Maternal exposures to endocrine disrupting chemicals and hypospadias in offspring

Department of Animal and Human Biology (c/o Anthropology), University of Rome, La Sapienza, Rome, Italy.
Birth Defects Research Part A Clinical and Molecular Teratology (Impact Factor: 2.09). 04/2010; 88(4):241-50. DOI: 10.1002/bdra.20657
Source: PubMed


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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    • "HCB levels in fatty tissue in children have been associated with cryptorchidism [8], but not when HCB was evaluated in breast milk or maternal blood [9] [10]. Also, hypospadias in sons has been associated with maternal levels of HCB [11], these findings pointing to anti-androgenic in vivo effects at exposure concentrations encountered in the general population. A study from 2013 investigating couple fecundity by time to pregnancy showed a significant negative fecundity odds ratio with serum HCB in females only, but the relation did not persist after adjustment for confounding factors [12]. "
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    ABSTRACT: Hexachlorobenzene (HCB) is a persistent environmental fungicide that may disrupt androgen regulation. The aim of this study was to investigate associations between HCB levels and biomarkers of male reproductive function. 589 spouses of pregnant women from Greenland, Poland and Ukraine were enrolled between 2002 and 2004. The men provided semen and blood samples and were interviewed. HCB was measured in serum by gas chromatography. The mean serum concentrations of HCB were higher in Ukraine (182.3 ng/g lipid) and Greenland (79.0 ng/g lipid) compared to Poland (14.2 ng/g lipid). Sex Hormone Binding Globulin (SHBG) and Free Androgen Index (FAI) were associated with HCB in men from Ukraine and Poland. This study spanning large differences in environmental HCB exposure levels shows a positive association for SHBG and negative association for FAI with high serum levels of HCB in fertile men, but without major consequences for semen quality and the Inuit study population. Copyright © 2015. Published by Elsevier Inc.
    Reproductive Toxicology 07/2015; 58. DOI:10.1016/j.reprotox.2015.07.074 · 3.23 Impact Factor
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    • "Trace amounts of As have been observed in semen which suggests that it may inhibit the function of enzymes present in the acrosome and the membrane which covers the head of the sperm. However, it remains an important issue to corroborate or refute the hypothesis that the role of heavy metals in male reproductive tract disorders [7] [8] [9] [10] [11] [12] [13] [14] [15]. Hence, the present study was designed to investigate the possible association between extent of heavy metal exposure with the etiology of hypospadias with reference to heavy metal levels in blood of boys and their mothers and compare it with that of control cases. "
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    ABSTRACT: Background. Hypospadias is a part of testicular digenesis syndrome (TDS) which includes infertility, cryptorchidism, and spermatogenesis. Heavy metals act as endocrine disrupting compounds. Heavy metals such as cadmium, chromium, arsenic, and lead have been associated with male infertility, cryptorchidism, spermatogenesis, cancer, reproductive disorder, and neurological disorder. However, it remains an important issue to corroborate or refute the hypothesis that the role of heavy metals in male reproductive tract disorders. Hence, the present study was designed to investigate the possible association of heavy metal and risk of hypospadias by estimating the blood heavy metal levels. Methods. In this case control study, 50 hypospadias boys diagnosed and confirmed by a pediatric urologist and 50 randomly selected age-matched (1-5 years) healthy control boys not suffering from any clinically detectible illness and their mothers have been included and heavy metal levels in the blood of these subjects have been estimated by Atomic Absorption Spectrophotometer (AAS). Result. Significantly high levels of cadmium and lead have been observed in hypospadias cases; however, all heavy metal levels were present in higher concentration. Conclusion. Higher blood levels of cadmium and lead may be associated with the increased risk of hypospadias.
    03/2014; 2014:714234. DOI:10.1155/2014/714234
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    • "Some associations between dietary factors and the occurrence of hypospadias have been reported in several studies. Frequent consumption of fish was found to be associated with hypospadias; this was allegedly because of an accumulation of environmental chemicals in the fish.6465 A recent study showed that a decreased consumption of fruit, vegetables and protein-rich foods was associated with a higher risk of hypospadias compared to consuming healthy food. "
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    ABSTRACT: During the past few decades, scientific evidence has been accumulated concerning the possible adverse effects of the exposure to environmental chemicals on the well-being of wildlife and human populations. One large and growing group of such compounds of anthropogenic or natural origin is referred to as endocrine-disrupting chemicals (EDCs), due to their deleterious action on the endocrine system. This concern was first focused on the control of reproductive function particularly in males, but has later been expanded to include all possible endocrine functions. The present review describes the underlying physiology behind the cascade of developmental events that occur during sexual differentiation of males and the specific role of androgen in the masculinization process and proper organogenesis of the external male genitalia. The impact of the genetic background, environmental exposures and lifestyle factors in the etiology of hypospadias, cryptorchidism and testicular cancer are reviewed and the possible role of EDCs in the development of these reproductive disorders is discussed critically. Finally, the possible direct and programming effects of exposures in utero to widely use therapeutic compounds, environmental estrogens and other chemicals on the incidence of reproductive abnormalities and poor semen quality in humans are also highlighted.
    Asian Journal of Andrology 01/2014; 16(1):50-9. DOI:10.4103/1008-682X.122199 · 2.60 Impact Factor
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