Maternal exposures to endocrine disrupting chemicals and hypospadias in offspring
ABSTRACT Prenatal exposures to endocrine-disrupting chemicals (EDCs) are suspected risk factors in the etiology of hypospadias. The aim of this case-control study was to test the hypothesis of an association between maternal environmental exposures to EDCs and hypospadias in the offspring.
Detailed questionnaire data on occupational and dietary exposures to EDCs in the perinatal period were collected from 80 mothers with hypospadiac infants and from 80 mothers with healthy controls within 24 months of childbirth. Maternal exposure to selected EDCs was also ascertained by measuring the concentration of dichlorodiphenyldichloroethylene, hexachlorobenzene, and several polychlorinated biphenyl congeners in the serum of primiparous mothers of 37 cases and 21 controls.
The risk to bear an hypospadiac infant was associated with perinatal maternal occupational exposures to EDCs evaluated by a job-exposure matrix: jobs with exposure to one class of EDCs (odds ratios [OR](crude), 2.83; 95% confidence intervals [CI], 1.32-6.07; OR(adjusted), 2.44; 95% CI, 1.06-5.61) and jobs with exposure to more than one group of EDCs (OR(crude), 4.27; 95% CI, 1.43-12.78; OR(adjusted), 4.11; 95%CI, 1.34-12.59). Increase in risk was also found among mothers consuming a diet rich in fish or shellfish (OR(crude), 3.41; 95% CI, 1.42-8.23; OR(adjusted), 2.73; 95%CI, 1.09-6.82). Serum hexachlorobenzene concentration above the median of all subjects was significantly associated with the risk of hypospadias (OR(adjusted), 5.50; 95% CI, 1.24-24.31).
This study, although based on a limited number of cases, for the first time provides evidence of an association between maternal exposure to EDCs, in particular elevated plasma hexachlorobenzene concentration, and the development of hypospadias in the offspring.
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ABSTRACT: This review evaluates current knowledge related to trends in the prevalence of hypospadias, the association of hypospadias with endocrine-disrupting exposures, and the potential contribution of genetic susceptibility to its etiology. The review focuses on epidemiologic evidence. Increasing prevalence of hypospadias has been observed, but such increases tend to be localized to specific regions or time periods. Thus, generalized statements that hypospadias is increasing are unsupported. Owing to the limitations of study designs and inconsistent results, firm conclusions cannot be made regarding the association of endocrine-disrupting exposures with hypospadias. Studies with more rigorous study designs (e.g., larger and more detailed phenotypes) and exposure assessment that encompasses more breadth and depth (e.g., specific endocrine-related chemicals) will be critical to make better inferences about these important environmental exposures. Many candidate genes for hypospadias have been identified, but few of them have been examined to an extent that enables solid conclusions. Further study is needed that includes larger sample sizes, comparison groups that are more representative of the populations from which the cases were derived, phenotype-specific analyses, and more extensive exploration of variants. In conclusion, examining the associations of environmental and genetic factors with hypospadias remain important areas of inquiry, although our actual understanding of their contribution to hypospadias risk in humans is currently limited.Birth Defects Research Part A Clinical and Molecular Teratology 07/2012; 94(7):499-510. DOI:10.1002/bdra.23021 · 2.21 Impact Factor
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ABSTRACT: Cryptorchidism, hypospadias, subfertility and testicular germ-cell tumour have been suggested to comprise a testicular dysgenesis syndrome (TDS) based on the premise that each may derive from perturbations of embryonal programming and gonadal development during foetal life. Endocrine-disrupting chemicals have been hypothesized to be associated with these disorders, given the importance of sex steroid hormones in urogenital development and homeostasis. Organochlorines are one such set of compounds which are defined as containing between one and ten covalently bonded chlorine atoms. These compounds are persistent pollutants with long half-lives, accumulate in adipose tissue when ingested, bioaccumulate and biomagnify, and have complex and variable toxicological profiles. Examples of organochlorines include dichloro-diphenyl-trichloroethane and its metabolites, polychlorinated biphenyls, and chlordane. In this comprehensive review of human epidemiologic studies which have tested for associations between organochlorines and facets of TDS, we find evidence for associations between the exposures p,p'-DDE, cis-nonachlor and trans-nonachlor with testicular germ-cell tumour. The sum of the evidence from human epidemiological studies does not indicate any association between specific organochlorines studied and cryptorchidism, hypospadias or fertility. Many other endocrine-disrupting chemicals, including additional organochlorines, have yet to be assessed in relation to disorders associated with TDS, yet study of such chemicals has strong scientific merit given the relevance of such hypotheses to urogenital development.International Journal of Andrology 06/2011; 34(4 Pt 2):e68-84; discussion e84-5. DOI:10.1111/j.1365-2605.2011.01171.x · 3.21 Impact Factor
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ABSTRACT: OBJECTIVES: Pregnant hairdressers may be exposed to a mixture of chemicals in their working environment. The possible relationship between these chemical agents and male reproductive tract malformations has raised concern that the working environment of hairdressers might have adverse effects on fetal development. This study assessed the risk of cryptorchidism and hypospadias among boys of maternal hairdressers. METHODS: National population-based registers were used to determine maternal occupation and identify cases of cryptorchidism and hypospadias. The cohort comprised all children born in Denmark from 1980-2007. Using Cox regression, we estimated hazard ratios (HR) with 95% confidence intervals (95% CI) for hospitalization for cryptorchidism and hypospadias from 1980-2009. RESULTS: Boys of hairdressers were not at increased risk of cryptorchidism (134 cases, HR 0.91; 95% CI 0.77-1.08) or hypospadias (33 cases, HR 1.27; 95% CI 0.90-1.79) compared to children of mothers in other occupations (14 988 and 2556 cases of cryptorchidism and hypospadias, respectively). Additional analyses using children of shop assistants and receptionists as controls and restricted to (i) firstborns, (ii) cryptorchidism cases with corrective surgery, (iii) specific birth years, and (iv) women without social benefit payments in gestational weeks 8-14 produced consistent results of no increased risk. CONCLUSION: Our nationwide cohort study shows that, despite exposure to a complex chemical milieu, hairdressers do not have an increased risk of having boys with cryptorchidism and hypospadias.Scandinavian Journal of Work, Environment & Health 10/2012; 39(3). DOI:10.5271/sjweh.3330 · 3.10 Impact Factor