Menstrual cycle characteristics and reproductive hormone levels in women exposed to atrazine in drinking water

Department of Environmental and Radiological Health Sciences, 1681 Campus Delivery, Colorado State University, Fort Collins, CO 80523-1681, USA.
Environmental Research (Impact Factor: 4.37). 11/2011; 111(8):1293-301. DOI: 10.1016/j.envres.2011.09.009
Source: PubMed


Atrazine is the most commonly used herbicide in the U.S. and a wide-spread groundwater contaminant. Epidemiologic and laboratory evidence exists that atrazine disrupts reproductive health and hormone secretion. We examined the relationship between exposure to atrazine in drinking water and menstrual cycle function including reproductive hormone levels. Women 18-40 years old residing in agricultural communities where atrazine is used extensively (Illinois) and sparingly (Vermont) answered a questionnaire (n=102), maintained menstrual cycle diaries (n=67), and provided daily urine samples for analyses of luteinizing hormone (LH), and estradiol and progesterone metabolites (n=35). Markers of exposures included state of residence, atrazine and chlorotriazine concentrations in tap water, municipal water and urine, and estimated dose from water consumption. Women who lived in Illinois were more likely to report menstrual cycle length irregularity (odds ratio (OR)=4.69; 95% confidence interval (CI): 1.58-13.95) and more than 6 weeks between periods (OR=6.16; 95% CI: 1.29-29.38) than those who lived in Vermont. Consumption of >2 cups of unfiltered Illinois water daily was associated with increased risk of irregular periods (OR=5.73; 95% CI: 1.58-20.77). Estimated "dose" of atrazine and chlorotriazine from tap water was inversely related to mean mid-luteal estradiol metabolite. Atrazine "dose" from municipal concentrations was directly related to follicular phase length and inversely related to mean mid-luteal progesterone metabolite levels. We present preliminary evidence that atrazine exposure, at levels below the US EPA MCL, is associated with increased menstrual cycle irregularity, longer follicular phases, and decreased levels of menstrual cycle endocrine biomarkers of infertile ovulatory cycles.

