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1.
  • Qi, Qibin, et al. (författare)
  • FTO genetic variants, dietary intake and body mass index : insights from 177 330 individuals
  • 2014
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:25, s. 6961-6972
  • Tidskriftsartikel (refereegranskat)abstract
    • FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.
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4.
  • Brokken, Leon, et al. (författare)
  • Interactions between polymorphisms in the aryl hydrocarbon receptor signalling pathway and exposure to persistent organochlorine pollutants affect human semen quality.
  • 2014
  • Ingår i: Reproductive Toxicology. - : Elsevier BV. - 1873-1708 .- 0890-6238. ; 49:Jul 30, s. 65-73
  • Tidskriftsartikel (refereegranskat)abstract
    • Persistent organic pollutants (POPs) may affect male reproductive function. Many dioxin-like POPs exert their effects by activation of the aryl hydrocarbon receptor (AHR) signalling pathway. We analysed whether gene-environment interactions between polymorphisms in AHR (R554K) and AHR repressor (AHRR P185A) and serum levels of markers of POP exposure 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene (p,p'-DDE) and 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) are associated with 21 parameters of male reproductive function in 581 proven-fertile European and Greenlandic men. In Greenlandic men, AHR variants significantly modified the association between serum levels of both p,p'-DDE and CB-153 and inhibin B levels, sperm chromatin integrity, and seminal zinc levels. In the total cohort, interactions between AHRR variants and serum levels of CB-153 were associated with sperm chromatin integrity and the expression of the pro-apoptotic marker protein Fas. The data indicate that susceptibility to adverse effects of POP exposure on male reproductive function is dependent on polymorphisms in genes involved in AHR signalling.
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5.
  • Brokken, Leon, et al. (författare)
  • Non-linear association between androgen receptor CAG and GGN repeat lengths and reproductive parameters in fertile European and Inuit men.
  • 2013
  • Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 1872-8057 .- 0303-7207. ; 370:1-2, s. 163-171
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently the dogma that there is an inverse linear association between androgen receptor (AR) CAG and GGN polymorphisms and receptor activity has been challenged. We analysed the pattern of association between 21 male reproductive phenotypes and AR CAG/GGN repeat lengths in 557 proven-fertile men. A linear association was only found between sperm DNA fragmentation index (DFI) and CAG length, and between inhibin B and GGN length. Men with longer CAG then the reference (22-24), had higher oestradiol levels, whereas men with shorter CAG stretches had a higher DFI and a higher proportion of Fas-positive germ cells. Subjects with either short or long CAG had increased seminal levels of prostate-specific antigen and neutral α-glucosidase activity. Compared to men with the median GGN length of 23, those with shorter GGN repeats had higher levels of inhibin B, higher proportions of normal and progressive sperm, and a higher fraction of Fas-positive sperm, while men with longer GGN had higher oestradiol levels. These data indicate that at least for some markers of male reproductive function the association with CAG or GGN repeat length is curvilinear.
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  • Fynbo, J. P. U., et al. (författare)
  • Galaxy counterparts of metal-rich damped Ly alpha absorbers - I. The case of the z=2.35 DLA towards Q2222-0946
  • 2010
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 408:4, s. 2128-2136
  • Tidskriftsartikel (refereegranskat)abstract
    • We have initiated a survey using the newly commissioned X-shooter spectrograph to target candidate relatively metal-rich damped Ly alpha absorbers (DLAs). Our rationale is that high-metallicity DLAs due to the luminosity-metallicity relation likely will have the most luminous galaxy counterparts. In addition, the spectral coverage of X-shooter allows us to search for not only Ly alpha emission, but also rest-frame optical emission lines. We have chosen DLAs where the strongest rest-frame optical lines ([O II], [O III], H beta and H alpha) fall in the near-infrared atmospheric transmission bands. In this first paper resulting from the survey, we report on the discovery of the galaxy counterpart of the z(abs) = 2.354 DLA towards the z = 2.926 quasar Q2222-0946. This DLA is amongst the most metal-rich z > 2 DLAs studied so far at comparable redshifts and there is evidence for substantial depletion of refractory elements on to dust grains. We measure metallicities from Zn II, Si II, Ni II, Mn II and Fe II of -0.46 +/- 0.07, -0.51 +/- 0.06, -0.85 +/- 0.06, -1.23 +/- 0.06 and -0.99 +/- 0.06, respectively. The galaxy is detected in the Ly alpha, [O III] lambda lambda 4959, 5007 and H alpha emission lines at an impact parameter of about 0.8 arcsec (6 kpc at z(abs) = 2.354). Based on the H alpha line, we infer a star formation rate of 10M(circle dot) yr(-1), which is a lower limit due to the possibility of slit loss. Compared to the recently determined H alpha luminosity function for z = 2.2 galaxies, the DLA-galaxy counterpart has a luminosity of L similar to 0.1L*(H alpha). The emission-line ratios are 4.0 (Ly alpha/H alpha) and 1.2 ([O III]/H alpha). In particular, the Ly alpha line shows clear evidence for resonant scattering effects, namely an asymmetric, redshifted (relative to the systemic redshift) component and a much weaker blueshifted component. The fact that the blueshifted component is relatively weak indicates the presence of a galactic wind. The properties of the galaxy counterpart of this DLA are consistent with the prediction that metal-rich DLAs are associated with the most luminous of the DLA-galaxy counterparts.
