title: Placental antiangiogenic prolactin fragments are increased in human and rat maternal diabetes.
abstract: OBJECTIVE
  The role of the placenta in diabetic mothers on fetal development and programming is unknown. Prolactin (PRL) produced by decidual endometrial cells may have an impact. Although full-length PRL is angiogenic, the processed form by bone morphogenetic protein-1 (BMP-1) and/or cathepsin D (CTSD) is antiangiogenic. The objectives were to investigate the involvement of decidual PRL and its antiangiogenic fragments in placentas from type-1 diabetic women (T1D) and from pregnant diabetic rats with lower offspring weights than controls.
  
  
  METHODS
  PRL, BMP-1, and CTSD gene expressions and PRL protein level were assessed in T1D placentas (n=8) at delivery and compared to controls (n=5). Wistar rats received, at day 7 of pregnancy, streptozotocin (STZ) (n=5) or nicotinamide (NCT) plus STZ (n=9) or vehicle (n=9). Placental whole-genome gene expression and PRL western blots were performed at birth.
  
  
  RESULTS
  In human placentas, PRL (p<0.05) and BMP-1 (p<0.01) gene expressions were increased with a higher amount of cleaved PRL (p<0.05) in T1D than controls. In rats, diabetes was more pronounced in STZ than in NCT-STZ group with intra-uterine growth restriction. Decidual prolactin-related protein (Dprp) (p<0.01) and Bmp-1 (p<0.001) genes were up-regulated in both diabetic groups, with an increased cleaved PRL amount in the STZ (p<0.05) and NCT-STZ (p<0.05) groups compared to controls. No difference in CTSD gene expression was observed in rats or women.
  
  
  CONCLUSIONS
  Alterations in the levels of the PRL family are associated with maternal diabetes in both rats and T1D women suggesting that placental changes in these hormones impact on fetal development.
authors.affiliation: EA 4489, Perinatal environment and Growth, University of Lille 2, 1 place de Verdun, 59045 Lille, France; Department of Diabetology, Hospital Group of Catholic Institute of Lille (GHICL), 115 rue du grand but, 59160 Lomme, France; European Genomic Institute for Diabetes (EGID), FR 3508, 59000 Lille, France. Electronic address: perimenis@voila.fr.
authors.forename: P
authors.initials: P
authors.lastname: Perimenis
authors.affiliation: EA 4489, Perinatal environment and Growth, University of Lille 2, 1 place de Verdun, 59045 Lille, France. Electronic address: thomas.bouckenooghe@gmail.com.
authors.forename: T
authors.initials: T
authors.lastname: Bouckenooghe
authors.affiliation: CNRS-UMR8199, Lille 2 University, 1 rue du professeur Calmette, 59000 Lille, France; European Genomic Institute for Diabetes (EGID), FR 3508, 59000 Lille, France. Electronic address: jerome@good.ibl.fr.
authors.forename: J
authors.initials: J
authors.lastname: Delplanque
authors.affiliation: EA 4489, Perinatal environment and Growth, University of Lille 2, 1 place de Verdun, 59045 Lille, France. Electronic address: emma_moitrot@hotmail.com.
authors.forename: E
authors.initials: E
authors.lastname: Moitrot
authors.affiliation: CNRS-UMR8199, Lille 2 University, 1 rue du professeur Calmette, 59000 Lille, France; European Genomic Institute for Diabetes (EGID), FR 3508, 59000 Lille, France. Electronic address: elodie.eury-wattez@outlook.fr.
authors.forename: E
authors.initials: E
authors.lastname: Eury
authors.affiliation: CNRS-UMR8199, Lille 2 University, 1 rue du professeur Calmette, 59000 Lille, France; European Genomic Institute for Diabetes (EGID), FR 3508, 59000 Lille, France. Electronic address: stephane.lobbens@good.ibl.fr.
authors.forename: S
authors.initials: S
authors.lastname: Lobbens
authors.affiliation: Anatomopathological Department, Hospital Group of Catholic Institute of Lille (GHICL), 115 rue du grand but, 59160 Lomme, France. Electronic address: gosset.pierre@ghicl.net.
authors.forename: P
authors.initials: P
authors.lastname: Gosset
authors.affiliation: Anatomopathological Department, CHRU Lille, University Hospital, 59037 Lille, France. Electronic address: louise.devisme@chru-lille.fr.
authors.forename: L
authors.initials: L
authors.lastname: Devisme
authors.affiliation: INSERM U845, Research Center Growth and Signaling, 96 rue didot, 75014 Paris, France. Electronic address: bertrand.duvillie@inserm.fr.
authors.forename: B
authors.initials: B
authors.lastname: Duvillie
authors.affiliation: CNRS-UMR8199, Lille 2 University, 1 rue du professeur Calmette, 59000 Lille, France; European Genomic Institute for Diabetes (EGID), FR 3508, 59000 Lille, France. Electronic address: amar.abderrahmani@univ-lille2.fr.
authors.forename: A
authors.initials: A
authors.lastname: Abderrahmani
authors.affiliation: EA 4489, Perinatal environment and Growth, University of Lille 2, 1 place de Verdun, 59045 Lille, France. Electronic address: laurent.storme@chru-lille.fr.
authors.forename: L
authors.initials: L
authors.lastname: Storme
authors.affiliation: EA 4489, Perinatal environment and Growth, University of Lille 2, 1 place de Verdun, 59045 Lille, France; European Genomic Institute for Diabetes (EGID), FR 3508, 59000 Lille, France; Department of Diabetology, CHRU Lille, University Hospital, Claude Huriez Hospital, rue Polonovski, 59037 Lille, France. Electronic address: pierre.fontaine@chru-lille.fr.
authors.forename: P
authors.initials: P
authors.lastname: Fontaine
authors.affiliation: CNRS-UMR8199, Lille 2 University, 1 rue du professeur Calmette, 59000 Lille, France; European Genomic Institute for Diabetes (EGID), FR 3508, 59000 Lille, France; Department of Diabetology, CHRU Lille, University Hospital, Claude Huriez Hospital, rue Polonovski, 59037 Lille, France. Electronic address: p.froguel@imperial.ac.uk.
authors.forename: P
authors.initials: P
authors.lastname: Froguel
authors.affiliation: EA 4489, Perinatal environment and Growth, University of Lille 2, 1 place de Verdun, 59045 Lille, France; European Genomic Institute for Diabetes (EGID), FR 3508, 59000 Lille, France; Department of Diabetology, CHRU Lille, University Hospital, Claude Huriez Hospital, rue Polonovski, 59037 Lille, France. Electronic address: anne.vambergue@chru-lille.fr.
authors.forename: A
authors.initials: A
authors.lastname: Vambergue
mesh_terms: D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D055395:Bone Morphogenetic Protein 1 / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D047109:Fetal Development; D006801:Humans; D007124:Immunoenzyme Techniques; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011388:Prolactin / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D011388:Prolactin; C525705:BMP1 protein, human; C525708:Bmp1 protein, rat; D055395:Bone Morphogenetic Protein 1
keywords: Decidual prolactin-related protein; Diabetes; Pregnancy; Prolactin; Vasoinhibin