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Endocrine Disruptors Research
Research Results: Human Health Effects
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Dioxin and Steroid Regulation in an Endometriosis Model
Kevin G. Osteen – Vanderbilt University School of Medicine, Nashville, TN
EPA STAR Grant #R826300
- The expression of matrix metalloproteinases (MMPs) was increased in endometriosis tissues, and is similar to observations in normal endometria that have been treated in vivo with TCDD.
- TCDD was found to prevent progesterone’s normal suppression of MMP activity by blocking its ability to up-regulate TGF- b 2 expression.
- TCDD disrupts the expression of the progesterone receptor isoforms A and B (PR-A, PR-B), resulting in a decreased PR-B/PR-A ratio. This is significant because a decreased PR ratio (increased PR-A; decreased PR-B) has been associated with both endometriosis and in vitro TCDD exposure.
- This grant demonstrated the benefits of an endometriosis model involving the ectopic implantation of human endometrial tissue in nude mice.
More information (PDF, 3 pp, 88 K, about PDF)
Dioxins, Male Pubertal Development and Testis Function
Russ Hauser - Harvard School of Public Health
EPA STAR Grant #R829437
- This grant is funding a study of potential growth and reproductive impacts of dioxin exposure in a cohort of 8-9 year-old Russian boys exposed to dioxins from a chemical plant. A previous pilot study indicated that in the town of Chapaevsk, where a documented high exposure to dioxins exist due to a chemical-industrial complex, boys are thinner than both U.S. and Russian boys in general, and Chapaevsk boys have a later onset of puberty and attainment of sexual maturity than boys from other countries.
- In further analysis under this grant of a subset of the pilot study cohort, older age and consumption of local meats and fish were found to be predictors of the sum of dioxins in the boys' serum. There also was a suggestive, though non-significant, inverse association between current residential distance to the chemical plant and total dioxin levels in blood samples. There was no difference in dioxin levels between the groups of boys with congenital abnormalities and the control boys (though the small size of the study limits its power to detect differences).
- The main study being funded under this grant will monitor the growth, sexual maturation, and reproductive hormone levels in 500 8- and 9-year old Chapaevsk boys, and characterize adverse effects associated with dioxin exposures.
More information (PDF, 3 pp, 37 K, about PDF)
Endocrine Disrupting Chemicals and Thyroid Outcomes
Henry Anderson – Wisconsin Department of Health & Family Services
EPA STAR Grant #R830254
- Recruitment and data collection are ongoing in this five year epidemiological study.
- The results of this study will investigate whether exposure to PBDEs, PCBs, and DDE resulting from the consumption of sport fish increases the risk of thyroid impairment and diabetes.
- The results will provide information about the impact of the flame retardant, PBDE, on thyroid function and diabetes.
More information(PDF, 4 pp, 34 K, about PDF)
Latent Effects of Gestational Exposure to Heptachlor
Dean Baker - University of California - Irvine
EPA STAR Grant #R829439
- This study is funding the third phase of an epidemiological study of a group of young adults exposed to heptachlor epoxide in utero. Reproductive and immunological function are being evaluated. Recruitment and data collection are ongoing.
- Initial analysis of the reproductive and immune function studies in the subjects recruited thus far has found hormonal indications of slightly delayed sexual maturity indicators and shorter menstruation, correlated with the amount of heptachlor-contaminated milk ingested by the mothers.
- Initial analysis of the reproductive and immune function studies in the subjects recruited thus far has found hormonal indications of slightly delayed sexual maturity indicators and shorter menstruation, correlated with the amount of heptachlor-contaminated milk ingested by the mothers.
- Study findings thus far have been limited by small sample size, incomplete followup, and lack of precise exposure data.
More information (PDF, 2 pp, 35 K, about PDF)
Persistent Organic Pollutants and Endometriosis Risk
Victoria Holt – Fred Hutchinson Cancer Research Center
EPA STAR Grant #R829438
- The purpose of the study was to investigate the relationship between endometriosis and exposure to organochlorine compounds (including the pesticide methoxychlor) and polychlorinated biphenyls in a large population-based study, and determine whether these associations are modified by polymorphisms in genes involved in chemical detoxification and estrogen metabolism.
- Analyses of blood and urine samples for PCBs, pesticides, and metabolites, as well as genotyping of subjects for GSTM1 and COMT polymorphisms, are ongoing.
- No association has been found between self-reported exposure to all pesticides combined and endometriosis risk (Odds Ratio [OR]=0.96, 95% Confidence Interval [CI]=0.70-1.33); however, exposure to herbicides and fungicides appeared to increase disease risk.
- There was little apparent modification of these risks by the genetic polymorphisms so far evaluated.
- The effect of serum levels of several organic pollutants on endometriosis risk will be evaluated.
- The results of this study will indicate whether exposure to organochlorine compounds and polychlorinated biphenyls increases endometriosis risk and whether the risk is modified by genetic polymorphisms.
More information (PDF, 2 pp, 81 K, about PDF)
Study of Phthalates in Pregnant Woman and Children
Shanna H. Swan - University of Missouri - Columbia
EPA STAR Grant #R829436
- This grant has funded preliminary analyses in a major investigation of the relationship between phthalate levels in urine, indices of household exposure, and reproductive outcomes in a large cohort of pregnant women
- Of the nine phthalates assayed in maternal urine samples, all were found above the limit of detection in at least 50 percent of prenatal samples, and five metabolites were found in almost all (over 90%) of the samples.
- Urine concentrations of phthalate metabolites exhibited geographic variability, with higher exposures possibly correlated with phthalate use in pesticide formulations.
- Metabolite levels in women's samples of three butyl phthalates, but not other phthalates, were significantly and inversely associated with their partners' semen quality.
- This study is the first to obtain urinary phthalate metabolites in samples from mothers (pre- and postnatally) and infants and evaluate concentrations in relation to structural and functional development of the breast and/or genitalia in males and females.
More information (PDF, 2 pp, 35 K, about PDF)
The Michigan PBB Cohort 20 Years: Endocrine Disruption?
Michele Marcus - Emory University
EPA STAR Grant #R825300
- This grant supported a major epidemiological investigation of a unique cohort of reproductive age women and their daughters who were exposed to polybrominated biphenyls (PBBs).
- Breastfed daughters exposed to high levels of PBB in utero had an earlier age at menarche than breastfed girls exposed to lower levels of PBB in utero or girls who were not breastfed, even after adjustment for potential confounders.
- Women with high exposures to PBB in serum and who had recently lost weight had shorter menstrual cycles and longer bleed lengths than women whose exposure levels were undetectable in serum and experienced a recent weight loss.
- PBB or PCB exposure, measured upon enrollment, is not associated with time to menopause, uterine fibroids, risk of endometriosis, or self-reported physician-diagnosed benign breast disease among women followed for over 20 years.
- The associations observed here support the hypothesis that pubertal events and menstrual cycle characteristics may be affected by pre- and postnatal exposure to organohalogens.
More information (PDF, 5 pp, 94 K, about PDF)