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.
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.
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DOI：
10.1016/j.tiv.2016.08.003
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发表时间：
2016-10
影响因子：
3.2
通讯作者：
Faustman, Elaine M.
中科院分区：
文献类型：
--
作者：
Harris, Sean;Shubin, Sara Pacheco;Wegner, Susanna;Van Ness, Kirk;Green, Foad;Hong, Sung Woo;Faustman, Elaine M.
我们的 3 维睾丸共培养系统 (3D-TCS) 代表了一种有前途的男性生殖毒性模型，它捕获男性生殖发育的敏感过程，并包含主要的睾丸细胞类型（生殖细胞、间质细胞和支持细胞）。巨噬细胞是另一种对睾丸功能重要的细胞类型，有助于调节睾丸发育过程中的免疫内分泌过程。邻苯二甲酸酯 (PE) 等化学物质会影响体内睾丸中巨噬细胞的功能和睾酮的产生。本研究的目的是确定 3D-TCS 中是否存在巨噬细胞，并研究我们的模型中可能与免疫内分泌功能相关的反应。我们观察到，暴露于有毒 PE 后，常驻巨噬细胞标记物 ED2 的表达一致，以及巨噬细胞和睾丸细胞产生的炎症细胞因子（IL-6、TNF-α 和 KC/GRO）增加。暴露于 PE 后基因表达变化的通路分析表明，用生殖毒性而非非生殖毒性邻苯二甲酸盐处理后，IL-6 和 TNF-α 信号通路得到富集。这些结果表明，3D-TCS 捕获了巨噬细胞和炎症过程，并且这些过程受到生殖毒物暴露的影响。这些过程代表了多种化合物体内睾丸毒性的主要作用模式，我们的新型体外模型能够捕获毒物对免疫功能的扰动。
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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影响因子：
3.3
作者：
Harris, Sean;Hermsen, Sanne A. B.;Yu, Xiaozhong;Hong, Sung Woo;Faustman, Elaine M.
通讯作者：
Faustman, Elaine M.
影响因子：
4
作者：
Buteau-Lozano, Helene;Velasco, Guillaume;Perrot-Applanat, Martine
通讯作者：
Perrot-Applanat, Martine
影响因子：
5.2
作者：
Lhuguenot, Jean-Claude
通讯作者：
Lhuguenot, Jean-Claude
影响因子：
5.8
作者：
Samson, M;Peale, FV;Ferrara, N
通讯作者：
Ferrara, N
影响因子：
10.4
作者：
Goldman, LR;Koduru, S
通讯作者：
Koduru, S