostaglandins (PGs) to the regulation of female reproductive function and embryo-maternal interactions leading to recognition of pregnancy. In this context, we aim at providing an integrated view of the complementary mechanisms regulating the production and action of specific PG responses in the uterus. The working hypothesis is that PGs are the final integrating system in the regulation of female reproductive function and recognition of pregnancy. A major contribution of my laboratory has been to develop cell culture models to demonstrate the leading role played by PGs in embryo-maternal interactions leading to recognition and establishment of pregnancy in the cow and regulation of menstruation in women. Two major discoveries from our laboratory are having major impacts on the understanding of the contribution of PGs to reproductive function and other body systems[1]. First, we have discovered that the enzyme responsible for PGF2α production in the endometrium is a new prostaglandin F-synthase (PGFS) with aldose reductase activity. This has opened a entirely new field of research whereby aldose reductases may mediate physiologic and pathologic processes through their PGFS activity. Second, we have been the first to demonstrate functional regulation in the female reproductive system, of a newly identified PG transporter, showing that the transport of PGs across cell membranes is another site of regulation of PG action in physiological processes. Globally our results support the concept of primary involvement of prostaglandins in reproductive function in general and at the time of establishment of pregnancy in particular.

 

Lab Members: 

Name

Position

Email Address

Pierre Chapdelaine

Professionnel de recherche

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Eva Bresson

Assistante de recherche

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Nicolas Lacroix-Pépin

Etudiant PhD

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List of Publications:

  1. Bresson E, Boucher-Kovalik S, Chapdelaine P, Madore E, Harvey N, Laberge PY, Leboeuf M & Fortier MA (2010). The human aldose reductase AKR1B1 qualifies as the primary prostaglandin F synthase in the endometrium. 96 (1): 210-219. CIHR.  
  2. Madore É, Harvey N, Parent J, Chapdelaine P, Arosh JA & Fortier MA (2003)
    An aldose reductase with 20αHSD activity is most likely the enzyme responsible for the production of PGF2a in the bovine endometrium. J Biol Chem, 278:11205-11212. NSERC-CIHR 

These seminal publications demonstrates unequivocally that AKR1B1 is a highly functional PGF synthase and that its PGFS activity can be blocked in the human endometrium by aldose reductase inhibitors developed for the polyol pathway.

 

  1. Kang J, Chapdelaine P, Laberge PY & Fortier MA (2006) Functional characterization of prostaglandin transporter and terminal prostaglandin synthases during decidualization of human endometrial stromal cells. Hum Reprod. 21 (3):592-9. CIHR.
  2. Kang J, Chapdelaine P, Parent J, Madore E, Laberge PY & Fortier MA (2005)
    Expression of human prostaglandin transporter in the human endometrium across the menstrual cycle. J Clin Endocrinol Metab, 90 (4):2308-2313 Apr. CIHR

These publications present the expression and functional involvement of the influx transporter PGT also known as SLCOA1 in the transit of prostaglandins in human endometrium and cultured endometrial cells. In the present proposal we will extend these studies with the efflux transporter MRP4 or ABCC4 and evaluate their contribution to the net production of PGE2 and PGF2α.

 

  1. Chapdelaine P, Kang J, Boucher-Kovalik S, Caron N, Tremblay JP & Fortier MA (2006) Decidualization and maintenance of a functional prostaglandin system in human endometrial cell lines following transformation with SV40 large T antigen. Mol Hum Reprod. 12(5):309-19. CIHR 

This study describes the generation and characterization of normal endometrial epithelial and stromal cell lines that will be used extensively in the present project.

