ArticleEnvironmental health perspectives2012
Human fetal testis xenografts are resistant to phthalate-induced endocrine disruption.
Article in Environmental health perspectives, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.
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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.
The trial behind it
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Who cites it
40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 96 citations in OpenAlex.
- Effect of environmental and pharmaceutical exposures on fetal testis development and function: a systematic review of human experimental data.Human reproduction update · 2019Pooled it
- Systematic reviews and meta-analyses of human and animal evidence of prenatal diethylhexyl phthalate exposure and changes in male anogenital distance.Journal of toxicology and environmental health. Part B, Critical reviews · 2018Pooled it
- Genetic, Epigenetic, and Non-Genetic Factors in Testicular Dysgenesis Syndrome: A Narrative Review.Genes · 2025Review
- Dose-response assessment of dipentyl phthalate effects on testosterone production and morphogenesis of late-gestation fetal rat testis.Environment international · 2025Article
- Impact of Fetal Exposure to Endocrine Disrupting Chemical Mixtures on FOXA3 Gene and Protein Expression in Adult Rat Testes.International journal of molecular sciences · 2023Article
- Impact of endocrine disrupting chemicals and pharmaceuticals on Sertoli cell development and functions.Frontiers in endocrinology · 2023Review
- Interaction between mono-(2-ethylhexyl) phthalate and retinoic acid alters Sertoli cell development during fetal mouse testis cord morphogenesis.Current research in toxicology · 2022Article
- REPRODUCTIVE TOXICOLOGY: Environmental exposures, fetal testis development and function: phthalates and beyond.Reproduction (Cambridge, England) · 2021Review
- Six Decades of Research on Human Fetal Gonadal Steroids.International journal of molecular sciences · 2021Review
- Effects of endocrine disruptors on fetal testis development, male puberty, and transition age.Endocrine · 2021Review
- Development of a putative adverse outcome pathway network for male rat reproductive tract abnormalities with specific considerations for the androgen sensitive window of development.Current research in toxicology · 2021Article
- In Vitro Effects of Emerging Bisphenols on Myocyte Differentiation and Insulin Responsiveness.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Use of the Adverse Outcome Pathway (AOP) framework to evaluate species concordance and human relevance of Dibutyl phthalate (DBP)-induced male reproductive toxicity.Reproductive toxicology (Elmsford, N.Y.) · 2020Review
- Androgens and the masculinization programming window: human-rodent differences.Biochemical Society transactions · 2020Review
- Application of a combined aggregate exposure pathway and adverse outcome pathway (AEP-AOP) approach to inform a cumulative risk assessment: A case study with phthalates.Toxicology in vitro : an international journal published in association with BIBRA · 2020Article
- Article
- All-trans Retinoic Acid Disrupts Development in Ex Vivo Cultured Fetal Rat Testes. II: Modulation of Mono-(2-ethylhexyl) Phthalate Toxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Validation of an automated counting procedure for phthalate-induced testicular multinucleated germ cells.Toxicology letters · 2018Article
- Perspective: A Neuro-Hormonal Systems Approach to Understanding the Complexity of Cryptorchidism Susceptibility.Frontiers in endocrinology · 2018Article
- From the Cover: Teratogenic Effects of in Utero Exposure to Di-(2-Ethylhexyl)-Phthalate (DEHP) in B6:129S4 Mice.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundIn utero exposure to endocrine-disrupting chemicals may contribute to testicular dysgenesis syndrome (TDS), a proposed constellation of increasingly common male reproductive tract abnormalities (including hypospadias, cryptorchidism, hypospermatogenesis, and testicular cancer). Male rats exposed in utero to certain phthalate plasticizers exhibit multinucleated germ cell (MNG) induction and suppressed steroidogenic gene expression and testosterone production in the fetal testis, causing TDS-consistent effects of hypospadias and cryptorchidism. Mice exposed to phthalates in utero exhibit MNG induction only. This disparity in response demonstrates a species-specific sensitivity to phthalate-induced suppression of fetal Leydig cell steroidogenesis. Importantly, ex vivo phthalate exposure of the fetal testis does not recapitulate the species-specific endocrine disruption, demonstrating the need for a new bioassay to assess the human response to phthalates.
objectivesIn this study, we aimed to develop and validate a rat and mouse testis xenograft bioassay of phthalate exposure and examine the human fetal testis response.
methodsFetal rat, mouse, and human testes were xenografted into immunodeficient rodent hosts, and hosts were gavaged with a range of phthalate doses over multiple days. Xenografts were harvested and assessed for histopathology and steroidogenic end points.
resultsConsistent with the in utero response, phthalate exposure induced MNG formation in rat and mouse xenografts, but only rats exhibited suppressed steroidogenesis. Across a range of doses, human fetal testis xenografts exhibited MNG induction but were resistant to suppression of steroidogenic gene expression.
conclusionsPhthalate exposure of grafted human fetal testis altered fetal germ cells but did not reduce expression of genes that regulate fetal testosterone biosynthesis.
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