Perimenis P, Bouckenooghe T, Delplanque J, Moitrot E, Eury E, Lobbens S, Gosset P, Devisme L, Duvillie B, Abderrahmani A, Storme L, Fontaine P, Froguel P, Vambergue A
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.
EA 4489, Perinatal environment and Growth, University of Lille 2, 1 place de Verdun, 59045 Lille, France.
Biochim Biophys Acta. 2014 Sep;1842(9):1783-93. doi: 10.1016/j.bbadis.2014.06.026. Epub 2014 Jun 28.
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.
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.
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.
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.
引言/目的：胎盘在糖尿病母亲体内对胎儿发育和编程的作用尚不清楚。蜕膜子宫内膜细胞产生的催乳素（PRL）可能会产生影响。虽然全长PRL具有促血管生成作用，但骨形态发生蛋白-1（BMP-1）和/或组织蛋白酶D（CTSD）加工后的形式具有抗血管生成作用。目的是研究蜕膜PRL及其抗血管生成片段在1型糖尿病女性（T1D）和后代体重低于对照组的妊娠糖尿病大鼠胎盘组织中的作用。
在分娩时评估T1D胎盘组织（n = 8）中的PRL、BMP-1和CTSD基因表达以及PRL蛋白水平，并与对照组（n = 5）进行比较。Wistar大鼠在妊娠第7天接受链脲佐菌素（STZ）（n = 5）或烟酰胺（NCT）加STZ（n = 9）或赋形剂（n = 9）。在出生时进行胎盘全基因组基因表达和PRL免疫印迹分析。
在人胎盘中，T1D组的PRL（p<0.05）和BMP-1（p<0.01）基因表达增加，且裂解型PRL的量高于对照组（p<0.05）。在大鼠中，STZ组的糖尿病比NCT-STZ组更明显，伴有子宫内生长受限。两个糖尿病组的蜕膜催乳素相关蛋白（Dprp）（p<0.01）和Bmp-1（p<0.001）基因均上调，与对照组相比，STZ组（p<0.05）和NCT-STZ组（p<0.05）的裂解型PRL量增加。在大鼠或女性中未观察到CTSD基因表达的差异。
PRL家族水平的改变与大鼠和T1D女性的母体糖尿病有关，提示这些激素的胎盘变化会影响胎儿发育。