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8.
  • Fynbo, J. P. U., et al. (författare)
  • Galaxy counterparts of metal-rich damped Ly alpha absorbers - II. A solar-metallicity and dusty DLA at z(abs)=2.58
  • 2011
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 413:4, s. 2481-2488
  • Tidskriftsartikel (refereegranskat)abstract
    • This is the second paper of a series reporting on the results from a survey conducted with the ESO VLT/X-shooter spectrograph. We target high-metallicity damped Lyman alpha absorbers (DLAs) with the aim of investigating the relation between galaxies detected in emission and those detected in absorption. Here, we report on the discovery of the galaxy counterpart of the z(abs) = 2.58 DLA on the line-of-sight to the z = 3.07 quasar SDSS J 091826.16+163609.0 (hereafter Q 0918+1636). The galaxy counterpart of the DLA is detected in the [O iii] lambda 5007 and [O ii] lambda lambda 3726, 3729 emission lines redshifted into the NIR at an impact parameter of 2.0 arcsec (16 kpc at z = 2.58). Ly alpha emission is not detected down to a 3 Sigma detection limit of 5 x 10-18 erg s-1 cm-2, which, compared to the strength of the oxygen lines, implies that Ly alpha emission from this galaxy is suppressed by more than an order of magnitude. The DLA has one of the highest metallicities measured so far at comparable redshifts. We find evidence for substantial depletion of refractory elements on to dust grains. Fitting the main metal line component of the DLA, which is located at z(abs) = 2.5832, we measure the metal abundances from Zn ii, S ii, Si ii, Cr ii, Mn ii, Fe ii and Ni ii to be -0.12 +/- 0.05, -0.26 +/- 0.05, -0.46 +/- 0.05, -0.88 +/- 0.05, -0.92 +/- 0.05, -1.03 +/- 0.05 and -0.78 +/- 0.05, respectively. In addition, we detect absorption in the Lyman and Werner bands of molecular hydrogen (H(2)), which represents the first detection of H(2) molecules with X-shooter. The background quasar Q 0918+1636 is amongst the reddest QSOs at redshifts 3.02 < z < 3.12 from the SDSS catalogue. Its UV to NIR spectrum is well fitted by a composite QSO spectrum reddened by SMC-/LMC-like extinction curves at z(abs) = 2.58 with a significant amount of extinction given by A(V) approximate to 0.2 mag. This supports previous claims that there may be more metal-rich DLAs missing from current samples due to dust reddening of the background QSOs. The fact that there is evidence for dust both in the central emitting regions of the galaxy (as evidenced by the lack of Ly alpha emission) and at an impact parameter of 16 kpc (as probed by the DLA) suggests that dust is widespread in this system.
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  • Fynbo, J. P. U., et al. (författare)
  • Galaxy counterparts of metal-rich damped Lyman-alpha absorbers - II. A solar-metallicity and dusty DLA at z_abs=2.58
  • 2010
  • Annan publikation (populärvet., debatt m.m.)abstract
    • [Abridged]. Here, we report on the discovery of the galaxy counterpart of the z_abs=2.58 DLA on the line-of-sight to the z=3.07 quasar SDSS J091826.16+163609.0. The galaxy counterpart of the DLA is detected in the OIII 5007 and OII 3726,3729 emission lines redshifted into the NIR at an impact parameter of 16 kpc. Ly-alpha emission is not detected. The upper limit implies that Ly-alpha emission from this galaxy is suppressed by more than an order of magnitude. The DLA is amongst the most metal-rich DLAs studied so far at comparable redshifts. We find evidence for substantial depletion of refractory elements onto dust grains. Fitting the main metal line component of the DLA, which is located at z_abs=2.5832 and accounts for at least 85% of the total column density of low-ionisation species, we measure metal abundances from ZnII, SII, SiII, CrII, MnII, FeII and NiII of -0.12, -0.26, -0.46, -0.88, -0.92, -1.03 and -0.78, respectively. In addition, we detect absorption in the Lyman and Werner bands of hydrogen, which represents the first detection of H_2 molecules with X-shooter. The background quasar Q0918+1636 is amongst the reddest QSOs at redshifts 3.02<3.12 from the SDSS catalogue. Its UV to NIR spectrum is well fitted by a composite QSO spectrum reddened by SMC/LMC-like extinction curves at z_abs=2.58 with a significant amount of extinction given by A_V = 0.2 mag. This supports previous claims that there may be more metal-rich DLAs missing from current samples due to dust reddening of the background QSOs. The fact that there is evidence for dust both in the central emitting regions of the galaxy (as evidenced by the lack of Ly-alpha emission) and at an impact parameter of 16 kpc (as probed by the DLA) suggests that dust is widespread in this system.
