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- Giwercman, Aleksander, et al.
(author)
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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
- 2007
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In: Pharmacogenetics & Genomics. - : Ovid Technologies (Wolters Kluwer Health). - 1744-6872. ; 17:6, s. 391-401
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Journal article (peer-reviewed)abstract
- 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. DF1 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.
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- Jönsson, Bo A, et al.
(author)
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Inter-population variations in concentrations, determinants of and correlations between 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE): a cross-sectional study of 3161 men and women from Inuit and European populations
- 2005
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In: Environmental Health. - 1476-069X. ; 4:27
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Journal article (peer-reviewed)abstract
- BACKGROUND: The study is part of a collaborative project (Inuendo), aiming to assess the impact of dietary persistent organochlorine pollutants (POPs) on human fertility. The aims with the present study are to analyze inter-population variations in serum concentrations of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE), to assess inter-population variations in biomarker correlations, and to evaluate the relative impact of different determinants for the inter-individual variations in POP-biomarkers. METHOD: In study populations of 3161 adults, comprising Greenlandic Inuits, Swedish fishermen and their wives, and inhabitants from Warsaw, Poland and Kharkiv, Ukraine, serum concentrations of CB-153 and p,p'-DDE, were analysed by gas chromatography-mass spectrometry. RESULTS: The median serum concentrations of CB-153 were for male and female Inuits 200 and 110, for Swedish fishermen 190 and their wives 84, for Kharkiv men and women 44 and 27, and for Warsaw men and women 17 and 11 ng/g lipids, respectively. The median serum concentrations of p,p'-DDE were for Kharkiv men and women 930 and 650, for male and female Inuits 560 and 300, for Warsaw men and women 530 and 380, and for Swedish fishermen 240 and their wives 140 ng/g lipids, respectively. The correlation coefficients between CB-153 and p,p'-DDE varied between 0.19 and 0.92, with the highest correlation among Inuits and the lowest among men from Warsaw. Men had averagely higher serum concentrations of CB-153 and p,p'-DDE, and there were positive associations between age and the POP-biomarkers, whereas the associations with BMI and smoking were inconsistent. Dietary seafood was of importance only in the Inuit and Swedish populations. CONCLUSION: CB-153 concentrations were much higher in Inuits and Swedish fishermen's populations than in the populations from Eastern Europe, whereas the pattern was different for p,p'-DDE showing highest concentrations in the Kharkiv population. The correlations between the POP-biomarkers varied considerably between the populations, underlining that exposure sources differ and that the choice of representative biomarkers of overall POP exposure has to be based on an analysis of the specific exposure situation for each population. Age and gender were consistent determinants of serum POPs; seafood was of importance only in the Inuit and Swedish populations.
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- Stronati, A., et al.
(author)
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Relationships between sperm DNA fragmentation, sperm apoptotic markers and serum levels of CB-153 and p,p '-DDE in European and Inuit populations
- 2006
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In: Reproduction. - : Bioscientifica. - 1470-1626 .- 1741-7899. ; 132:6, s. 949-958
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Journal article (peer-reviewed)abstract
- Persistent organochlorine pollutants (POPs) are suspected to interfere with hormone activity and the normal homeostasis of spermatogenesis. We investigated the relationships between sperm DNA fragmentation, apoptotic markers identified on ejaculated spermatozoa and POP levels in the blood of 652 adult males (200 Inuits from Greenland, 166 Swedish, 134 Polish and 152 Ukrainian). Serum levels of 2, 2', 4, 4', 5, 5'-hexachlorobiphenyl (CB-153), as a proxy of the total POP burden, and of 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE), as a proxy of the total DDT exposure were determined. Sperm DNA fragmentation was measured by using the TUNEL assay, whereas immunofluorescence methods were utilized for detecting proapoptotic (Fas) and anti-apoptotic (Bcl-xL) markers. Both TUNEL assay and apoptotic markers were statistically differed across the four populations. No correlation between neither sperm DNA fragmentation nor apoptotic sperm parameters and the large variations in POPs exposure was observed for the separate study groups. However, considering the European populations taken together, we showed that both %TUNEL positivity and Bcl-xL were related to CB-153 serum levels, whereas our study failed to demonstrate any relations between DDE and %TUNEL positivity and apoptotic sperm biomarkers (Fas and Bcl-xL) in any region or overall regions. These results suggest that CB-153 and related chemicals might alter sperm DNA integrity and Bcl-xL levels in European adult males, but not in the highly exposed Inuit men. Additional issues (genetic background, lifestyle habits and characterization of total xeno-hormonal activities) need to he investigated in order to fully assess the population variations observed.
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- Tiido, Tarmo, et al.
(author)
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Exposure to persistent organochlorine pollutants associates with human sperm Y:X chromosome ratio.
- 2005
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In: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 20:7, s. 1903-1909
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Journal article (peer-reviewed)abstract
- BACKGROUND: During the last decades, there has been concern that exposure to endocrine disruptors, such as persistent organochlorine pollutants (POPs), may contribute to sex ratio changes in offspring of exposed populations. METHODS: To investigate whether exposure to 2,2'4,4'5,5'-hexachlorobiphenyl (CB-153) and dichlorodiphenyl dichloroethene (p,p'-DDE) affect Y:X chromosome proportion, semen of 149 Swedish fishermen, aged 27–67 years, was investigated. The men provided semen and blood for analysis of hormone, CB-153 and p,p'-DDE levels. The proportion of Y- and X-chromosome bearing sperm in semen samples was determined by two-colour fluorescence in situ hybridization (FISH) analysis. RESULTS: Log transformed CB-153 as well as log transformed p,p'-DDE variables were both significantly positively associated with Y chromosome fractions (P-values=0.05 and <0.001, respectively). Neither age, smoking nor hormone levels showed any association with Y-chromosome fractions. CONCLUSIONS: This is the first study to indicate that exposure to POPs may increase the proportion of ejaculated Y-bearing spermatozoa. These data add to the growing body of evidence that exposure to POPs may alter the offspring sex ratio.
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| 10. |
- Tiido, Tarmo, et al.
(author)
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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
- 2007
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In: Molecular Human Reproduction. - : Oxford University Press (OUP). - 1460-2407. ; 13:4, s. 223-229
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Journal article (peer-reviewed)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 < 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.
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