ArticlePloS one2019
Genetic resistance to DEHP-induced transgenerational endocrine disruption.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 26 citations in OpenAlex.
- Adaptation in the Alleyways: Candidate Genes Under Potential Selection in Urban Coyotes.Genome biology and evolution · 2025Article
- Phthalates and epigenetics: An emerging public health concern.Current research in toxicology · 2025Review
- Candidate biomarkers from the integration of methylation and gene expression in discordant autistic sibling pairs.Translational psychiatry · 2023Article
- Transposable Elements and Human Diseases: Mechanisms and Implication in the Response to Environmental Pollutants.International journal of molecular sciences · 2022Review
- REPRODUCTIVE TOXICOLOGY: Environmental exposures, fetal testis development and function: phthalates and beyond.Reproduction (Cambridge, England) · 2021Review
- Epi-mutations for spermatogenic defects by maternal exposure to di(2-ethylhexyl) phthalate.eLife · 2021Article
- Perinatal DEHP exposure induces sex- and tissue-specific DNA methylation changes in both juvenile and adult mice.Environmental epigenetics · 2021Article
- Autism spectrum disorder at the crossroad between genes and environment: contributions, convergences, and interactions in ASD developmental pathophysiology.Molecular autism · 2020Review
- Multi and transgenerational epigenetic effects of di-(2-ethylhexyl) phthalate (DEHP) in liver.Toxicology and applied pharmacology · 2020Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Di(2-ethylhexyl)phthalate (DEHP) interferes with sex hormones signaling pathways (SHP). C57BL/6J mice prenatally exposed to 300 mg/kg/day DEHP develop a testicular dysgenesis syndrome (TDS) at adulthood, but similarly-exposed FVB/N mice are not affected. Here we aim to understand the reasons behind this drastic difference that should depend on the genome of the strain. In both backgrounds, pregnant female mice received per os either DEHP or corn oil vehicle and the male filiations were examined. Computer-assisted sperm analysis showed a DEHP-induced decreased sperm count and velocities in C57BL/6J. Sperm RNA sequencing experiments resulted in the identification of the 62 most differentially expressed RNAs. These RNAs, mainly regulated by hormones, produced strain-specific transcriptional responses to prenatal exposure to DEHP; a pool of RNAs was increased in FVB, another pool of RNAs was decreased in C57BL/6J. In FVB/N, analysis of non-synonymous single nucleotide polymorphisms (SNP) impacting SHP identified rs387782768 and rs29315913 respectively associated with absence of the Forkhead Box A3 (Foxa3) RNA and increased expression of estrogen receptor 1 variant 4 (NM_001302533) RNA. Analysis of the role of SNPs modifying SHP binding sites in function of strain-specific responses to DEHP revealed a DEHP-resistance allele in FVB/N containing an additional FOXA1-3 binding site at rs30973633 and four DEHP-induced beta-defensins (Defb42, Defb30, Defb47 and Defb48). A DEHP-susceptibility allele in C57BL/6J contained five SNPs (rs28279710, rs32977910, rs46648903, rs46677594 and rs48287999) affecting SHP and six genes (Svs2, Svs3b, Svs4, Svs3a, Svs6 and Svs5) epigenetically silenced by DEHP. Finally, targeted experiments confirmed increased methylation in the Svs3ab promoter with decreased SEMG2 persisting across generations, providing a molecular explanation for the transgenerational sperm velocity decrease found in C57BL/6J after DEHP exposure. We conclude that the existence of SNP-dependent mechanisms in FVB/N inbred mice may confer resistance to transgenerational endocrine disruption.
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