Capobianco Evangelina, Fornes Daiana, Linenberg Ivana, Powell Theresa L, Jansson Thomas, Jawerbaum Alicia
Laboratory of Reproduction and Metabolism, CEFYBO. CONICET School of Medicine, University of Buenos Aires, Argentina.
Section of Neonatology, Department of Pediatrics Department of OB/GYN, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045, USA; Division of Reproductive Sciences, Department of OB/GYN, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045, USA.
Mol Cell Endocrinol. 2016 Feb 15;422:221-232. doi: 10.1016/j.mce.2015.12.020. Epub 2015 Dec 30.
A family history of diabetes predisposes to gestational diabetes mellitus (GDM). We hypothesized that female offspring of rats with pre-gestational diabetes will develop GDM, a pathology associated with fetal overgrowth and altered placental signaling. We found normal glycemia and insulinemia in the offspring from pre-gestational diabetic rats at three months of age. However, consistent with GDM, maternal hyperglycemia and hyperinsulinemia and increased fetal weight were evident when compared to controls. In this intrauterine programmed GDM model, the placentas showed alterations in mTOR pathway: unchanged phosphorylation of 4EBP-1 and PKCα despite reduced total expression of 4EBP-1 and PKCα, and increased phosphorylation of SGK1. GDM placentas also showed reduced expression of PPARα and PPARγ, and increased lipoperoxidation, nitric oxide production and peroxynitrite-induced damage. We conclude that exposure of maternal diabetes in utero programs GDM in the female offspring, leading to a GDM model associated with impaired placental signaling pathways, increased pro-oxidant/pro-inflammatory environment and fetal overgrowth.
糖尿病家族史易患妊娠期糖尿病（GDM）。我们假设孕前糖尿病大鼠的雌性后代会发生GDM，这是一种与胎儿过度生长和胎盘信号改变相关的病理状态。我们发现孕前糖尿病大鼠的后代在3个月大时血糖和胰岛素水平正常。然而，与对照组相比，母体高血糖和高胰岛素血症以及胎儿体重增加在GDM中很明显。在这个宫内程序化GDM模型中，胎盘显示mTOR途径有改变：尽管4EBP-1和PKCα的总表达减少，但4EBP-1和PKCα的磷酸化未改变，而SGK1的磷酸化增加。GDM胎盘还显示PPARα和PPARγ的表达减少，脂质过氧化增加、一氧化氮产生增加以及过氧亚硝酸盐诱导的损伤增加。我们得出结论，子宫内母体糖尿病暴露会使雌性后代发生程序化GDM，导致与胎盘信号通路受损、促氧化剂/促炎环境增加和胎儿过度生长相关的GDM模型。
