Fetal e-cigarette exposure programs a neonatal brain hypoxic-ischemic sensitive phenotype via altering DNa methylation patterns and autophagy signaling pathway.

Introduction:
This article investigates the effects of fetal exposure to e-cigarette aerosols on neonatal growth, brain development, and vulnerability to hypoxic-ischemic encephalopathy (hIE). The study uses a chronic intermittent e-cigarette aerosol exposure (CIEC) pregnant rat model and an established hIE model to examine the impact of e-cigarette exposure on neonatal growth, brain development, and hIE susceptibility. The study also explores the potential epigenetic regulatory mechanisms that may link maternal e-cigarette vaping to altered neurodevelopmental outcomes in offspring.

Key Points:

* The study used a CIEC pregnant rat model to expose time-dated pregnant rats to e-cigarette aerosols (2.4% nicotine) or fresh air from gestational day 4 to gestational day 20.
* Neonatal offspring were examined at postnatal day 9 (P9) for body weight, brain weight, and brain-to-body weight ratio.
* The hIE model was conducted on P9 pups to assess hypoxic-ischemia-induced brain injury in both control and e-cigarette exposed groups.
* Global DNa methylation levels and CpG island methylation levels at the aTG5 promoter region were examined in neonatal brains.
* autophagy-related gene and protein abundances were analyzed to determine their potential contributions to e-cigarette exposure-induced programming of a brain hypoxic-ischemic sensitive phenotype.
* Maternal e-cigarette exposure decreased neonatal body weight and brain weight, but increased the brain-to-body weight ratio.
* E-cigarette exposure exaggerated hI-induced brain injury in male neonatal offspring, and altered DNa methylation patterns and specific CpG methylation at the aTG5 promoter region in neonatal brains.
* E-cigarette exposure suppressed autophagy-related gene expression and sirtuin 1 expression in neonatal brains, and knockdown of aTG5 enhanced hI-induced brain injury in neonatal rat brain.

Main Message:
The study provides novel evidence that fetal e-cigarette exposure during pregnancy restricts offspring growth and brain development, leading to programming of a brain hypoxic-ischemia sensitive phenotype in postnatal life. The study suggests that e-cigarette exposure during pregnancy is an important risk factor and perinatal insult that can cause offspring growth restriction and induce a fetal programming of neonatal brain hypoxic-ischemia sensitive phenotype via DNa methylation epigenetic regulation of autophagy signaling pathway. The findings highlight the need for further research to understand the long-term effects of e-cigarette exposure during pregnancy on offspring neurodevelopmental outcomes.

Walayat a, Li Y, Zhang Y, et al. Fetal e-cigarette exposure programs a neonatal brain hypoxic-ischemic sensitive phenotype via altering DNa methylation patterns and autophagy signaling pathway. american journal of physiology Regulatory, integrative and comparative physiology. 2021;321(5):R791-R801. doi:10.1152/ajpregu.00207.2021