Analysis of Maternal and Fetal Cardiovascular Systems During Hyperglycemic Pregnancy in the Non-Obese Diabetic Mouse

摘要

Pre-conception or gestationally-induced diabetes increases morbidities and elevates long-term cardiovascular disease risks in women and their children. Spontaneously hyperglycemic (d)-NOD/ShiLtJ females, a type 1 diabetes model, develop bradycardia and hypotension after midpregnancy compared with normoglycemic, age and gestation day (gd)-matched controls (c-NOD). We hypothesized that onset of the placental circulation at gd9–10 and rapid fetal growth from gd14 correlate with aberrant hemodynamic outcomes in d-NOD females. To develop further gestational time course correlations between maternal cardiac and renal parameters, high-frequency ultrasonography was applied to virgin and gd8–16 d- and c-NODs. Cardiac output and left ventricular (LV) mass increased in c- but not d-NODs. Ultrasound and postmortem histopathology showed overall greater LV dilation in d- than c-NOD mice in mid-late gestation. These changes suggest blunted remodeling and altered functional adaptation of d-NOD hearts. Umbilical cord ultrasounds revealed lower fetal heart rates from gd12 and lower umbilical flow velocities at gd14 and 16 in d- versus c-NOD pregnancies. From gd14–16, d-NOD fetal losses exceeded those of c-NOD. Similar aberrant responses in human diabetic pregnancies may elevate postpartum maternal and child cardiovascular risk, particularly if mothers lack adequate prenatal care or have poor glycemic control over gestation.