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Negative effects of serum p,p-DDE on sperm parameters and modification by genetic polymorphisms
Authors:Bridget M. Messaros  Guanghui Liu  Karen Friderici  Douglas Daly  Nigel Paneth
Affiliation:a Department of Epidemiology, Michigan State University, A632 West Fee Hall, East Lansing, MI 48823, USA
b Department of Animal and Food Sciences, University of Kentucky, Lexington, KY, USA
c Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA
d Department of Microbiology and Human Genetics, Michigan State University, East Lansing, MI, USA
e Grand Rapids Infertility and IVF, Grand Rapids, MI, USA
f Department of Obstetrics and Gynecology, Michigan State University, East Lansing, MI, USA
Abstract:

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.
Keywords:8-OHdG, 8-hydroxy-2&prime  -deoxyguanosine   DDE-DDT, sum of DDE and DDT   p,p&prime  -DDT, dichlorodiphenyltrichloroethane   CYP, cytochrome P-450   GST, glutathione S-transferase   HCB, hexachlorobenzene   LOD, level of detection   OC, organochlorine   OCP, other chlorinated pesticides   PAH, polycyclic aromatic hydrocarbon   sumPCB, sum of polychlorinated biphenyls   PCR, polymerase chain reaction   p,p&prime  -DDE, p,p&prime  -Dichlorodiphenyl-dichloroethylene   ppb, parts per billion   WHO, World Health Organization
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