Over the last few decades, concern has heightened over the potential hormone-like effects of environmental chemicals on the reproductive health of fish, wildlife, and humans. The compound 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environmental contaminant, produced by various chemical reactions and combustion processes, including waste incineration, and has been shown in animals to be a potent endocrine disruptor. On July 10,1976, as a result of a chemical explosion, residents of Seveso, Italy experienced the highest levels of TCDD exposure in a human population. We followed up the women 20 years after the accident to determine whether they were at higher risk for reproductive disease. Women aged 0 to 40 years at the time of the explosion, and who lived in Zones A or B were interviewed extensively about their reproductive and pregnancy histories; had a blood draw, pelvic exam, and transvaginal ultrasound; and were asked to complete a menstrual diary. Serum specimens stored from the time of the explosion were analyzed to determine individual levels of TCDD exposure. The Seveso Women's Health Study, originally funded in 1996 (R01 ES07171) aimed to examine the relationship of serum TCDD levels and endometriosis. Continued funding in 1999 allowed the analysis of additional serum specimens for TCDD and examination of the relation to other reproductive endpoints: menstrual cycle characteristics, age of menarche, fetal loss and birthweight, age at menopause, and breast cancer incidence. The present application focuses on the health and function of the ovaries, uterus, and breast in order to document the substantial evidence in animals. Specifically, we aim to determine the relation of serum TCDD levels to fertility (time to conception and clinical infertility); ovarian function (number of ovarian follicles, presence of functional ovarian cysts, serum hormone levels); uterine health (uterine volume, endometrial thickness, and the occurrence/number of fibroids); the occurrence of benign breast disease, and the initiation/duration of lactation. We also will examine whether the above relationships are modified by developmental status (i.e., pre- or post-menarche) at the time of TCDD exposure. The Seveso Women's Health Study is the only comprehensive study to date of the reproductive health of a human female population exposed to TCDD. This study has the benefit of being a large cohort study with a wide range of TCDD exposure, documented by individual-level TCDD measured in sera collected soon after the explosion.
| Eskenazi, Brenda; Warner, Marcella; Brambilla, Paolo et al. (2018) The Seveso accident: A look at 40?years of health research and beyond. Environ Int 121:71-84 |
| Ames, Jennifer; Warner, Marcella; Brambilla, Paolo et al. (2018) Neurocognitive and physical functioning in the Seveso Women's Health Study. Environ Res 162:55-62 |
| Ye, Morgan; Warner, Marcella; Mocarelli, Paolo et al. (2018) Prenatal exposure to TCDD and atopic conditions in the Seveso second generation: a prospective cohort study. Environ Health 17:22 |
| Emond, C; DeVito, M; Warner, M et al. (2016) An assessment of dioxin exposure across gestation and lactation using a PBPK model and new data from Seveso. Environ Int 92-93:23-32 |
| Eskenazi, Brenda; Warner, Marcella; Sirtori, Marcella et al. (2014) Serum dioxin concentrations and bone density and structure in the Seveso Women's Health Study. Environ Health Perspect 122:51-7 |
| Chevrier, Jonathan; Warner, Marcella; Gunier, Robert B et al. (2014) Serum dioxin concentrations and thyroid hormone levels in the Seveso Women's Health Study. Am J Epidemiol 180:490-8 |
| Warner, Marcella; Mocarelli, Paolo; Brambilla, Paolo et al. (2014) Serum TCDD and TEQ concentrations among Seveso women, 20 years after the explosion. J Expo Sci Environ Epidemiol 24:588-94 |
| Wesselink, Amelia; Warner, Marcella; Samuels, Steven et al. (2014) Maternal dioxin exposure and pregnancy outcomes over 30 years of follow-up in Seveso. Environ Int 63:143-8 |
| Warner, Marcella; Mocarelli, Paolo; Brambilla, Paolo et al. (2013) Diabetes, metabolic syndrome, and obesity in relation to serum dioxin concentrations: the Seveso women's health study. Environ Health Perspect 121:906-11 |
| Warner, Marcella; Mocarelli, Paolo; Samuels, Steven et al. (2011) Dioxin exposure and cancer risk in the Seveso Women's Health Study. Environ Health Perspect 119:1700-5 |
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