Androgen receptor gene CAG repeat length as a modifier of the association between persistent organohalogen pollutant exposure markers and semen characteristics.
OBJECTIVE
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<or=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.
Giwercman
Aleksander
A
Molecular Reproductive Medicine Research Unit, Department of Clinical Sciences, Reproductive Medicine Centre, Malmö University Hospital, Lund University, Malmö, Sweden. aleksander.giwercman@med.lu.se
Rylander
Lars
L
Rignell-Hydbom
Anna
A
Jönsson
Bo A G
BA
Pedersen
Henning S
HS
Ludwicki
Jan K
JK
Lesovoy
Vladimir
V
Zvyezday
Valentyna
V
Spano
Marcello
M
Manicardi
Gian-Carlo
GC
Bizzaro
Davide
D
Bonefeld-Jørgensen
Eva C
EC
Toft
Gunnar
G
Bonde
Jens Peter
JP
Giwercman
Charlotte
C
Tiido
Tarmo
T
Giwercman
Yvonne Lundberg
YL
D000328:Adult; D053938:DNA Fragmentation / Q000187:drug effects; D003633:Dichlorodiphenyl Dichloroethylene / Q000097:blood / Q000633:toxicity; D052244:Endocrine Disruptors / Q000097:blood / Q000633:toxicity; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000097:blood / Q000633:toxicity*; D006801:Humans; D006846:Hydrocarbons, Halogenated / Q000633:toxicity*; D008297:Male; D018598:Minisatellite Repeats; D010597:Pharmacogenetics; D011078:Polychlorinated Biphenyls / Q000097:blood / Q000633:toxicity; D011110:Polymorphism, Genetic; D011944:Receptors, Androgen / Q000235:genetics*; D012661:Semen / Q000187:drug effects* / Q000378:metabolism*; D013076:Sperm Count; D018911:Trinucleotide Repeats
C410798:AR protein, human; D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D006846:Hydrocarbons, Halogenated; D011944:Receptors, Androgen; D003633:Dichlorodiphenyl Dichloroethylene; D011078:Polychlorinated Biphenyls; C014024:2,4,5,2',4',5'-hexachlorobiphenyl