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Modifying effect of the AR gene trinucleotide repeats and SNPs in the AHR and AHRR genes on the association between persistent organohalogen pollutant exposure and human sperm Y : X ratio

Tiido, Tarmo LU ; Rignell-Hydbom, Anna LU ; Jönsson, Bo A LU ; Rylander, Lars LU ; Giwercman, Aleksander LU and Giwercman, Yvonne LU (2007) In Molecular Human Reproduction 13(4). p.223-229
Abstract
Persistent organohalogen pollutants (POPs) have been suggested to be involved in changing the proportion of ejaculated Y-bearing sperm. The androgen receptor (AR), aryl hydrocarbon receptor (AHR) and aryl hydrocarbon receptor repressor (AHRR) may modulate the effect of POPs with regard to previously observed sperm Y : X ratio changes. The objective of this study was to investigate whether sperm Y : X ratio changes in subjects exposed to 2,2'4,4'5,5'-hexachlorobiphenyl (CB-153) and dichlorodiphenyl dichloroethene (p,p'-DDE) were modified by polymorphisms in the AR, AHR and AHRR genes. Semen for analysis of Y- and X-bearing sperm by two-colour fluorescence in situ hybridization and blood for leukocyte DNA genotyping and analysis of CB-153... (More)
Persistent organohalogen pollutants (POPs) have been suggested to be involved in changing the proportion of ejaculated Y-bearing sperm. The androgen receptor (AR), aryl hydrocarbon receptor (AHR) and aryl hydrocarbon receptor repressor (AHRR) may modulate the effect of POPs with regard to previously observed sperm Y : X ratio changes. The objective of this study was to investigate whether sperm Y : X ratio changes in subjects exposed to 2,2'4,4'5,5'-hexachlorobiphenyl (CB-153) and dichlorodiphenyl dichloroethene (p,p'-DDE) were modified by polymorphisms in the AR, AHR and AHRR genes. Semen for analysis of Y- and X-bearing sperm by two-colour fluorescence in situ hybridization and blood for leukocyte DNA genotyping and analysis of CB-153 and p,p'-DDE concentrations were obtained from 195 Swedish fishermen. The polymorphic CAG and GGN repeats in the AR and the R554K and P185A single-nucleotide polymorphisms in the AHR and AHRR genes, respectively, were determined by direct sequencing and allele-specific PCR. The effect of p,p'-DDE was modified by CAG or GGN repeat category in relation to the proportion of Y-bearing sperm (P = 0.005 and 0.02 for CAG and GGN, respectively). Moreover, p,p'-DDE, but not CB-153, levels were associated with Y-sperm proportion in men with CAG < 22 (P < 0.001), but not in those carrying CAG >= 22 (P = 0.73). This association was even more pronounced in subjects carrying a short CAG repeat in combination with an AHRR G-allele. The association in regard to p,p'-DDE was found for GGN = 23 but not for the GGN < 23 or GGN > 23 subgroups (P = 0.01, 0.44 and 0.99, respectively). In conclusion The endocrine-disrupting action of POPs, in relation to the observed changes in sperm Y : X ratio, may be modulated by the genes involved in sex steroid and dioxin-mediated pathways. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
POPs, sperm Y : X ratio, aryl hydrocarbon receptor, polymorphisms, androgen receptor
in
Molecular Human Reproduction
volume
13
issue
4
pages
223 - 229
publisher
Oxford University Press
external identifiers
  • wos:000245511500003
  • scopus:34147108090
ISSN
1460-2407
DOI
10.1093/molehr/gal114
language
English
LU publication?
yes
id
9e8baeb3-01f1-4216-b258-c0969fb94222 (old id 667443)
date added to LUP
2008-01-03 10:37:04
date last changed
2017-09-10 03:37:06
@article{9e8baeb3-01f1-4216-b258-c0969fb94222,
  abstract     = {Persistent organohalogen pollutants (POPs) have been suggested to be involved in changing the proportion of ejaculated Y-bearing sperm. The androgen receptor (AR), aryl hydrocarbon receptor (AHR) and aryl hydrocarbon receptor repressor (AHRR) may modulate the effect of POPs with regard to previously observed sperm Y : X ratio changes. The objective of this study was to investigate whether sperm Y : X ratio changes in subjects exposed to 2,2'4,4'5,5'-hexachlorobiphenyl (CB-153) and dichlorodiphenyl dichloroethene (p,p'-DDE) were modified by polymorphisms in the AR, AHR and AHRR genes. Semen for analysis of Y- and X-bearing sperm by two-colour fluorescence in situ hybridization and blood for leukocyte DNA genotyping and analysis of CB-153 and p,p'-DDE concentrations were obtained from 195 Swedish fishermen. The polymorphic CAG and GGN repeats in the AR and the R554K and P185A single-nucleotide polymorphisms in the AHR and AHRR genes, respectively, were determined by direct sequencing and allele-specific PCR. The effect of p,p'-DDE was modified by CAG or GGN repeat category in relation to the proportion of Y-bearing sperm (P = 0.005 and 0.02 for CAG and GGN, respectively). Moreover, p,p'-DDE, but not CB-153, levels were associated with Y-sperm proportion in men with CAG &lt; 22 (P &lt; 0.001), but not in those carrying CAG &gt;= 22 (P = 0.73). This association was even more pronounced in subjects carrying a short CAG repeat in combination with an AHRR G-allele. The association in regard to p,p'-DDE was found for GGN = 23 but not for the GGN &lt; 23 or GGN &gt; 23 subgroups (P = 0.01, 0.44 and 0.99, respectively). In conclusion The endocrine-disrupting action of POPs, in relation to the observed changes in sperm Y : X ratio, may be modulated by the genes involved in sex steroid and dioxin-mediated pathways.},
  author       = {Tiido, Tarmo and Rignell-Hydbom, Anna and Jönsson, Bo A and Rylander, Lars and Giwercman, Aleksander and Giwercman, Yvonne},
  issn         = {1460-2407},
  keyword      = {POPs,sperm Y : X ratio,aryl hydrocarbon receptor,polymorphisms,androgen receptor},
  language     = {eng},
  number       = {4},
  pages        = {223--229},
  publisher    = {Oxford University Press},
  series       = {Molecular Human Reproduction},
  title        = {Modifying effect of the AR gene trinucleotide repeats and SNPs in the AHR and AHRR genes on the association between persistent organohalogen pollutant exposure and human sperm Y : X ratio},
  url          = {http://dx.doi.org/10.1093/molehr/gal114},
  volume       = {13},
  year         = {2007},
}