ArticleToxicology and applied pharmacology2009
Improving in vitro Sertoli cell/gonocyte co-culture model for assessing male reproductive toxicity: Lessons learned from comparisons of cytotoxicity versus genomic responses to phthalates.
Article in Toxicology and applied pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 47 citations in OpenAlex.
- High-content toxicological profiling of 87 compounds using a 3D mouse mini-testis model: a New Approach Methodology (NAM) for prioritizing male reproductive toxicants.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Characterization of primary canine Sertoli cells as a model to test male reproductive toxicant.Toxicology in vitro : an international journal published in association with BIBRA · 2022Article
- Male Infertility in the XXI Century: Are Obesogens to Blame?International journal of molecular sciences · 2022Review
- Article
- 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
- In-vitro spermatogenesis through testis modelling: Toward the generation of testicular organoids.Andrology · 2020Review
- 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
- Evaluation of Culture Time and Media in an In Vitro Testis Organ Culture System.Birth defects research · 2017Article
- High-Content Analysis Provides Mechanistic Insights into the Testicular Toxicity of Bisphenol A and Selected Analogues in Mouse Spermatogonial Cells.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- Is toxicant-induced Sertoli cell injury in vitro a useful model to study molecular mechanisms in spermatogenesis?Seminars in cell & developmental biology · 2016Review
- The presence of macrophages and inflammatory responses in an in vitro testicular co-culture model of male reproductive development enhance relevance to in vivo conditions.Toxicology in vitro : an international journal published in association with BIBRA · 2016Article
- Phthalate metabolism and kinetics in an in vitro model of testis development.Toxicology in vitro : an international journal published in association with BIBRA · 2016Article
- Comparison of toxicogenomic responses to phthalate ester exposure in an organotypic testis co-culture model and responses observed in vivo.Reproductive toxicology (Elmsford, N.Y.) · 2015Article
- Stage-specific signaling pathways during murine testis development and spermatogenesis: A pathway-based analysis to quantify developmental dynamics.Reproductive toxicology (Elmsford, N.Y.) · 2015Article
- Article
- Preparation of rodent testis co-cultures.Current protocols in toxicology · 2013Article
- The blood-testis barrier and its implications for male contraception.Pharmacological reviews · 2012Review
- Cadmium induced p53-dependent activation of stress signaling, accumulation of ubiquitinated proteins, and apoptosis in mouse embryonic fibroblast cells.Toxicological sciences : an official journal of the Society of Toxicology · 2011Article
- The role of molecular biology in the biomonitoring of human exposure to chemicals.International journal of molecular sciences · 2010Review
- Methylmercury induced toxicogenomic response in C57 and SWV mouse embryos undergoing neural tube closure.Reproductive toxicology (Elmsford, N.Y.) · 2010Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Gonocytes exist in the neonatal testis and represent a transient population of male germ-line stem cells. It has been shown that stem cell self-renewal and progeny production is probably controlled by the neighboring differentiated cells and extracellular matrix (ECM) in vivo known as niches. Recently, we developed an in vitro three-dimensional (3D) Sertoli cell/gonocyte co-culture (SGC) model with ECM overlay, which creates an in vivo-like niche and supports germ-line stem cell functioning within a 3D environment. In this study, we applied morphological and cytotoxicity evaluations, as well as microarray-based gene expression to examine the effects of different phthalate esters (PE) on this model. Known in vivo male developmentally toxic PEs (DTPE) and developmentally non-toxic PEs (DNTPE) were evaluated. We observed that DTPE induced significantly greater dose-dependent morphological changes, a decrease in cell viability and an increase in cytotoxicity compared to those treated with DNTPE. Moreover, the gene expression was more greatly altered by DTPE than by DNTPE and non-supervised cluster analysis allowed the discrimination of DTPE from the DNTPE. Our systems-based GO-Quant analysis showed significant alterations in the gene pathways involved in cell cycle, phosphate transport and apoptosis regulation with DTPE but not with DNTPE treatment. Disruptions of steroidogenesis related-gene expression such as Star, Cyp19a1, Hsd17b8, and Nr4a3 were observed in the DTPE group, but not in the DNTPE group. In summary, our observation on cell viability, cytotoxicity, and microarray-based gene expression analysis induced by PEs demonstrate that our in vitro 3D-SGC system mimicked in vivo responses for PEs and suggests that the 3D-SGC system might be useful in identifying developmental reproductive toxicants.
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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.