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  • Hamrin, Kerstin, et al. (författare)
  • Prolonged Exercise-Induced Stimulation of Skeletal Muscle Glucose Uptake Is due to Sustained Increases in Tissue Perfusion and Fractional Glucose Extraction
  • 2011
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 96:4, s. 1085-1092
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: The mechanisms behind the positive effects of physical activity on glucose metabolism in skeletal muscle and the time course of the effects need to be more elucidated. Objective: The aim was to examine the prolonged effects of an acute bout of one-legged exercise on local skeletal muscle glucose utilization and tissue perfusion. Design and Setting: Interstitial glucose concentration, local tissue perfusion, glucose uptake, and effects of insulin infusion were studied 12 h after an acute bout of exercise and without prior exercise. Participants: Ten healthy subjects, five women and five men, participated in the study. Intervention: Microdialysis measurements, (133)Xe clearance, and a 2-h hyperinsulinemic euglycemic clamp were performed on two occasions. Main Outcome Measures: We measured interstitial glucose concentration and tissue perfusion in the quadriceps femoris muscle of both legs. Results: Tissue perfusion (3.3 +/- 0.6 ml x 100 g(-1) x min(-1) vs. 1.4 +/- 0.2 ml x 100 g(-1) x min(-1); P = 0.007) and basal glucose uptake (2.3 +/- 0.5 mu mol x 100 g(-1) x min(-1) vs. 0.9 +/- 0.2 mu mol x 100 g(-1) x min(-1); P = 0.006) were increased in the leg that had exercised compared to the resting leg; the findings in the resting leg were comparable to those in the control experiment without prior exercise. The relative effect of insulin on fractional skeletal muscle glucose uptake was the same in all experimental settings, and insulin did not affect tissue perfusion. Conclusions: The prolonged stimulatory effect of physical exercise on skeletal muscle glucose uptake was mediated via vascular effects combined with an increase in basal glucose transport independent of enhancement of insulin responses.
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12.
  • Høyer, B B, et al. (författare)
  • Body mass index in young school age children in relation to organochlorine compounds in early life: a prospective study.
  • 2014
  • Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 38:7, s. 919-925
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective:To investigate the association between maternal pregnancy and estimated postnatal serum concentrations of the organochlorines 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) and body mass index (BMI) z-scores in five to nine-year-old children.Methods:Maternal sera from the INUENDO birth cohort (2002-2004) comprising mother-child pairs (N=1109) from Greenland, Warsaw (Poland) and Kharkiv (Ukraine) were analysed for CB-153 and p,p'-DDE, using gas chromatography-mass-spectrometry, and were grouped into tertiles for statistical analyses. A toxicokinetic model was used to estimate the first 12 months cumulative exposure to the compounds. Associations between these compounds and child age- and sex-specific BMI z-scores were calculated at follow-up (2010-2012), using multiple linear regression analysis.Results:No clear associations between pregnancy CB-153 and p,p'-DDE and child BMI were observed (the pooled differences in BMI z-score (95% confidence interval) comparing 3rd tertile to 1st tertile were -0.07 (-0.32 to 0.18) and -0.10 (-0.30 to 0.10) kg m(-2), respectively). For postnatal CB-153 and p,p'-DDE and BMI, the overall differences in BMI z-score comparing 3rd tertile to 1st tertile were 0.12 (-0.15 to 0.39) and -0.03 (-0.20 to 0.27) kg m(-2), respectively.Conclusions:This follow-up study of Greenlandic, Polish and Ukrainian populations showed no clear association between pregnancy and postnatal exposure to p,p'-DDE and CB-153 and BMI at the age of five to nine years.International Journal of Obesity accepted article peview online, 10 April 2014; doi:10.1038/ijo.2014.58.
