Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
Address for correspondence: Sherry E. Rier, Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, B-1100 Medical Center North, Nashville, TN 37232. Voice: 615-322-4196; fax: 615-343-7913.
sherry.rier{at}mcmail.vanderbilt.edu
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 (TNF
) 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 TNF
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.
