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

• DOI: 10.1016/j.reprotox.2017.02.013
• Publication Date: 2017-02-24T09:46:28Z
• Authors: Angela R. Stermer; Caitlin J. Murphy; Rashin Ghaffari; Kristin R. Di Bona; Jorine J. Voss; John H. Richburg
• Keywords: Male; 0301 basic medicine; Sertoli Cells; Macrophages; Apoptosis; Acetates; Endocrine Disruptors; Toxicology; Rats, Inbred F344; Cell Line; Mice, Inbred C57BL; 03 medical and health sciences; Species Specificity; Diethylhexyl Phthalate; Animals; Cytokines; RNA, Messenger; Cells, Cultured

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.