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Etude Du Rôle Du Récepteur Nucléaire FXR Dans La Physiologie Et La Physiopathologie Testiculaire

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Etude Du Rôle Du Récepteur Nucléaire FXR Dans La Physiologie Et La Physiopathologie Testiculaire Etude du rôle du récepteur nucléaire FXRα dans la physiologie et la physiopathologie testiculaire Emmanuelle Martinot To cite this version: Emmanuelle Martinot. Etude du rôle du récepteur nucléaire FXRα dans la physiologie et la phys- iopathologie testiculaire. Sciences agricoles. Université Blaise Pascal - Clermont-Ferrand II, 2015. Français. NNT : 2015CLF22644. tel-01374864 HAL Id: tel-01374864 https://tel.archives-ouvertes.fr/tel-01374864 Submitted on 2 Oct 2016 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. UNIVERSITEBLAISEPASCALUNIVERSITED'AUVERGNE N°D.U.:2644Année2015 ECOLEDOCTORALEDESSCIENCESDELAVIE,SANTE, AGRONOMIE,ENVIRONNEMENT N°d'ordre:677 Thèse Présentéeàl'UniversitéBlaisePASCAL Pourl'obtentiondugradede DOCTEURD'UNIVERSITE Spécialité:PhysiologieetGénétiqueMoléculaire (EndocrinologieMoléculaireetCellulaire) Présentéeetsoutenuepubliquement par EmmanuelleMARTINOT le11décembre2015 EtudedurôledurécepteurnucléaireFXRdanslaphysiologieetlaphysiopathologie testiculaire. Président: Pr.PatrickVERNET,EA4645,UniversitéBlaisePascal,ClermontFerrand Rapporteurs: Pr.NathalieRIVES,EA4308,FacultédeMédecineetdePharmacie,Rouen Pr.VirginieROUILLERFABRE,INSERMUMR967,UniversitéParisDiderot Examinateur: Dr.LaurentDUBUQUOY,INSERMU995,Lille Directeurdethèse: Dr.DavidVOLLE,GReD/INSERMU1103/CNRSUMR6293,ClermontFerrand LaboratoireGReDUMRCNRSINSERMClermontUniversité Remerciements JeremerciesincèrementlesprofesseursNathalieRIVESetVirginieROUILLERFABREd'avoiraccepté de considérer mes travaux de thèse en tant que rapporteurs. Je remercie également le docteur LaurentDUBUQUOY,examinateur,pourl'investissementdontilafaitpreuvedansl'évaluationdece travaildethèse.Enfin,merciauprofesseurPatrickVERNETdem'avoirfaitl'honneurdeprésiderce jury.Pourletempsprécieuxquechacundevousapuaccorderàlalectureattentivedecemanuscrit, merci. 1 VRV]%GC1H: 1QJ JV]:` 1VRVHV `:0:%6:`:1 CQG=V R:` 1HCVVJ]`X]:`: 1QJQ%VJHQ%`RV]%GC1H: 1QJ7 ` 1HCV 1CV:H1R1I]:H %`Q$VJ1 :C `:H 01:1$J:C1J$]: .1:71JRV`1H1VJ I1HV8 :` 1JQ 5:] 1:` 5V$:5VRV5Q%:1JVC5:`%5RV<V5QG:HH:`Q5:`QJ5 .-;<QCCV= J]`X]:`:` 1QJ ` 1HCV 1CV:H1RR]: .1:7`V$%C: VI:CVV6%:CI: %`: 1QJ1JI1HV8 :` 1JQ 5:] 1:` 5V$:5VRV5Q%:1JVC5:`QJ5.J=:J-;<CCV= J`X011QJ5JHQ :`$V ` 1HCV RVJ 1`1H: 1QJQ`I%C 1]CV`QCVQ` .VG1CV:H1RJ%HCV:``VHV] Q`1JIQ%V V 18 :` 1JQ 5VRV5:] 1:` 5Q%:1JVC5:`%5RV<5>.;;-IV; QG:HH:`Q5:`QJ5VJQ1 @.QQJ=:J-;<CC= J]`X]:`: 1QJ V:` 1HCV%10:J QJ ]`XVJ XVJ:JJV6V7 JJV6V ]V`I1Q$VJV1 .VH`1 1H:C V]`Q`:J1V`1J$G1QIVR1H:C1%V-^`V01V1_ :] 1:` 5V$:5:` 1JQ 5QCCV= ]V`I: Q$VJV15 JJV6V :`JVQ1R`VHV] Q`:C].:7:IQCVH%C:`C1J@GV 1VVJG1CV:H1R:JR V`Q1R1$J:C1J$-^`V01V1_ :] 1:` 5V$:5:` 1JQ 5:`QJ5QG:HH:`Q5QCCV= VCC%C:`:JRQCVH%C:`1`VH1VJHV5 JJV6V 1CVH1RC V`:CVV` 1C1 7.