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    • "There are several studies in recent years investigating the impacts of atrazine exposure on human health with evidence suggesting weak correlations as well as several suggesting links to adverse health effects including adverse birth outcomes, endocrine disruption, and carcinogenesis (Cragin et al. 2011; Freeman et al. 2011; Rinsky et al. 2012). In addition to human studies, numerous animal studies aimed at identifying mode(s) of action through which atrazine exerts its effects have been completed. "
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    ABSTRACT: Atrazine is an herbicide applied to agricultural crops and is indicated to be an endocrine disruptor. Atrazine is frequently found to contaminate potable water supplies above the maximum contaminant level of 3μg/L as defined by the U. S. Environmental Protection Agency. The developmental origin of adult disease hypothesis suggests that toxicant exposure during development can increase the risk of certain diseases during adulthood. However, the molecular mechanisms underlying disease progression are still unknown. In this study, zebrafish embryos were exposed to 0, 0.3, 3, or 30μg/L atrazine throughout embryogenesis. Larvae were then allowed to mature under normal laboratory conditions with no further chemical treatment until 7 days post fertilization (dpf) or adulthood and neurotransmitter analysis completed. No significant alterations in neurotransmitter levels was observed at 7 dpf or in adult males, but a significant decrease in 5-Hydroxyindoleacetic acid (5-HIAA) and serotonin turnover was seen in adult female brain tissue. Transcriptomic analysis was completed on adult female brain tissue to identify molecular pathways underlying the observed neurological alterations. Altered expression of 1853, 84, and 419 genes in the females exposed to 0.3, 3, or 30μg/L atrazine during embryogenesis were identified, respectively. There was a high level of overlap between the biological processes and molecular pathways in which the altered genes were associated. Moreover, a subset of genes was down regulated throughout the serotonergic pathway. These results provide support of the developmental origins of neurological alterations observed in adult female zebrafish exposed to atrazine during embryogenesis. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Toxicology 04/2015; 333. DOI:10.1016/j.tox.2015.04.016 · 3.62 Impact Factor
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    • "ATZ has a lot of adverse effect on health such as tumors, breast, ovarian, and uterine cancers as well as leukemia and lymphoma. It is an endocrine disrupting chemical interrupting regular hormone function and alters reproductive function not only in human [10], but also in many other species such as developing alligators [11], birds [12], goat [13], and as most vulnerable amphibians [14] [15] and fish [16], causing birth defects, reproductive tumors, and weight loss in amphibians as well as humans. It also causes induction of the detoxifying hepatic microsomal oxidative enzymes, continual synthesis of esterases, physiological adaptation to decreased esterase levels, and adaptation of cholinergic receptors [17]. "
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    ABSTRACT: Either during gestation or lactation, the experimental mouse dams received one of the following treatments: (a) diet free of pesticide; (b) diet enriched with atrazine (ATZ); 31.0 μg kg−1; (c) diet free of pesticide + oral vitamin E (α-tocopherol; 200 mg kg−1 per mouse); and (d) diet enriched with ATZ (31.0 μg kg−1) + oral vitamin E (200 mg kg−1 per mouse). At the weaning, pups and dams were killed and selected organs and blood samples were collected for analyses. Compared with the control results, ATZ induced alteration in a number of biochemical and histopathological parameters either in the dams or their offspring. The ameliorative effect of vitamin E, based on estimating the “Ameliorative Index; AI” to malondialdehyde (MDA) and superoxide dismutase (SOD) ranged between 0.95 and 1.06 (≈1.0) for the dams and the pups either in gestational or lactational exposure routes. In general, the mouse pups were more vulnerable to ATZ toxicity than their mothers and exposure during gestation was suggested to be more effective than during lactation. The findings may support the need to further investigating the adverse effects of exposure to low doses of commonly used pesticides, especially during pregnancy and breast-feeding as well as effects on newborn child.
    Toxicology Reports 12/2014; 1:53–68. DOI:10.1016/j.toxrep.2014.04.001
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    • "Regarding its effects on the brain, we and others have shown in rodents that short-term (!25 mg/kg), long-term (10 mg/kg), or perinatal (1.4 mg/kg) ATR exposures alter monoamine-associated behaviors and brain dopamine and serotonin homeostasis, suggesting that, in the brain, ATR targets tyrosine and tryptophan metabolism (Bardullas et al., 2011; Lin et al., 2013a, 2014). In line with the rodent studies, epidemiological data based on low, environmental ATR exposure levels report possible endocrine, i.e., menstrual cycle length irregularity (Cragin et al., 2011), metabolic , i.e., increased risk of gestational diabetes mellitus (Saldana et al., 2007), and neurologic, i.e., increased incidence of Parkinson's disease (PD; Shaw, 2011) perturbations due to ATR. "
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    ABSTRACT: Overexposure to the commonly used herbicide atrazine (ATR) affects several organ systems, including the brain. Previously, we demonstrated that short-term oral ATR exposure causes behavioral deficits and dopaminergic and serotonergic dysfunction in the brains of mice. Using adult male C57BL/6 mice, the present study aimed to investigate effects of a 10-day oral ATR exposure (0, 5, 25, 125, or 250 mg/kg) on the mouse plasma metabolome and to determine metabolic pathways affected by ATR that may be reflective of ATR’s effects on the brain and useful to identify peripheral biomarkers of neurotoxicity. Four hours after the last dosing on day 10, plasma was collected and analyzed with high-performance, dual chromatography-Fourier-transform mass spectrometry that was followed by biostatistical and bioinformatic analyses. ATR exposure (≥5 mg/kg) significantly altered plasma metabolite profile and resulted in a dose-dependent increase in the number of metabolites with ion intensities significantly different from the control group. Pathway analyses revealed that ATR exposure strongly correlated with and disrupted multiple metabolic pathways. Tyrosine, tryptophan, linoleic acid and α-linolenic acid metabolic pathways were among the affected pathways, with α-linolenic acid metabolism being affected to the greatest extent. Observed effects of ATR on plasma tyrosine and tryptophan metabolism may be reflective of the previously reported perturbations of brain dopamine and serotonin homeostasis, respectively. ATR-caused alterations in the plasma profile of α-linolenic acid metabolism are a potential novel and sensitive plasma biomarker of ATR effect and plasma metabolomics could be used to better assess the risks, including to the brain, associated with ATR overexposure.
    Toxicology 11/2014; 326. DOI:10.1016/j.tox.2014.11.001 · 3.62 Impact Factor
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