Evidence map›Paper›PMID 34524928›Full record

ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2021

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

Andrew Walayat, Yong Li, Yanyan Zhang, Yingjie Fu, Bailin Liu, Xuesi M Shao, Lubo Zhang, Daliao Xiao

Open access · greenAbstract read
In one paragraph

Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.

  1. Pooled it
  2. Prenatal Cannabis and Tobacco: Studies in Animal Models.Advances in experimental medicine and biology · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Maternal use of electronic cigarettes and impact on offspring: a double-hit model.Journal of applied physiology (Bethesda, Md. : 1985) · 2024
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Andrew WalayatLawrence D. Longo MD Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California.
Yong LiLawrence D. Longo MD Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California.
Yanyan ZhangLawrence D. Longo MD Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California.
Yingjie FuLawrence D. Longo MD Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California.
Bailin LiuLawrence D. Longo MD Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California.
Xuesi M ShaoDepartment of Neurobiology, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California.ORCID 0000-0002-5165-347X
Lubo ZhangLawrence D. Longo MD Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California.
Daliao XiaoLawrence D. Longo MD Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California.ORCID 0000-0003-0147-2758
Loma Linda University · USUniversity of California, Los Angeles · US

Funding

Gestational Hypoxia and Programming of Maternal, Fetal and Newborn Vascular FunctionR01HL149608 · NHLBI · LOMA LINDA UNIVERSITY · PI PEARCE, WILLIAM J., WILSON, SEAN M · 2020 to 2023
$3.1M
Maternal inhaled nicotine leads to aberrant development of hypertensive phenotypeR01HL135623 · NHLBI · LOMA LINDA UNIVERSITY · PI SHAO, XUESI MAX, XIAO, DALIAO · 2017 to 2021
$2.3M
miRNA as a novel therapeutic target in antenatal nicotine-induced ischemic heartR01HD088039 · NICHD · LOMA LINDA UNIVERSITY · PI XIAO, DALIAO · 2017 to 2021
$1.6M
Developing an efficient E-cigarette aerosol generation and exposure system for rodent models with aerosol characteristics equivalent to those inhaled by E-cigarette usersR42DA044788 · NIDA · AUTOMATE SCIENTIFIC, INC. · PI KEWEKORDES, JOSEF, SHAO, XUESI MAX · 2019 to 2020
$884k
Nicotine-mediated fetal programming of vascular dysfunction phenotypeR03DA041492 · NIDA · LOMA LINDA UNIVERSITY · PI XIAO, DALIAO · 2017 to 2018
$158k
NHLBI NIH HHS R01 HL135623NHLBI NIH HHS R01 HL149608NICHD NIH HHS R01 HD088039NIDA NIH HHS R03 DA041492NIDA NIH HHS R42 DA044788
6 · The paper itself

Abstract

Maternal e-cigarette (e-cig) exposure is a pressing perinatal health concern. Emerging evidence reveals its potential adverse impacts on brain development in offspring, yet the underlying mechanisms are poorly understood. The present study tested the hypothesis that fetal e-cig exposure induces an aberrant DNA methylation profile in the developing brain, leading to alteration of autophagic flux signaling and programming of a sensitive phenotype to neonatal hypoxic-ischemic encephalopathy (HIE). Pregnant rats were exposed to chronic intermittent e-cig aerosol. Neonates were examined at the age of 9 days old. Maternal e-cig exposure decreased the body weight and brain weight but enhanced the brain-to-body weight ratio in the neonates. E-cig exposure induced a gender-dependent increase in hypoxic-ischemia-induced brain injury in male neonates associated with enhanced reactive oxygen species (ROS) activity. It differentially altered DNA methyltransferase expression and enhanced both global DNA methylation levels and specific CpG methylation at the autophagy-related gene 5 (ATG5) promoter. In addition, maternal e-cig exposure caused downregulations of ATG5, microtubule-associated protein 1 light chain 3β, and sirtuin 1 expression in neonatal brains. Of importance, knockdown of ATG5 in neonatal pups exaggerated neonatal HIE. In conclusion, the present study reveals that maternal e-cig exposure downregulates autophagy-related gene expression via DNA hypermethylation, leading to programming of a hypoxic-ischemic sensitive phenotype in the neonatal brain.

Indexed as

AutophagyDNA MethylationElectronic Nicotine Delivery SystemsEpigenesis, GeneticPrenatal Exposure Delayed EffectsAnimalsAnimals, NewbornAutophagy-Related Protein 5BrainCpG IslandsE-Cigarette VaporFemaleGestational AgeHypoxia-Ischemia, BrainInhalation ExposureMaternal ExposureAnxa3 protein, ratAtg5 protein, ratAutophagy-Related Protein 5E-Cigarette VaporMicrotubule-Associated ProteinsSirt1 protein, ratSirtuin 1autophagyDNA methylatione-cigaretteHIEROS

Identifiers

PMID34524928
PMCPMC8616627
OpenAlexW3200856037

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.