Cardiovascular Consequences of Late-Gestational Hypoxia in Adult Female Rat Offspring and the Effects of Maternal Ergothioneine Treatment.

Abstract

Prenatal hypoxia (PH) predisposes offspring to cardiovascular diseases. While maternal antioxidant treatment can normalize blood pressure (BP) in offspring, it typically requires high doses that may harm both mother and fetus. The antioxidant ergothioneine (ERG), noted for its very low toxicity, has emerged as a promising candidate. Because PH-induced changes have been primarily studied in male offspring, this study was performed to investigate the impact of maternal ERG treatment and late-gestational PH on cardiovascular outcomes in adult female rat offspring. Pregnant Wistar rats were exposed to 10.5 % O2 for 4 h on gestational days (GDs) 19 and 20. Adult offspring were implanted with telemetry sensors for continuous BP and heart rate (HR) monitoring. In a second experiment, pregnant rats received ERG (35 mg/kg/day) from GD6 until delivery, and on GD20 were exposed to 10.5 % O2 for 12 h. Cardiac and renal protein expression in adult offspring was analysed by western blot. PH offspring exhibited lower HR and BP responses to restraint stress than did controls. PH increased the low-to-high frequency ratio (a marker of sympathovagal balance; P=0.051) and the standard deviation of normal-to-normal interbeat intervals (P=0.024). Despite normal cardiovascular parameters at rest, late-gestational PH programmed subtle yet lasting changes in sympathovagal balance and impaired cardiovascular reactivity to stress in adult female offspring. ERG upregulated beta1-adrenergic receptor and endothelial nitric oxide synthase, particularly in the PH group. This selective effect highlights ERG's potential as a targeted antioxidant intervention against harmful prenatal conditions. Key words Ergothioneine " Prenatal hypoxia " Female " Cardiovascular " Telemetry.