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Title: Mono-(2-ethylhexyl) phthalate-induced Sertoli cell injury stimulates the production of pro-inflammatory cytokines in Fischer 344 rats.

Authors: Stermer, Angela R; Murphy, Caitlin J; Ghaffari, Rashin; Di Bona, Kristin R; Voss, Jorine J; Richburg, John H

Published In Reprod Toxicol, (2017 04)

Abstract: Exposure of rodents to the Sertoli cell (SC) toxicant mono-(2-ethylhexyl) phthalate (MEHP) has been reported to trigger an infiltration of macrophages into the testis in an age- and species-dependent manner. Here we challenge the hypothesis that the peripubertal rat-specific infiltration of macrophages after MEHP exposure is due, in part, to an increase in SC-specific inflammatory cytokine expression. To rule out that germ cell(GC) apoptosis itself is responsible for macrophage recruitment, rats were exposed to a direct GC toxicant, methoxyacetic acid (MAA), but no infiltration of macrophages was observed. Next, mRNA levels of inflammatory cytokines were evaluated after MEHP exposure. IL-1α, IL-6, and MCP-1 expression were increased in vivo and correlated with macrophage infiltration in a species-specific manner. Additionally, IL-6 and MCP-1 expression was increased in SC-GC co-cultures and ASC-17D SCs. These results indicate that MEHP-injury in pubertal rats specifically stimulates secretion of pro-inflammatory cytokines and alters the immune microenvironment.

PubMed ID: 28238932 Exiting the NIEHS site

MeSH Terms: Acetates/toxicity; Animals; Apoptosis/drug effects; Cell Line; Cells, Cultured; Cytokines/genetics*; Diethylhexyl Phthalate/analogs & derivatives*; Diethylhexyl Phthalate/toxicity; Endocrine Disruptors/toxicity*; Macrophages/drug effects; Male; Mice, Inbred C57BL; RNA, Messenger/metabolism; Rats, Inbred F344; Sertoli Cells/drug effects*; Sertoli Cells/immunology; Species Specificity

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