 

Published refereed papers (student under my supervision are indicated in bold)

  1. Phillips RJ, Al-Zamil H, Hunt LP, Fortier MA & Lopez Bernal A (2010). Genes for prostaglandin synthesis, transport and inactivation are differentially expressed in human uterine tissues, and the prostaglandin F synthase AKR1B1 is induced in myometrial cells by inflammatory cytokines. Mol Hum Reprod, 17 (1) 1-13. CIHR
  2. Bresson E, Boucher-Kovalik S, Chapdelaine P, Madore E, Harvey N, Laberge PY, Leboeuf M & Fortier MA (2011). The human aldose reductase AKR1B1 qualifies as the primary prostaglandin F synthase in the endometrium. J Clin Endocrin Metab, 96 (1) 210-219. CIHR.
  3. Gauvreau D, Moisan V, Roy M, Fortier MA & Bilodeau JF (2010). Expression of prostaglandin E synthases in the bovine oviduct. Theriogenology, 73(1):103-11. NSERC.
  4. Breuiller-Fouché M, Leroy MJ, Dubois O, Reinaud P, Chissey A, Qi H, Germain G, Fortier MA & Charpigny G (2010). Differential Expression of the Enzymatic System Controlling Synthesis, Metabolism, and Transport of PGF2 Alpha in Human Fetal Membranes. Biol Reprod, 83(1):155-62. INRA.
  5. Fortier MA, Krishnaswamy N, Danyod G, Boucher-Kovalik S, Chapdelaine P & Arosh JA (2009). A postgenomic integratred view of prostaglandins in reproduction: implications for other body systems. J Physiol Pharmacol 59(S1):65-89. NSERC
  6. Chapdelaine P, J Kang, S Boucher-Kovalik, N Caron, JP Tremblay & MA Fortier (2006). Decidualization and maintenance of a functional prostaglandin system in human endometrial cell lines following transformation with SV40 large T antigen. Mol Hum Reprod. 12(5):309-19. CIHR
  7. Kang J, P Chapdelaine, PY Laberge & MA Fortier (2006). Functional characterization of prostaglandin transporter and terminal prostaglandin synthases during decidualization of human endometrial stromal cells. Hum Reprod. 21(3):592-9. CIHR
  8. Parent M, E Madore, LA MacLaren & MA Fortier (2006). 15-hydroxyprostaglandin dehydrogenase in the bovine endometrium during the oestrous cycle and early pregnancy. Reproduction. 131(3):573-82. NSERC
  9. Schuler G, U Teichmann, MP Kowalewski, B Hoffmann, MA Fortier, E Madore & K Klisch (2006). Expression of cyclooxygenase-II (COX-II) and 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD)/prostaglandin F-synthase (PGFS) in bovine placentomes: implications for the initiation of parturition in cattle. Placenta. 27(9-10):1022-9. NSERC
  10. Parent J, P Chapdelaine & MA Fortier (2005). Molecular cloning and tissue distribution of microsomal-1 and cytosolic prostaglandin E synthases in macaque. Prostaglandins Other Lipid Mediat, 78(1-4):27-37. CIHR
  11. Parent J & MA Fortier (2005) Expression and contribution of three different isoforms of prostaglandin E synthase in the bovine endometrium. Biol Reprod, 73(1):36-44. NSERC
  12. Kang J, P Chapdelaine, J Parent, E Madore, PY Laberge & MA Fortier (2005). Expression of human prostaglandin transporter in the human endometrium across the menstrual cycle. J Clin Endocrinol Metab, 90(4):2308-2313. CIHR
  13. Banu SK, JA Arosh, P Chapdelaine & MA Fortier (2005). Expression of prostaglandin transporter in the bovine uterus and fetal membranes during pregnancy. Biol Reprod. 73(2):230-236. NSERC

 

Presentations as guest speaker

  1. Fortier MA (2011). Prostaglandine F synthase bovine: Implications dans la santé humaine. Classe des neiges du CRBR, 26-27 mai, Forêt Montmorency.
  2. Fortier MA (2009). Les rôles des prostaglandines dans le système reproducteur féminin. Congrès annuel - Ass. des obstétriciens et gynécologues du Québec, Jonquières, QC, Canada, 14-17 mai.
  3. Fortier MA (2009). Une vision intégrée du rôle des prostaglandines dans l’utérus : un modèle pour comprendre l’ischémie cardiaque et l’échec du Vioxx! Congrès de l’Acfas, Ottawa, ON, May 11.
  4. Fortier MA (2008). A postgenomic integratred view of prostaglandins in reproduction: implications for other body systems. Congress of the Polish Physiological Society, Lublin, Poland, Sept. 11-13.
  5. Fortier MA (2006). L’expression différentielle des prostaglandines dans les différents compartiments utérins au moment de la parturition. INSERM, Paris, France, June 6.
  6. Fortier MA (2005). Biosynthèse, transport et signalisation cellulaire, une vision intégrée de la régulation de la fonction reproductive par les prostaglandines. INSERM, Paris, France, Sept. 27.
  7. Fortier MA (2005). Une vision intégrée du rôle des prostaglandines au moment de la reconnaissance et de l’établissement de la gestation. INRA - Journées RIVAGE 2005, Jouy-en-Josas, France, Juin 06.

