title: Developmental exposure of mice to TCDD elicits a similar uterine phenotype in adult animals as observed in women with endometriosis.
abstract: Whether environmental toxicants impact an individual woman's risk for developing endometriosis remains uncertain. Although the growth of endometrial glands and stroma at extra-uterine sites is associated with retrograde menstruation, our studies suggest that reduced responsiveness to progesterone may increase the invasive capacity of endometrial tissue in women with endometriosis. Interestingly, our recent studies using isolated human endometrial cells in short-term culture suggest that experimental exposure to the environmental contaminant 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD) can alter the expression of progesterone receptor isotypes. Compared to adult exposure, toxicant exposure during development can exert a significantly greater biological impact, potentially affecting the incidence of endometriosis in adults. To address this possibility, we exposed mice to TCDD at critical developmental time points and subsequently examined uterine progesterone receptor expression and steroid responsive transforming growth factor-beta2 expression in adult animals. We find that the uterine phenotype of toxicant-exposed mice is markedly similarly to the endometrial phenotype of women with endometriosis.
authors.affiliation: Women's Reproductive Health Research Center, Department of Obstetrics & Gynecology, Vanderbilt University School of Medicine, 1161 21st Avenue S, MCN B-1100, Nashville, TN 37232, USA.
authors.forename: Tultul
authors.initials: T
authors.lastname: Nayyar
authors.forename: Kaylon L
authors.initials: KL
authors.lastname: Bruner-Tran
authors.forename: Dagmara
authors.initials: D
authors.lastname: Piestrzeniewicz-Ulanska
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Osteen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004195:Disease Models, Animal; D004715:Endometriosis / Q000378:metabolism / Q000473:pathology*; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004785:Environmental Pollutants / Q000506:poisoning*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D010052:Ovariectomy; D000072317:Polychlorinated Dibenzodioxins / Q000506:poisoning*; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000378:metabolism; D012737:Sex Factors; D053781:Transforming Growth Factor beta2 / Q000378:metabolism; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D011980:Receptors, Progesterone; D053781:Transforming Growth Factor beta2; C101118:progesterone receptor A; C097314:progesterone receptor B; D011374:Progesterone; D004958:Estradiol; D019363:Cytochrome P-450 CYP1A1