Chronic hypoxia alters maternal uterine and fetal hemodynamics in the full-term pregnant guinea pig

Abstract

Placental hypoxia is associated with maternal hypertension, placental insufficiency, and fetal growth restriction. In the pregnant guinea pig, prenatal hypoxia during early gestation inhibits cytotrophoblast invasion of spiral arteries, increases maternal blood pressure, and induces fetal growth restriction. In this study the impact of chronic maternal hypoxia on fetal heart structure was evaluated using four-dimensional echocardiography with spatiotemporal image correlation and tomographic ultrasound, and uterine and umbilical artery resistance/pulsatility indexes and fetal heart function were evaluated using pulsed-wave Doppler ultrasound. Pregnant guinea pigs were exposed to normoxia ( = 7) or hypoxia (10.5% O, = 9) at 28-30 days gestation, which was maintained until full term (65 days). At full term, fetal heart structure and outflow tracts were evaluated in the four-chamber view. Fetal heart diastolic function was assessed by E wave-to-A wave diastolic filling ratios (E/A ratios) of both ventricles and systolic function by the myocardial performance index (or Tie) of left ventricles of normoxic ( = 21) and hypoxic ( = 17) fetuses. There were no structural abnormalities in fetal hearts. However, hypoxia induced asymmetric fetal growth restriction and increased the placental/fetal weight compared with normoxic controls. Hypoxia increased Doppler resistance and pulsatility indexes in the uterine, but not umbilical, arteries, had no effect on the Tie index, and increased the E/A ratio in left, but not right, ventricles. Thus, prolonged hypoxia, starting at midgestation, increases uterine artery resistance and generates fetal growth restriction at full term. Furthermore, the enhanced cardiac diastolic filling with no changes in systolic function or umbilical artery resistance suggests that the fetal guinea pig systemic circulation undergoes a compensated, adaptive response to prolonged hypoxia exposure.

Prenatal hypoxia impairs cardiac mitochondrial and ventricular function in guinea pig offspring in a sex-related manner

“…Time-mated pregnant guinea pigs were randomly assigned to normoxia (NMX, room air) or hypoxia (HPX, 10.5% O 2) treatment and exposed to NMX during the entire gestation or to HPX during the last 14 days of pregnancy, a period of rapid fetal growth and increased O2 utilization by the fetus. Chronic hypoxia does not reduce either maternal food or water intake and, therefore, represents a hypoxic model without nutrient restriction (80). Pregnant sows were allowed to deliver vaginally, and pups born into a hypoxic environment were removed to normal room air within 1 day of delivery.…”

Models of Intrauterine growth restriction and fetal programming in rabbits

“…It is also a main cause of IUGR at high altitude. Whilst the impact of hypoxia on fetal growth and developmental programming has been widely studied in rodents (Aljunaidy, Morton, Cooke, & Davidge, ; Higgins, Vaughan, Fernandez de Liger, Fowden & Sferruzzi‐Perri, ; Turan, Aberdeen, & Thompson, ) and sheep (Allison et al, ; Herrera et al, ; Parraguez et al, ), few researchers have used the rabbit as an animal model. In pregnant rabbits, continuous exposure to hypobaric oxygen conditions (13.2% oxygen equivalent to 3,657 m) from GD14, decreased fetal and placental weight at GD30–31 (Chang, Rutledge, Stoops, & Abbe, ).…”

Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic

“…), experimentally induced placental dysfunction in the guinea pig (Turan et al . ) may contribute to our understanding of the ‘programming’ of later heart dysfunction in offspring of a high‐risk pregnancy.…”