 

Communications (student under my supervision are indicated in bold)

  1. Lacroix-Pépin N, Danyod G, Krishnaswamy N, Rong, P, Chapdelaine, P & Fortier, MA (2011). Expression et régulation de MRP4 (Multidrug Resistant associated Protein 4): Nouveau candidat dans la régulation des prostaglandines à l'intérieur de l'endomètre bovin. Journée de la Recherche de la Faculté de médecine de l'Université Laval, Québec, QC, Canada, June 7.
  2. Michaud A, Noel S, Paris G, Luu-The V, Fortier MA & Tchernof A (2011). Adipose Tissue Expression of Genes Coding for Prostaglandin Synthesis Enzymes and Receptors in Women. 93rd annual meeting Endocrine Society, Boston, MA, USA, June 5.
  3. Bresson E, Boucher-Kovalik S, Chapdelaine P, Madore E, Harvey N, Laberge PY, Leboeuf M & Fortier, MA (2010). The human aldose reductase AKR1B1 qualifies as the primary prostaglandin F synthase in the endometrium. 3e symposium annuel du Réseau Québécois en Reproduction, Québec, QC, Canada, 16-17 nov.
  4. Lacroix-Pépin N, Danyod G, Krishnaswamy N, Mondal S, Rong P, Chapdelaine P & Fortier MA (2010). Expression et régulation de MRP4: nouveau candidat dans la régulation des prostaglandines à l'intérieur de l'endomètre bovin. 3e symposium annuel du Réseau Québécois en Reproduction, Québec, QC, Canada, 16-17 nov.
  5. Michaud A, Veilleux A, Caron-Jobin M, Noel S, Mailloux J, Fortier MA & Tchernof A (2010). Expression des gènes de synthèse des prostaglandines dans le tissu adipeux chez la femme. 11e   réunion annuelle de la Société québécois de lipidologie, nutrition, et métabolisme Québec, QC, Canada, 29 avril - 1er mai.
  6. Lacroix-Pépin N, Chapdelaine P & Fortier MA (2010). Relation entre prostaglandines et interleukines dans les cellules endométriales bovines. 12e journée annuelle de la Faculté de médecine de l'Université Laval, Québec, QC, 27 mai.
  7. Beauchemin D, Fortier MA & Bilodeau JF (2009). Régulation différentielle des enzymes de synthèse des prostaglandines et de leur récepteur dans le placenta en prééclampsie. 17e Rencontre Hivernale des Biologistes en Reproduction du Québec, Forêt Montmorency, QC, 26-27 mars.
  8. Chapdelaine P, Harvey N, Mercier G, Bilodeau JF & Fortier MA (2009). La mesure des prostaglandines par LC/MS/MS : un outil en développement pour démontrer l’implication des prostaglandines dans les désordres menstruels et métaboliques. 17e Rencontre Hivernale des Biologistes en Reproduction du Québec, Forêt Montmorency, QC, 26-27 mars.
  9. Beauchemin D, Fortier MA & Bilodeau JF (2009). Régulation différentielle des enzymes de la voie des prostaglandines à effets vasoactif et du récepteur aux thromboxanes dans le placenta en prééclampsie. 10e congrès de la Société québécoise de lipidologie, de nutrition et de métabolisme (SQLNM), Québec, QC, Canada, 30 avril - 2 mai.
  10. Beauchemin D, Fortier MA & Bilodeau JF (2009). Régulation différentielle des prostaglandines et de leurs récepteurs dans le placenta en prééclampsie. 11e journée annuelle de la recherche de la Faculté de médecine de l’Université Laval, Québec, QC, Canada, 2 juin.
  11. Krishnaswamy N, Danyod G, Chapdelaine P & Fortier MA (2009). Involvement of the ERK1/2 pathway during oxytocin-induced PGF2alpha production in the bovine endometrial epithelial cell line bEEL. Society for the Study of Reproduction/Annual Meeting, Pittsburgh, PA, 18-22 juil.  
  12. Mondal S, Danyod G, Krishnaswamy N, Chapdelaine P & Fortier MA (2009). Oxytocin and interferon-Tau regulation of prostaglandin transporter (PGT) and multidrug resistant associated protein 4 (MRP4) in the bovine endometrium. Society for the Study of Reproduction/Annual Meeting, Pittsburgh, PA, 18-22 juil.
  13. Beauchemin D, Roland L, Fortier MA & Bilodeau JF (2009). Étude des enzymes de la biosynthèse de la thromboxane A2 et de la prostacycline ainsi que de leurs récepteurs dans le placenta en prééclampsie. 51e réunion annuelle du Club de Recherche Cliniques du Québec (CRCQ), Lac Delage, QC, Canada, 24-26 sept.  
  14. Beauchemin D, Roland L, Fortier MA & Bilodeau JF (2009). Placental expression of receptors and biosynthesis enzymes for prostacyclin and thromboxane in preeclampsia. 2e Symposium annuel du Réseau Québécois en reproduction (RQR), Montréal, Canada, 17-18 nov.  
