Evidence map›Paper›PMID 34120004›Full record

ArticleEnvironment international2021

Paternal preconception phthalate exposure alters sperm methylome and embryonic programming.

Oladele A Oluwayiose, Chelsea Marcho, Haotian Wu, Emily Houle, Stephen A Krawetz, Alexander Suvorov, Jesse Mager, J Richard Pilsner

Open access · goldAbstract read
In one paragraph

Article in Environment international, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
6.0field-weighted citation impact, top 3% 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

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.

  1. Pooled it
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  6. Progeny effects of rotenone exposure depend on parental toxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2026
    Article
  7. Article
  8. Endocrine Disrupting Agents: Toxicological Aspects on Male Reproduction.Reproductive sciences (Thousand Oaks, Calif.) · 2025
    Review
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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 3 institutions in 1 country.

Oladele A OluwayioseDepartment of Environmental Health Sciences, University of Massachusetts Amherst, Amherst, MA, USA.
Chelsea MarchoDepartment of Environmental Health Sciences, University of Massachusetts Amherst, Amherst, MA, USA; Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, MA, USA.
Haotian WuDepartment of Environmental Health Sciences, Mailman School of Public Health, Columbia University, NY, USA.
Emily HouleDepartment of Environmental Health Sciences, University of Massachusetts Amherst, Amherst, MA, USA.
Stephen A KrawetzDepartment of Obstetrics and Gynecology & Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.
Alexander SuvorovDepartment of Environmental Health Sciences, University of Massachusetts Amherst, Amherst, MA, USA.
Jesse MagerDepartment of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, MA, USA.
J Richard PilsnerDepartment of Environmental Health Sciences, University of Massachusetts Amherst, Amherst, MA, USA; Department of Obstetrics and Gynecology & Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA. Electronic address: rpilsner@wayne.edu.
University of Massachusetts Amherst · USWayne State University · USColumbia University · US

Funding

Pilot Project ProgramP30ES020957 · NIEHS · WAYNE STATE UNIVERSITY · PI RUDEN, DOUGLAS M · 2014 to 2021
$10.1M
Male preconception phthalates and offspring embryo and sperm allele-specific methylome programming.R01ES028214 · NIEHS · WAYNE STATE UNIVERSITY · PI PILSNER, J. RICHARD · 2017 to 2021
$2.3M
Determining how preconception exposure to phthalates impacts sperm function, the epigenome fertility and reproductive outcomes in mice and menR01ES030942 · NIEHS · WAYNE STATE UNIVERSITY · PI PILSNER, J. RICHARD · 2019 to 2021
$1.5M
Embryonic inheritance of sperm methylome after adult exposure to phthalatesR21ES026778 · NIEHS · UNIVERSITY OF MASSACHUSETTS AMHERST · PI MAGER, JESSE, PILSNER, J. RICHARD · 2016 to 2017
$449k
NIEHS NIH HHS P30 ES020957NIEHS NIH HHS R01 ES028214NIEHS NIH HHS R01 ES030942NIEHS NIH HHS R21 ES026778
6 · The paper itself

Abstract

Preconception environmental conditions have been demonstrated to shape sperm epigenetics and subsequently offspring health and development. Our previous findings in humans showed that urinary anti-androgenic phthalate metabolites in males were associated with altered sperm methylation and blastocyst-stage embryo development. To corroborate this, we examined the effect of preconception exposure to di(2-ethylhexyl) phthalate (DEHP) on genome-wide DNA methylation and gene expression profiles in mice. Eight-week old C57BL/6J male mice were exposed to either a vehicle control, low, or high dose of DEHP (2.5 and 25 mg/kg/weight, respectively) for 67 days (~2 spermatogenic cycles) and were subsequently mated with unexposed females. Reduced representation bisulfite sequencing (RRBS) of epididymal sperm was performed and gastrulation stage embryos were collected for RRBS and transcriptome analyses in both embryonic and extra-embryonic lineages. Male preconception DEHP exposure resulted in 704 differentially methylated regions (DMRs; q-value < 0.05; ≥10% methylation change) in sperm, 1,716 DMRs in embryonic, and 3,181 DMRs in extra-embryonic tissue. Of these, 29 DMRs overlapped between sperm and F1 tissues, half of which showed concordant methylation changes between F0 and F1 generations. F1 transcriptomes at E7.5 were also altered by male preconception DEHP exposure including developmental gene families such as Hox, Gata, and Sox. Additionally, gene ontology analyses of DMRs and differentially expressed genes showed enrichment of multiple developmental processes including embryonic development, pattern specification and morphogenesis. These data indicate that spermatogenesis in adult may represent a sensitive window in which exposure to DEHP alters the sperm methylome as well as DNA methylation and gene expression in the developing embryo.

Indexed as

Diethylhexyl PhthalateEpigenomeAnimalsDNA MethylationEmbryonic DevelopmentFemaleMaleMiceMice, Inbred C57BLPhthalic AcidsPregnancySpermatozoaDiethylhexyl Phthalatephthalic acidPhthalic AcidsDEHPDi(2-ethylhexyl) phthalateDifferential gene expressionDNA methylationEmbryonic developmentSperm

Identifiers

PMID34120004
PMCPMC8292217
OpenAlexW3168567535

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Registered trials

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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.