`Q%$.R`Q V1JRQ%]CVR1CVH1RVHV] Q`1$J:C1J$: .1:7 1J1HV8 :] 1:` 5 V$: 5 :` 1JQ 5 QII1V` 5 Q% VJ 5 :`HV:% @ RV < 5 :`QJ 5 .QJ=:J-5QG:HH:`Q5QCCV= V]: QCQ$75 JJV6V V]: Q Q61H1 7 1JR%HVR G7 JVQJ: :C V6]Q%`V Q R1V .7C 1CGV `QC 1 I:1J :1JVR .`Q%$.Q% :R%C .QQR01: .VJ%HCV:``VHV] Q`8 V$:5:] 1:` 5:` 1JQ 5:`%5:`.QQJ=:J-QCCV= 6]V` ]1J1QJ5 1 VRV]%GC1H: 1QJ JJV6V RVJ 1`1H: 1QJQ` .VC1J@GV 1VVJ .V.7]Q .:C:IQR]1 %1 :`7:61:JR .V V 1H%C:`Q`].:JJ%HCV:` `VHV] Q`1J:R%C I:CVI1HV8 V$:5:` 1JQ 5:] 1:` 5RV<5:`%5:`QJ5;:1`:<5.QQJ=:J-5QG:HH:`Q5 QCCV= JRQH`1JQCQ$75 JJV6V 1CV:H1R:C V`I:CVIQ%V`V` 1C1 71JIV :GQC1H7JR`QIVHQJ V6 8 V$: :` 1JQ 5:] 1:` 5=<5<<5-@5=IQJRQ7:JR;:`QJ5; <= CQJV5 X%IX <V CV`XHV] V%`J%HCX:1`VRV:H1RVG1C1:1`V5II:=Q`1 :1`VIVJ R:JCV`Q1V5C1J V 1J5 CV `V1J V CV $C:JRV %8 1J Y ]Q%` HV RV`J1V` V RV0VJ% H`Q1:J :% HQ%` RV W:JJXV5RV]:` CVTCVHVJ `:C_=Q%VR:JCVHQJ `TVRVC.QIQ :1VR%.QCV X`QC5 RV:H1RVG1C1:1`V5RV `1$7Q%VJHQ`VR%$C%HQ8 C% `XHVIIVJ 5 < :1J1 _ V C1$:JR5 CV :H1RV G1C1:1`V5 QJ X X CQH:C1X R:J CV V 1H%CV5 Q%CV0:J C: _QJ R% TCV ]Q VJ 1VC RV < R:J HV Q`$:JV5 V ]C% I R:J C: `QJH 1QJ RV `V]`QR%H 1QJ I=8 :1 CV X %RV I ; HV %=V `V VJ _; ]`XVJ ]V% JQIG`V%V5 V `QH:C1XV %` QJ 1I]C1H: 1QJ R:J CV HQTV R% IQC1I RV X6V 7 C:H 10: 1QJ1J010Q<]:`%J:$QJ1 V7._VHQJR%1 :.V<;%` V`IV; `X]`V1QJRVC: X`6Q$VW8 {QJTCVR:JCVHQJTCVRVC:H 101 XVJRQH`1JVRVHVCC%CVRV7R1$5C1I]:H RVC:H 10: 1QJ 1J010QRV<%`C:.7QCQ$1V]C%$CQG:CVR% V 1H%CVJ:=I:1X X:GQ`RX;HV=Q8=V VCCV X %RV V`:1VJ ]Q%` :J ]V` 1JVJ V X :J RQJJX _ < V H1GCX ]Q%` CV `:1 VI RV .CQ$1VIX :GQ_ V_7I1VWV8 =HVHQJ V6 V5CQG=VH 1`RVHV `:0:1CRV .WVX :1 RX %R1V`CVTRV<R:JC:.7 C:]..71QCQ$1VR% V 1H%CV5VJ7:J %`7VR%JIQRWI%`1JRQJ CV$WHQR:J <:X X8|Q`X%C : RXIVJ _7_C:]V` VRV<]`XR1]QVCV V 1H%CV;%JV I :C1 X RV HVCC%CV I R:J %J HQJ V6 V ._ RV .QCV :V 6 _ C: %`R :H 10: 1QJRVC:1$J:C1: 1QJ<:%HQ%`RVC:]%GV` XHQJR%1 ;%JRX`:% RVC:R1``X`VJH1: 1QJ I1J:CV5:QH1XV;%JV:C X`: 1QJRVC:`QJH 1QJVJRQH`1JVR% V 1H%CV6_Q% `VC:`X$%C: 1QJRV C: X`Q6RQ$VJWVR:JCVHVCC%CVRVV7R1$5<]:` 1H1]V:%HQJ `TCVRV`QJH 1QJV` QC1VJJVV RVC:]`QC1`X`: 1QJVLQ%R1``X`VJH1: 1QJRVHVCC%CV$VI1J:CVQ%.8 VJVIGCVRVHVRQJJXVRX`1J1VJ <HQII%JJQ%0VC:H V%`1I_R:JCVHQJTCVRVC: .7Q$1V V 1H%C:1`V V RV0`:1VJ YV ]`1V VJ HQJ1RX`: 1QJ _; C% 1C1: 1QJ RV ICXH%CV :$QJ1 VV LQ%:J :$QJ1 VRV<VH:R`VR% `:1 VI.QCQ$1VI_8 Q HCX7< V 1H%CV5 X`6WV5:]Q] QVV R1``X`VJH1: 1QJ$V`IV5HVCC%CV$V`I1J:CV Q.8 G `:H <1 .G1CV:H1RJ%HCV:``VHV] Q`5]I1J:J C7V6]`VVR1JC10V`51J V 1JV5@7:JR:R`VJ:C 8`VHVJ 71J V`V 1J<.GVVJ1JH`V:1J$R%V Q1 HVJ `:C`QCV1J.HQJ `QCQ` . 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