Human exposure to endocrine-disrupting chemicals and prenatal risk factors for cryptorchidism and hypospadias: a nested case-control study.
BACKGROUND
Exposure to xenoestrogens during pregnancy may disturb the development and function of male sexual organs.


OBJECTIVE
In 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.


METHODS
In 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).


RESULTS
TEXB 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.


CONCLUSIONS
We found an increased risk for male urogenital malformations related to the combined effect of environmental estrogens in placenta.
Fernandez
Mariana F
MF
Laboratory of Medical Investigations, San Cecilio University Hospital, Granada, Spain. marieta@ugr.es
Olmos
Begoña
B
Granada
Alicia
A
López-Espinosa
Maria José
MJ
Molina-Molina
José-Manuel
JM
Fernandez
Juan Manuel
JM
Cruz
Milagros
M
Olea-Serrano
Fátima
F
Olea
Nicolás
N
D000328:Adult; D000383:Agriculture; D016022:Case-Control Studies; D003456:Cryptorchidism / Q000453:epidemiology / Q000209:etiology*; D052244:Endocrine Disruptors / Q000633:toxicity*; D004967:Estrogens / Q000633:toxicity*; D005260:Female; D006785:Hospitals, University; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity; D007021:Hypospadias / Q000453:epidemiology / Q000209:etiology*; D007231:Infant, Newborn; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D016273:Occupational Exposure / Q000009:adverse effects*; D018812:Paternal Exposure / Q000009:adverse effects; D010573:Pesticide Residues / Q000633:toxicity*; D010920:Placenta / Q000737:chemistry; D011247:Pregnancy; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D011795:Surveys and Questionnaires
D052244:Endocrine Disruptors; D004967:Estrogens; D006843:Hydrocarbons, Chlorinated; D010573:Pesticide Residues