Evidence map›Paper›PMID 29024969›Full record

ArticleHuman reproduction (Oxford, England)2017

Preconception urinary phthalate concentrations and sperm DNA methylation profiles among men undergoing IVF treatment: a cross-sectional study.

Haotian Wu, Molly S Estill, Alexander Shershebnev, Alexander Suvorov, Stephen A Krawetz, Brian W Whitcomb, Holly Dinnie, Tayyab Rahil, Cynthia K Sites, J Richard Pilsner

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human reproduction (Oxford, England), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 2 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

56 citing papers in PubMed, 2 syntheses or guidelines pooled it, 113 citations in OpenAlex.

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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

10 authors at 3 institutions in 1 country.

Haotian WuDepartment of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts Amherst, 173A Goessmann, 686 North Pleasant Street, Amherst, MA 01003, USA.
Molly S EstillCenter for Molecular Medicine and Genetics, Wayne State University School of Medicine, 3127 Scott Hall, 540 East Canfield, Detroit, MI 48201, USA.
Alexander ShershebnevDepartment of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts Amherst, 173A Goessmann, 686 North Pleasant Street, Amherst, MA 01003, USA.
Alexander SuvorovDepartment of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts Amherst, 173A Goessmann, 686 North Pleasant Street, Amherst, MA 01003, USA.
Stephen A KrawetzCenter for Molecular Medicine and Genetics, Wayne State University School of Medicine, 3127 Scott Hall, 540 East Canfield, Detroit, MI 48201, USA.
Brian W WhitcombDepartment of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, 715 North Pleasant Street Amherst, MA 01003, USA.
Holly DinnieDepartment of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Baystate Medical Center, 759 Chestnut Street, Springfield, MA 01199, USA.
Tayyab RahilDepartment of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Baystate Medical Center, 759 Chestnut Street, Springfield, MA 01199, USA.
Cynthia K SitesDepartment of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Baystate Medical Center, 759 Chestnut Street, Springfield, MA 01199, USA.
J Richard PilsnerDepartment of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts Amherst, 173A Goessmann, 686 North Pleasant Street, Amherst, MA 01003, USA.
University of Massachusetts Amherst · USBaystate Medical Center · USWayne State University · US

Funding

Phthalate Exposure, Sperm DNA Methylation and Early-life DevelopmentK22ES023085 · NIEHS · UNIVERSITY OF MASSACHUSETTS AMHERST · PI PILSNER, J. RICHARD · 2014 to 2016
$441k
6 · The paper itself

Abstract

study questionAre preconception phthalate and phthalate replacements associated with sperm differentially methylated regions (DMRs) among men undergoing IVF? SUMMARY ANSWER: Ten phthalate metabolites were associated with 131 sperm DMRs that were enriched in genes related to growth and development, cell movement and cytoskeleton structure. WHAT IS KNOWN ALREADY: Several phthalate compounds and their metabolites are known endocrine disrupting compounds and are pervasive environmental contaminants. Rodent studies report that prenatal phthalate exposures induce sperm DMRs, but the influence of preconception phthalate exposure on sperm DNA methylation in humans is unknown. STUDY DESIGN, SIZE, DURATION: An exploratory cross-sectional study with 48 male participants from the Sperm Environmental Epigenetics and Development Study (SEEDS). PARTICIPANTS/MATERIALS, SETTING,

methodsThe first 48 couples provided a spot urine sample on the same day as semen sample procurement. Sperm DNA methylation was assessed with the HumanMethylation 450 K array. Seventeen urinary phthalate and 1,2-Cyclohexane dicarboxylic acid diisononyl ester (DINCH) metabolite concentrations were measured from spot urine samples. The A-clust algorithm was employed to identify co-regulated regions. DMRs associated with urinary metabolite concentrations were identified via linear models, corrected for false discovery rate (FDR). MAIN RESULTS AND ROLE OF CHANCE: Adjusting for age, BMI, and current smoking, 131 DMRs were associated with at least one urinary metabolite. Most sperm DMRs were associated with anti-androgenic metabolites, including mono(2-ethylhexyl) phthalate (MEHP, n = 83), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP, n = 16), mono-n-butyl phthalate (MBP, n = 22) and cyclohexane-1,2-dicarboxylic acid-monocarboxy isooctyl (MCOCH, n = 7). The DMRs were enriched in lincRNAs as well as in regions near coding regions. Functional analyses of DMRs revealed enrichment of genes related to growth and development as well as cellular function and maintenance. Finally, 13% of sperm DMRs were inversely associated with high quality blastocyst-stage embryos after IVF. LIMITATIONS, REASONS FOR CAUTION: Our modest sample size only included 48 males and additional larger studies are necessary to confirm our observed results. Non-differential misclassification of exposure is also a concern given the single spot urine collection. WIDER IMPLICATIONS OF THE

findingsTo our knowledge, this is the first study to report that preconception urinary phthalate metabolite concentrations are associated with sperm DNA methylation in humans. These results suggest that paternal adult environmental conditions may influence epigenetic reprogramming during spermatogenesis, and in turn, influence early-life development. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grant K22-ES023085 from the National Institute of Environmental Health Sciences. The authors declare no competing interests.

Indexed as

Fertilization in VitroAdultCross-Sectional StudiesDNA MethylationFemaleHumansInfertilityMalePhthalic AcidsSpermatozoaphthalic acidPhthalic AcidsblastocystDNADNA methylationearly lifeembryoendocrine disruptorsepigeneticsphthalatespreconceptionsperm

Identifiers

PMID29024969
PMCPMC5850785
OpenAlexW2754252053

What OpenQuestion holds

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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.