ArticlePloS one2017
Testicular Dysgenesis Syndrome and Long-Lasting Epigenetic Silencing of Mouse Sperm Genes Involved in the Reproductive System after Prenatal Exposure to DEHP.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 64 citations in OpenAlex.
- Are infertile men at a higher risk of morbidity and early mortality?Human reproduction (Oxford, England) · 2026Review
- Genetic variants (LhcgrBiology of sex differences · 2025Article
- Phthalates and epigenetics: An emerging public health concern.Current research in toxicology · 2025Review
- Prenatal DEHP exposure induces lifelong testicular toxicity by continuously interfering with steroidogenic gene expression.Translational andrology and urology · 2024Article
- A novel approach for predicting upstream regulators (PURE) that affect gene expression.Scientific reports · 2023Article
- Epigenetics, cryptorchidism, and infertility.Basic and clinical andrology · 2023Article
- Mono(2-ethylhexyl) phthalate induces transcriptomic changes in placental cells based on concentration, fetal sex, and trophoblast cell type.Archives of toxicology · 2023Article
- Modulation of fetoplacental growth, development and reproductive function by endocrine disrupters.Frontiers in endocrinology · 2023Review
- Inheritance of environment-induced phenotypic changes through epigenetic mechanisms.Environmental epigenetics · 2023Review
- Identification of spermatogenesis-associated changes in DNA methylation induced by maternal exposure to chemicals in male germ cells.STAR protocols · 2022Article
- Developmental origins of adult diseases.Medical review (2021) · 2022Review
- Transposable Elements and Human Diseases: Mechanisms and Implication in the Response to Environmental Pollutants.International journal of molecular sciences · 2022Review
- Integrated Genomic and Bioinformatics Approaches to Identify Molecular Links between Endocrine Disruptors and Adverse Outcomes.International journal of environmental research and public health · 2022Review
- The ameliorative effect of ellagic acid on di-(2-ethylhexyl) phthalate-induced testicular structural alterations, oxidative stress, inflammation and sperm damages in adult mice.Reproductive biology and endocrinology : RB&E · 2021Article
- Epi-mutations for spermatogenic defects by maternal exposure to di(2-ethylhexyl) phthalate.eLife · 2021Article
- Transgenerational Effects of Di(2-Ethylhexyl) Phthalate on Anogenital Distance, Sperm Functions and DNA Methylation in Rat Offspring.International journal of molecular sciences · 2021Article
- Prenatal di-(2-ethylhexyl) phthalate maternal exposure impairs the spatial memory of adult mouse offspring in a phase- and gender-dependent manner.Environmental science and pollution research international · 2020Article
- RXFP2 as novel potential biomarker for abnormal differentiation induced by diethylstilbestrol in the gubernaculum of fetal mice.American journal of translational research · 2020Article
- The Promises and Challenges of Toxico-Epigenomics: Environmental Chemicals and Their Impacts on the Epigenome.Environmental health perspectives · 2020Article
- A Novel Approach to Chemical Mixture Risk Assessment-Linking Data from Population-Based Epidemiology and Experimental Animal Tests.Risk analysis : an official publication of the Society for Risk Analysis · 2019Article
Corrections and comments
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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
The endocrine disruptor bis(2-ethylhexyl) phthalate (DEHP) has been shown to exert adverse effects on the male animal reproductive system. However, its mode of action is unclear and a systematic analysis of its molecular targets is needed. In the present study, we investigated the effects of prenatal exposure to 300 mg/kg/day DEHP during a critical period for gonads differentiation to testes on male mice offspring reproductive parameters, including the genome-wide RNA expression and associated promoter methylation status in the sperm of the first filial generation. It was observed that adult male offspring displayed symptoms similar to the human testicular dysgenesis syndrome. A combination of sperm transcriptome and methylome data analysis allowed to detect a long-lasting DEHP-induced and robust promoter methylation-associated silencing of almost the entire cluster of the seminal vesicle secretory proteins and antigen genes, which are known to play a fundamental role in sperm physiology. It also resulted in the detection of a DEHP-induced promoter demethylation associated with an up-regulation of three genes apparently not relevant for sperm physiology and partially related to the immune system. As previously reported, DEHP induced an increase in mir-615 microRNA expression and a genome-wide decrease in microRNA promoter methylation. A functional analysis revealed DEHP-induced enrichments in down-regulated gene transcripts coding for peroxisome proliferator-activated receptors and tumor necrosis factor signaling pathways, and in up-regulated gene transcripts coding for calcium binding and numerous myosin proteins. All these enriched pathways and networks have been described to be associated in some way with the reproductive system. This study identifies a large new array of genes dysregulated by DEHP that may play a role in the complex system controlling the development of the male reproductive system.
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