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Androgen receptor gene CAG repeat length as a modifier of the association between persistent organohalogen pollutant exposure markers and semen characteristics

Giwercman, Aleksandera; Rylander, Larsb; Rignell-Hydbom, Annab; Jönsson, Bo A.G.b; Pedersen, Henning S.c; Ludwicki, Jan K.f; Lesovoy, Vladimirg; Zvyezday, Valentynah; Spano, Marcelloi; Manicardi, Gian-Carloj; Bizzaro, Davidek; Bonefeld-Jørgensen, Eva C.d; Toft, Gunnare; Bonde, Jens Petere; Giwercman, Charlottea; Tiido, Tarmoa; Giwercman, Yvonne LundbergaINUENDO

Pharmacogenetics and Genomics: June 2007 - Volume 17 - Issue 6 - p 391-401
doi: 10.1097/01.fpc.0000236329.26551.78
ORIGINAL ARTICLES
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Objectives Exposure to persistent organohalogen pollutants was suggested to impair male reproductive function. A gene–environment interaction has been proposed. No genes modifying the effect of persistent organohalogen pollutants on reproductive organs have yet been identified. We aimed to investigate whether the CAG and GGN polymorphisms in the androgen receptor gene modify the effect of persistent organohalogen pollutant exposure on human sperm characteristics.

Methods Semen and blood from 680 men [mean (SD) age 34 (10) years] from Greenland, Sweden, Warsaw (Poland) and Kharkiv (Ukraine) were collected. Persistent organohalogen pollutant exposure was assessed by measuring serum levels of 2,2′,4,4′,5,5′-hexachlorobiphenyl (CB-153) and dichlorodiphenyl dichloroethene (p,p′-DDE). Semen characteristics (volume, sperm concentration, total count, proportion of progressively motile and morphology) and DNA fragmentation index (DFI) were determined. CAG and GGN repeat lengths were determined by direct sequencing of leukocyte DNA.

Results A statistically significant interaction was found between the CB-153 group and CAG repeat category in relation to sperm concentration and total sperm count (P=0.03 and 0.01, respectively). For p,p′-DDE, in the European cohorts a significant interaction was found in relation to DFI (P=0.01). For CAG<20, sperm concentration and total sperm count were 35 and 42% lower, respectively, when the group with CB-153 exposure above median was compared with that below the median. DFI was 40% higher in the high p,p′-DDE exposure group for CAG≤21.

Conclusions This study indicated that the androgen receptor CAG repeat length might modify the susceptibility of an individual to the adverse effects of persistent organohalogen pollutant exposure on semen quality. Other studies regarding this matter are warranted.

aMolecular Reproductive Medicine Research Unit, Department of Clinical Sciences, Reproductive Medicine Centre, Malmö University Hospital, Lund University, Malmö, Sweden

bDivision of Occupational and Environmental Medicine and Psychiatric Epidemiology, Lund University, Lund University Hospital, Lund, Sweden

cCentre for Arctic Environmental Medicine, Nuuk, Greenland

dInstitute of Public Health, Department of Occupational and Environmental Medicine, University of Aarhus, Aarhus, Denmark

eDepartment of Occupational Medicine, Aarhus University Hospital, Aarhus, Denmark

fDepartment of Environmental Toxicology, National Institute of Hygiene, Warsaw, Poland

gRegional Clinical Center of Urology and Nephrology, Italy

hLaboratory of Human Reproduction, Kharkiv State Medical University, Kharkiv, Ukraine

iSection of Toxicology and Biomedical Sciences, BIOTEC-MED, ENEA Casaccia Research Centre, Rome

jUniversity of Modena and Reggio Emilia, Reggio Emilia, Italy

kIstituto di Biologia e Genetica Università Politecnica delle Marche, Ancona, Italy

lwww.inuendo.dk

Correspondence and requests for reprints to Professor Aleksander Giwercman, Fertility Centre, Malmö University Hospital, SE 205 02 Malmö, Sweden

Tel: +46 40 39 11 29; fax: +46 40 33 82 66; e-mail: aleksander.giwercman@med.lu.se

The INUENDO Project: Biopersistent organochlorines in diet and human fertility. Epidemiological studies of time to pregnancy and semen quality in Inuit and European populations, is supported by The European Commission to the 5th Framework Programme Quality of Life and Management of living resources, Key action four on environment and health, (Contract no. QLK4-CT-2001–00202), running 01.01.02–30.06.05. www.inuendo.dk. The Ukrainian part of the study was supported by a grant from INTAS (Contract no. 2001 2205). The Swedish part of the study has also been funded by the Swedish Medical Research Council (Grant No: 521-2004-6072) and the Swedish Research Council for Environment, Agricultural sciences and Spatial Planning.

Received 28 April 2006 Accepted 18 July 2006

© 2007 Lippincott Williams & Wilkins, Inc.