  15. Bresson E, Chapdelaine P & Fortier MA (2009). De l'endomètre aux désordres métaboliques: l'activité PGF synthase de l'aldose réductase humaine (AKR1B1), une cible inattendue. 2e Symposium annuel du Réseau Québécois en reproduction (RQR), Montréal, Canada., 17-18 nov.  
  16. Krishnaswamy N, Danyod G, Chapdelaine P & Fortier MA (2009). Involvement of the ERK1/2 pathway during oxytocin induced PGF2a production in the bovine endometrial epithelial cell line bEEL. 2e Symposium annuel du Réseau Québécois en reproduction (RQR), Montréal, Canada, 17-18 nov.  
  17. Lacroix-Pépin N & Fortier MA (2009). Polarité de la production des prostaglandines PGE2 et PGF2a par les cellules épithéliales endométriales bovines en relation avec l'implantation embryonnaire. 2e Symposium annuel du Réseau Québécois en reproduction (RQR), Montréal, Canada, 17-18 nov.  
  18. Mondal S, Danyod G, Krishnaswamy N, Chapdelaine P & Fortier MA (2009). Oxytocin and interferon-tau regulation of prostaglandine transporter (PGT) and multidrug resistant associated protein 4 (MRP4) in the bovine endometrium. 2e Symposium annuel du Réseau Québécois en reproduction (RQR), Montréal, Canada, 17-18 nov.  
  19. Fortier MA, P Chapdelaine, E Zakrzewska, E Madore (2008). The PGFS activity of AKR1B1 as a marker and a new target for management of human pathologies. IXth World Conference on Clinical Pharmacology and Therapeutics. Quebec, QC, July 27-Aug 1.
  20. Chapdelaine P, Danyod G, Fortier MA (2008). Rencontre Hivernale des Biologistes en Reproduction du Québec Forêt Montmorency. March 9-10.
  21. Drolet R, Laberge P, Daris M, Fortier M, Tchernof A. (2007). Adiponectin release is reduced to a larger extent in omental than in subcutaneous adipocytes of obese women. 32nd Canadian Lipoprotein Conference, Beaupré, QC, Canada, October 11-14.
  22. Laflamme J, Chapdelaine P, Fortier MA, Sullivan R (2007). Immortalisation of bovine caput epididymal cells. ASA Annual Meeting, Tampa, Florida, USA, April 18-24.
  23. Fortier MA (2006). Modèles et méthodes pour caractériser les voies de synthèse des prostaglandines dans l'endomètre humain. Rencontre Hivernale des Biologistes en Reproduction du Québec, Forêt Montmorency, QC, Canada, March 12-14.
  24. Chapdelaine P, S Boucher-Kovalik, N Krishnaswamy & MA Fortier (2005). Induction of prostaglandins F2a and E2 production by IL-1B in human endometrial cells may be associated with oxidative stress. Regroupement de Recherche en Reproduction/Réunion Annuelle, Trois-Rivières, QC, Canada, 21 nov.
  25. Gauvreau D, MA Fortier & JF Bilodeau (2005). Étude de l'expression de la cyclooxygénase-1 (COX-1) dans l'oviducte bovin au cours du cycle oestral. Regroupement de Recherche en Reproduction/Réunion Annuelle, Trois-Rivières, QC, Canada, 21 nov.
  26. Zakrzewska E, E Madore, P Chapdelaine & MA Fortier (2005). Messenger spanning siRNA effectively reduces prostaglandins production in human endometrial cells. Regroupement de Recherche en Reproduction/Réunion Annuelle, Trois-Rivières, QC, Canada, Nov. 21.
  27. Zakrzewska E, E Madore, P Chapdelaine & MA Fortier (2005). Downregulation of AKRIB1 and MPGES1 by RNA silencing reduces prostaglandin production in human endometrial cells. SSR Annual Meeting, Québec, QC, Canada, July 24-27.
  28. Zakzewska E, E Madore, P Chapdelaine & MA Fortier (2005). AKR1-B1 et mPGES-1 dans la production des prostaglandines. Rencontre Hivernale des Biologistes en Reproduction du Québec, Forêt Montmorency, QC, Canada, March 6-8.
  29. Kang J, P Chapdelaine & MA Fortier (2005). Functional localization of human prostaglandin transporter in the nucleus of human endometrial cells. SSR annual meeting, Québec, QC, Canada, July 24-27.
  30. Fortier MA, J Kang & P Chapdelaine (2005). Functional characterization of prostaglandin transporter during decidualization of human endometrial stromal cells. SSR annual meeting, Québec, QC, Canada, July 24-27.
  31. Chapdelaine P & MA Fortier (2005). Long promoter and transcriptional regulation of prostaglandin F and E synthases by IL1B in human endometrial cells. SSR annual meeting, Québec, QC, Canada, July 24-27.
  32. Chapdelaine P & MA Fortier (2005). Construction de longs promoteurs et régulation transcriptionnelle par IL-1beta des synthases terminales des prostaglandines F2alpha (PGF synthase) et E2 (mPGES-1) étudiées dans les cellules épithéliales et stromales de l'endomètre humain. Rencontre Hivernale des Biologistes en Reproduction du Québec, Forêt Montmorency, QC, Canada, March 6-8

