title: Age- and species-dependent infiltration of macrophages into the testis of rats and mice exposed to mono-(2-Ethylhexyl) phthalate (MEHP).
abstract: The mechanism by which noninfectious testicular inflammation results in infertility is poorly understood. Here the infiltration of CD11b+ immunoreactive testicular interstitial cells (neutrophil, macrophages, dendritic cells) in immature (Postnatal Day [PND] 21, 28, and 35) and adult (PND 56) Fischer rats is described at 12, 24, and 48 h after an oral dose of 1 g/kg mono-(2-ethylhexyl) phthalate (MEHP), a well-described Sertoli cell toxicant. Increases of CD11b+ cells are evident 12 h after MEHP exposure in PND 21 and 28 rats. In PND 28 rats, CD11b+ cells remained significantly elevated at 48 h, while in PND 21 rats, it returned to control levels by 24 h. The peak number of CD11b+ cells in PND 35 rat testis is delayed until 24 h, but remains significantly elevated at 48 h. In PND 56 rats, no increase in CD11b+ cells occurs after MEHP exposure. In PND 21, 28, and 35 rats, a significant increase in monocyte chemoattractant protein-1 (MCP-1) by peritubular myoid cells occurs 12 h after MEHP. Interestingly, MEHP treatment of C57BL/6J mice did not incite an infiltration of CD11b+ cells at either PND 21 or 28. The peak level of germ cell apoptosis observed 24 h after MEHP exposure in young rats is not seen in mice at any age or in PND 56 rats. Taken together, these findings implicate MCP-1 released by peritubular myoid cells in provoking the migration of CD11b+ cells into the immature rat testis early after MEHP exposure and point to a role for CD11b+ cells in triggering germ cell apoptosis in an age- and species-dependent manner.
authors.affiliation: Center for Molecular and Cellular Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas.
authors.forename: Caitlin J
authors.initials: CJ
authors.lastname: Murphy
authors.affiliation: Center for Molecular and Cellular Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas.
authors.forename: Angela R
authors.initials: AR
authors.lastname: Stermer
authors.affiliation: Center for Molecular and Cellular Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas john.richburg@austin.utexas.edu.
authors.forename: John H
authors.initials: JH
authors.lastname: Richburg
mesh_terms: D000367:Age Factors; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D018932:Chemokine CCL2 / Q000378:metabolism; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D051381:Rats; D012708:Sertoli Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013045:Species Specificity; D013737:Testis / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D004051:Diethylhexyl Phthalate; C016599:mono-(2-ethylhexyl)phthalate
keywords: interstitial cells; macrophage; myoid cells; reproductive immunology; toxicology