Placental antiangiogenic prolactin fragments are increased in human and rat maternal diabetes

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1842

Article

Perimenis, P.^1,6,7  Bouckenooghe, T.¹  Delplanque, J.^2,7  Moitrot, E.¹  Eury, E.^2,7  Lobbens, S.^2,7  Gosset, P.³  Devisme, L.⁴  Duvillie, B.⁵  Abderrahmani, A.^2,7  Storme, L.¹  Fontaine, P.^1,7,8  Froguel, P.^2,7,8  Vambergue, A.^1,7,8 

[1] Univ Lille 2, EA 4489, F-59045 Lille, France

[2] Univ Lille 2, CNRS UMR8199, F-59000 Lille, France

[3] Catholic Inst Lille GHICL, Hosp Grp, Anatomopathol Dept, F-59160 Lomme Les Lille, France

[4] CHRU Lille, Univ Hosp, Anatomopathol Dept, F-59037 Lille, France

[5] INSERM U845, Res Ctr Growth & Signaling, F-75014 Paris, France

[6] Catholic Inst Lille GHICL, Hosp Grp, Dept Diabetol, F-59160 Lomme Les Lille, France

[7] European Genom Inst Diabet, F-59000 Lille, France

[8] CHRU Lille, Univ Hosp, Claude Huriez Hosp, Dept Diabetol, F-59037 Lille, France

关键词: Diabetes;    Decidual prolactin-related protein;    Pregnancy;    Prolactin;    Vasoinhibin;   

DOI  :  10.1016/j.bbadis.2014.06.026

来源: Elsevier

【 摘 要 】

Introduction/objectives: 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. (C) 2014 Elsevier B.V. All rights reserved.

【 授权许可】

Free