The potential role of exposure to environmental toxicants in the pathophysiology of endometriosis.

Abstract

Humans and animals are exposed daily to a complex mixture of polyhalogenated aromatic hydrocarbons (PHAHs). Previous work has shown that exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with a dose-dependent increase in the incidence and severity of endometriosis in the rhesus monkey. Dioxin-like chemicals can also exert effects in combination with TCDD via the aryl hydrocarbon receptor. Using a rhesus model of chronic TCDD exposure and endometriosis, serum concentrations of TCDD and 19 dioxin-like PHAHs were quantified 13 years after termination of exposure to TCDD. In additional studies, the immune status of TCDD-exposed monkeys was evaluated. For TCDD-exposed and unexposed animals, TCDD exposure correlated with an increased serum TCDD concentration. Furthermore, TCDD exposure and an elevated serum TCDD concentration were associated with increased serum levels of triglycerides, 1,2,3,6,7,8-hexachlorodibenzofuran (HxCDF), PCB77, and PCB126. Importantly, the animals with elevated serum levels of PCB77 and PCB126 and increased total serum TCDD equivalents (TEQs) had a high prevalence of endometriosis, and the severity of disease correlated with the serum concentration of PCB77. In immune studies, TCDD exposure correlated with increased tumor necrosis factor alpha (TNFalpha) production by peripheral blood mononuclear cells (PBMC) in response to stimulation by T cell mitogen and decreased NK cytolytic activity. Elevated serum concentrations of TCDD, 1,2,3,6,7,8-HxCDF, and PCB126 correlated with increased numbers of CD3+/CD25- and CD3-/CD25+ leukocytes and enhanced secretion of TNFalpha by mitogen-stimulated PBMC. This evidence suggests that TCDD exposure and endometriosis in the rhesus monkey may be associated with increased serum concentrations of specific coplanar PCB compounds and long-term alterations in systemic immunity. Furthermore, the data suggest a potential involvement of an increased body burden of PCB compounds in the etiology of endometriosis in the rhesus. Recent advances in the detection and assay of individual PHAH congeners in biological samples have made it possible to assess total PHAH body burden in humans and animals. Future studies are expected to exploit this advance to assess the health impact of PHAH body burdens in both exposed individuals and the general population. Serum PHAH concentrations and TEQs in TCDD-exposed monkeys with endometriosis are similar to or lower than blood levels in the general human population; thus, it is important to consider the implications of these findings for human health and the prevalence of endometriosis in humans. Additional studies are warranted, particularly in human subjects, to explore the potential implications of these data.