ArticleEnvironmental health perspectives2016
Systems Toxicology of Male Reproductive Development: Profiling 774 Chemicals for Molecular Targets and Adverse Outcomes.
Article in Environmental health perspectives, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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.
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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.
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Who cites it
21 citing papers in PubMed, 52 citations in OpenAlex.
- Environmental oestrogens disrupt testicular descent and damage male reproductive health: Mechanistic insight.Journal of cellular and molecular medicine · 2023Review
- High-content analysis of testicular toxicity of BPA and its selected analogs in mouse spermatogonial, Sertoli cells, and Leydig cells revealed BPAF induced unique multinucleation phenotype associated with the increased DNA synthesis.Toxicology in vitro : an international journal published in association with BIBRA · 2023Article
- Review
- Predicting Prenatal Developmental Toxicity Based On the Combination of Chemical Structures and Biological Data.Environmental science & technology · 2022Article
- Emerging concepts and opportunities for endocrine disruptor screening of the non-EATS modalities.Environmental research · 2022Article
- 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
- Retinoid signaling in skeletal development: Scoping the system for predictive toxicology.Reproductive toxicology (Elmsford, N.Y.) · 2021Review
- Meeting report on the NIDDK/AUA Workshop on Congenital Anomalies of External Genitalia: challenges and opportunities for translational research.Journal of pediatric urology · 2020Review
- Profiling the ToxCast Library With a Pluripotent Human (H9) Stem Cell Line-Based Biomarker Assay for Developmental Toxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Characterizing cleft palate toxicants using ToxCast data, chemical structure, and the biomedical literature.Birth defects research · 2020Article
- Mitochondria as a target of organophosphate and carbamate pesticides: Revisiting common mechanisms of action with new approach methodologies.Reproductive toxicology (Elmsford, N.Y.) · 2019Article
- Linking Bisphenol S to Adverse Outcome Pathways Using a Combined Text Mining and Systems Biology Approach.Environmental health perspectives · 2019Article
- Identifying Attributes That Influence In Vitro-to-In Vivo Concordance by Comparing In Vitro Tox21 Bioactivity Versus In Vivo DrugMatrix Transcriptomic Responses Across 130 Chemicals.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- A systems biology approach to predictive developmental neurotoxicity of a larvicide used in the prevention of Zika virus transmission.Toxicology and applied pharmacology · 2018Article
- Article
- Blood-brain barrier development: Systems modeling and predictive toxicology.Birth defects research · 2017Review
- Epithelial-mesenchymal transformation and apoptosis in rat urethra development.Pediatric research · 2017Article
- Using exposure prediction tools to link exposure and dosimetry for risk-based decisions: A case study with phthalates.Chemosphere · 2017Article
- From the Cover: An Animal-Free In Vitro Three-Dimensional Testicular Cell Coculture Model for Evaluating Male Reproductive Toxicants.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- Association of Blood and Seminal Plasma Cadmium and Lead Levels With Semen Quality in Non-Occupationally Exposed Infertile Men in Abakaliki, South East Nigeria.Journal of family & reproductive health · 2017Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundTrends in male reproductive health have been reported for increased rates of testicular germ cell tumors, low semen quality, cryptorchidism, and hypospadias, which have been associated with prenatal environmental chemical exposure based on human and animal studies.
objectiveIn the present study we aimed to identify significant correlations between environmental chemicals, molecular targets, and adverse outcomes across a broad chemical landscape with emphasis on developmental toxicity of the male reproductive system.
methodsWe used U.S. EPA's animal study database (ToxRefDB) and a comprehensive literature analysis to identify 774 chemicals that have been evaluated for adverse effects on male reproductive parameters, and then used U.S. EPA's in vitro high-throughput screening (HTS) database (ToxCastDB) to profile their bioactivity across approximately 800 molecular and cellular features.
resultsA phenotypic hierarchy of testicular atrophy, sperm effects, tumors, and malformations, a composite resembling the human testicular dysgenesis syndrome (TDS) hypothesis, was observed in 281 chemicals. A subset of 54 chemicals with male developmental consequences had in vitro bioactivity on molecular targets that could be condensed into 156 gene annotations in a bipartite network.
conclusionComputational modeling of available in vivo and in vitro data for chemicals that produce adverse effects on male reproductive end points revealed a phenotypic hierarchy across animal studies consistent with the human TDS hypothesis. We confirmed the known role of estrogen and androgen signaling pathways in rodent TDS, and importantly, broadened the list of molecular targets to include retinoic acid signaling, vascular remodeling proteins, G-protein coupled receptors (GPCRs), and cytochrome P450s. CITATION: Leung MC, Phuong J, Baker NC, Sipes NS, Klinefelter GR, Martin MT, McLaurin KW, Setzer RW, Darney SP, Judson RS, Knudsen TB. 2016. Systems toxicology of male reproductive development: profiling 774 chemicals for molecular targets and adverse outcomes. Environ Health Perspect 124:1050-1061; http://dx.doi.org/10.1289/ehp.1510385.
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Registered trials
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.