Negative effects of serum p,p′-DDE on sperm parameters and modification by genetic polymorphisms

Objective: Effects of ambient exposure to DDT and its metabolites (DDE-DDT) on human sperm parameters and the role of genetic polymorphisms in modifying the association were investigated. Methods: Demographics, medical history data, blood and semen samples were obtained from the first 336 male partners of couples presenting to 2 infertility clinics. Serum was analyzed for organochlorines (OC) and DNA for polymorphisms in GSTM1, GSTT1, GSTP1 and CYP1A1. Men with each sperm parameter considered low by WHO criteria (concentration < 20 million/mL, motility < 50%, morphology < 4%) were compared to men with all normal sperm parameters in logistic regression models, controlling for sum of other OC pesticides. Results: High DDE-DDT level was associated with significantly increased odds for all 3 low sperm parameters. The risk of low motility with high DDE-DDT exposure was increased in men with the GSTT1 null genotype compared to those with GSTT1 intact (odds ratio (OR) = 4.19, 95% confidence interval (CI) 1.05-16.78 and OR = 3.57,1.43-8.93, respectively). Risk for low morphology in men with high DDE-DDT and one or both CYP1A1*2A alleles was lower compared to men with the common CYP1A1 alleles (OR = 2.18, 0.78-6.07 vs. OR = 3.45,1.32-9.03, respectively). Similar results were obtained for men with low DDE-DDT exposure. Effects of high DDE-DDT on low sperm concentration (OR = 2.53, 1.0-6.31) was unaffected by the presence of the polymorphisms. Conclusion: High DDE-DDT exposure adversely affected all 3 sperm parameters and its effects were exacerbated by the GSTT1 null polymorphism and by the CYP1A1 common alleles. (C) 2009 Elsevier Inc. All rights reserved.