 

Committee membership

  • Invited Member: CIHR - Clinical Investigation A, December 2010
  • Chair: Science Foundation of Ireland, SRC program, Reproductive Biology Research, Cluster site visit June 2010
  • Chair: CIHR - GSH RFA on Men’s health 2007and 2009

 

Academic responsibilities

Chair: Research space and resources allocation committee CHUQ Research Center, Université Laval 2007 -

 

External reviewer for granting agencies

CIHR, NSERC, Heritage Foundation

 

External reviewer for peer review journal (number of articles reviewed)

  • Member: Faculty of 1000 Diabetes and Endocrinology 2 reviews ranked among top 10% most viewed evaluations in 2011
  • Endocrinology (5), JCEM (4), Biol Reprod (4), Human Reprod (5), Mol Human Reprod (4), Reprod Biol Endocrinol (6) for an average of 30 reviews each year.

 

 

Fortier MA, Chapdelaine P, Bresson E, Madore E.

Applicant: Université Laval

International Application.

Methods for the regulation of the prostaglandin f synthase (pgfs) activity of akr1b1 and uses thereof.

Filed Nov. 2008

No. PCT/CA2008/002012

 

This patent stems from the discovery of an unexpected PGFS activity of the human and bovine aldose reductases. AKR1B1 is known to contribute to cardiovascular, neurological and kidney complications secondary to diabetes. The discovery that the same enzyme could generate the bioactive lipid mediator PGF2α a potent vasoconstrictor involved in ischemic responses opens entirely new avenues for diagnosis and treatment of those lethal and highly prevalent pathologies.