ArticleToxicology in vitro : an international journal published in association with BIBRA2016
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.
Article in Toxicology in vitro : an international journal published in association with BIBRA, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 28 citations in OpenAlex.
- In vitro models of the male reproductive system: applications for developmental and reproductive toxicology.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- In Vitro and In Vivo Models for Drug Transport Across the Blood-Testis Barrier.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Do macrophages play a role in the adverse effects of endocrine disrupting chemicals (EDCs) on testicular functions?Frontiers in toxicology · 2023Review
- Maternal and Offspring Sugar Consumption Increases Perigonadal Adipose Tissue Hypertrophy and Negatively Affects the Testis Histological Organization in Adult Rats.Frontiers in cell and developmental biology · 2022Article
- The effects of gene × environment interactions on silver nanoparticle toxicity in the respiratory system: An adverse outcome pathway.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2021Review
- Elevated CCL2 causes Leydig cell malfunction in metabolic syndrome.JCI insight · 2020Article
- In-vitro spermatogenesis through testis modelling: Toward the generation of testicular organoids.Andrology · 2020Review
- Proposed Key Characteristics of Male Reproductive Toxicants as an Approach for Organizing and Evaluating Mechanistic Evidence in Human Health Hazard Assessments.Environmental health perspectives · 2019Article
- MEHP-induced rat testicular inflammation does not exacerbate germ cell apoptosis.Reproduction (Cambridge, England) · 2018Article
- Architecture in 3D cell culture: An essential feature for in vitro toxicology.Toxicology in vitro : an international journal published in association with BIBRA · 2017Review
- Effect of prenatal DINCH plasticizer exposure on rat offspring testicular function and metabolism.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Our 3-dimensional testis co-culture system (3D-TCS) represents a promising model of male reproductive toxicity which captures sensitive processes of male reproductive development and contains the main testes cell types (germ, Leydig and Sertoli cells). Macrophages are another cell type important for testicular function and help to modulate immuno-endocrine processes during testes development. Chemicals such as phthalate esters (PE's) affect macrophage function and testosterone production in the testes in vivo. The aim of this study was to determine whether macrophages were present in the 3D-TCS and investigate responses in our model that may be related to immuno-endocrine functions. We observed consistent expression of the resident macrophage marker ED2 as well as increases in inflammatory cytokines produced by macrophages and testes cells (IL-6, TNF-α and KC/GRO) after exposure to toxic PE's. Pathway analysis of gene expression changes after exposure to PE's showed that IL-6 and TNF-α signaling pathways were enriched after treatment with reproductively toxic, but not non-reproductively toxic phthalates. These results indicate that macrophages and inflammatory processes are captured in the 3D-TCS and that these processes are impacted by exposure to reproductive toxicants. These processes represent a major mode of action for in vivo testis toxicity for a variety of compounds and our novel in vitro model is able to capture toxicant perturbation of immune function.
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Registered trials
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