Evidence map›Paper›PMID 31064411›Full record

ArticleClinical epigenetics2019

Casp8 hypomethylation and neural tube defects in association with polycyclic aromatic hydrocarbon exposure.

Yun Huang, Aiguo Ren, Linlin Wang, Lei Jin, Shanshan Lin, Zhiwen Li, Jasmine A McDonald

Open access · goldAbstract read
In one paragraph

Article in Clinical epigenetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

8 citing papers in PubMed, 19 citations in OpenAlex.

  1. CombinedActa biochimica et biophysica Sinica · 2025
    Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Neural Tube Defects andFrontiers in cell and developmental biology · 2020
    Article
  8. Article
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

7 authors at 2 institutions in 2 countries.

Yun HuangInstitute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing, 100191, China.ORCID 0000-0001-9115-5638
Aiguo RenInstitute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing, 100191, China. renag@bjmu.edu.cn.
Linlin WangInstitute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing, 100191, China. linlinwang@bjmu.edu.cn.
Lei JinInstitute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing, 100191, China.
Shanshan LinInstitute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing, 100191, China.
Zhiwen LiInstitute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing, 100191, China.
Jasmine A McDonaldDepartment of Epidemiology, Mailman School of Public Health, Columbia University Medical Center, 722 West 168th Street, New York, NY, 10032, USA.
Peking University · CNColumbia University Irving Medical Center · US

Funding

True Metal fac coreP30ES009089 · NIEHS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MATTHEW S PERZANOWSKI · 1998 to 2026
$44.7M
6 · The paper itself

Abstract

backgroundEpidemiological studies have found that prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with increased risk for neural tube defects (NTDs). Aberrant DNA methylation, excessive apoptosis, and oxidative stress have been implied as the mechanism underlying the association between PAH exposure and NTDs, respectively. However, the role of DNA methylation aberration of apoptotic initiator CASP8 (caspase-8, apoptosis-related cysteine peptidase) in the formation of NTDs in association with PAH exposure is not known. By combining a case-control study and mouse model, we aimed to explore the full spectrum of the links from PAH exposure, oxidative stress, CASP8 methylation change, caspase-8 activation, apoptosis, to NTD formation.

resultsHypomethylation of CASP8 promoter was noticed in the microarray profiled by Infinium HumanMethylation450 BeadChip using neural tissues from 10 terminated NTD fetuses and 8 terminated non-malformed fetuses (14 CpG sites, with β difference ranging between 8.8 and 26.3%), and was validated in a larger case-control sample performed with neural tissues from 80 NTD cases and 32 non-malformed fetuses, using the Sequenom MassARRAY system (7 CpG sites). Hypomethylation of CASP8 was a risk factor for NTDs (aOR = 1.11; 95% CI, 1.05-1.17) based on the logistic regression model. According to Pearson's correlation, methylation levels of CASP8 were inversely correlated with PAH concentrations in maternal serum and with oxidative stress markers in fetal neural tissues (p < 0.05). In the animal study, increased NTD rates (13.5% frequency), Casp8 hypomethylation, caspase-8 upregulation, increased caspase-8 cleavage, and excessive apoptosis were found in mouse embryos cultured with benz(a)pyrene (BaP) in vitro. Antioxidant N-acetyl-L-cysteine (NAC) and BaP co-treatment attenuated the changes found in BaP treatment group.

conclusionsHypomethylation of Casp8 promoter is associated with the formation of NTDs, and Casp8 hypomethylation may be induced by oxidative stress that resulted from exposure to PAHs.

Indexed as

AnimalsCase-Control StudiesCaspase 8Disease Models, AnimalDNA MethylationEpigenesis, GeneticFemaleGenetic Predisposition to DiseaseHumansMaternal ExposureMaternal-Fetal ExchangeMiceNeural Tube DefectsOxidative StressPolycyclic Aromatic HydrocarbonsPregnancyCASP8 protein, humanCaspase 8Polycyclic Aromatic HydrocarbonsApoptosisCaspase-8HypomethylationNeural tube defectsOxidative stressPolycyclic aromatic hydrocarbons

Identifiers

PMID31064411
PMCPMC6505285
OpenAlexW2946240279

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.