Human Exposure to Endocrine-Disrupting Chemicals and Prenatal Risk Factors for Cryptorchidism and Hypospadias: A Nested Case–Control Study

Abstract

BackgroundExposure to xenoestrogens during pregnancy may disturb the development and function of male sexual organs.ObjectiveIn this study we aimed to determine whether the combined effect of environmental estrogens measured as total effective xenoestrogen burden (TEXB) is a risk factor for male urogenital malformations.MethodsIn a case–control study, nested in a mother–child cohort (n = 702) established at Granada University Hospital, we compared 50 newborns with diagnosis of cryptorchidism and/or hypospadias with 114 boys without malformations matched by gestational age, date of birth, and parity. Controls did not differ from the total cohort in confounding variables. TEXB and levels of 16 organochlorine pesticides were measured in placenta tissues. Characteristics of parents, pregnancy, and birth were gathered by questionnaire. We used conditional and unconditional regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsTEXB from organohalogenated compounds was detectable in 72% and 54% of case and control placentas, respectively. Compared with controls, cases had an OR for detectable versus non-detectable TEXB of 2.82 (95% CI, 1.10–7.24). More pesticides were detected in cases than in controls (9.34 ± 3.19 vs. 6.97 ± 3.93). ORs for cases with detectable levels of pesticides, after adjusting for potential confounders in the conditional regression analysis, were o,p′-DDT (OR = 2.25; 95% CI, 1.03–4.89), p,p′-DDT (OR = 2.63; 95% CI, 1.21–5.72), lindane (OR = 3.38; 95% CI, 1.36–8.38), mirex (OR = 2.85; 95% CI, 1.22–6.66), and endosulfan alpha (OR = 2.19; 95% CI, 0.99–4.82). Engagement of mothers in agriculture (OR = 3.47; 95% CI, 1.33–9.03), fathers’ occupational exposure to xenoestrogens (OR = 2.98; 95% CI, 1.11–8.01), and history of previous stillbirths (OR = 4.20; 95% CI, 1.11–16.66) were also associated with risk of malformations.ConclusionsWe found an increased risk for male urogenital malformations related to the combined effect of environmental estrogens in placenta.

Prenatal exposure to DDT in malaria endemic region following indoor residual spraying and in non-malaria coastal regions of South Africa

“…Therefore, of major concern is the possible impact of exposure to DDT on reproductive health including birth outcomes (Eskenazi et al, 2009;Fernandez et al, 2007).…”

Association of variants in genes involved in environmental chemical metabolism and risk of cryptorchidism and hypospadias

“…1,2 However, epidemiological studies on this issue have produced conflicting results. [3][4][5] The effect of EEDs would depend on several factors, including the dosage of EED exposure, the developmental stage in which EED exposure occurred and inter-individual variability in genetic susceptibility to the effects of EED exposure.…”

Risk of cryptorchidism and hypospadias among boys of maternal hairdressers – a Danish population-based cohort study

“…This hypothesis has been supported by a number of previous observations. In a Spanish case-control study, placental levels of xenoestrogenic activity were increased among children with cryptorchidism or hypospadias compared to children without these genital tract malformations (29). Assessments of possible adverse health effects of chemicals have generally been restricted to single chemical compounds and not mixtures.…”