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  • Kvist, Linus, et al. (författare)
  • Serum levels of perfluorinated compounds and sperm Y:X chromosome ratio in two European populations and in Inuit from Greenland.
  • 2012
  • Ingår i: Reproductive Toxicology. - : Elsevier BV. - 1873-1708 .- 0890-6238.
  • Tidskriftsartikel (refereegranskat)abstract
    • This study investigated whether perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS), which exhibit reproductive toxicity in experimental animals, affect sperm sex chromosome ratio. The Y:X ratio was determined by fluorescence in situ hybridization. Serum concentrations of PFOA and PFOS were measured in 607 men from Greenland, Poland and Ukraine using liquid chromatography-tandem mass spectrometry. Data was analyzed by linear and nonlinear regression. We observed no associations between PFOA and Y:X ratio (p=0.845 in a linear model, p=0.296 in a nonlinear model). A positive nonlinear association between PFOS and Y:X ratio was observed (p=0.016), with no association in a linear model (p=0.118). Analyzing the populations separately, a negative trend between categorized PFOS exposure and Y:X ratio was observed for the Inuit (B=-0.002, p=0.044). In conclusion, there was a negative trend between Y:X ratio and PFOS in the Inuit, while there was no association between PFOA and the Y:X ratio in adult men.
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  • Lenters, Virissa, et al. (författare)
  • Serum concentrations of polybrominated diphenyl ethers (PBDEs) and a polybrominated biphenyl (PBB) in men from Greenland, Poland and Ukraine
  • 2013
  • Ingår i: Environment International. - : Elsevier BV. - 1873-6750 .- 0160-4120. ; 61, s. 8-16
  • Tidskriftsartikel (refereegranskat)abstract
    • Many brominated flame retardants (BFRs)-including polybrominated diphenyl ethers (PBDEs)-have been shown to persist in the environment, and some have been associated with adverse health effects. The aim of the present study was to quantify serum concentrations of common brominated flame retardants in Inuit men from across Greenland, and in men from Warsaw, Poland and Kharkiv, Ukraine. Serum was sampled between 2002 and 2004 from men 19 to 50 years of age. 299 samples were analyzed for BDE-28, 47, 99, 100, 153, 154 and 183 and the brominated biphenyl BB-153 using gas chromatography-high resolution mass spectrometry. BDE-47 and BDE-153 were detected in more than 95% of samples from all three populations. All other congeners, except BDE-154, were detected in more than 70% of samples from Greenland; lower detection frequencies were observed in Polish and Ukrainian samples. Concentrations of individual congeners were 2.7 to 15 fold higher in Greenlandic relative to Polish and Ukrainian men. Geometric mean concentrations of the sum of the most abundant PBDEs of the Penta-BDE commercial mixture (BDE-47, 99, 100, 153 and 154) were 6.1, 1.7 and 0.87 ng/g lipids in the Greenlandic, Polish and Ukrainian men, respectively. Furthermore, significant geographical differences in BFR concentrations were observed within Greenland. Principal component analysis revealed distinct clustering of samples by country of origin. The associations between Sigma PBDEs and age were inconsistent, varying from no association in Greenlandic and Polish study populations to a U-shaped relationship in Ukrainians. We report BFR levels for three populations for which sparse biomonitoring data exists. (C) 2013 Elsevier Ltd. All rights reserved.
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  • Leter, Giorgio, et al. (författare)
  • Exposure to Perfluoroalkyl Substances and Sperm DNA Global Methylation in Arctic and European Populations
  • 2014
  • Ingår i: Environmental and Molecular Mutagenesis. - : Wiley. - 1098-2280 .- 0893-6692. ; 55:7, s. 591-600
  • Tidskriftsartikel (refereegranskat)abstract
    • Perfluoroalkyl substances (PFASs) are widely used in a variety of industrial processes and products, and have been detected globally in humans and wildlife. PFASs are suspected to interfere with endocrine signaling and to adversely affect human reproductive health. The aim of the present study was to investigate the associations between exposure to PFASs and sperm global methylation levels in a population of non-occupationally exposed fertile men. Measurements of PFASs in serum from 262 partners of pregnant women from Greenland, Poland and Ukraine, were also carried out by liquid chromatography tandem mass spectrometry. Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) were detected in 97% of the blood samples. Two surrogate markers were used to assess DNA global methylation levels in semen samples from the same men: (a) average DNA methylation level in repetitive DNA sequences (Alu, LINE-1, Sat alpha) quantified by PCR-pyrosequencing after bisulfite conversion; (b) flow cytometric immunodetection of 5-methyl-cytosines. After multivariate linear regression analysis, no major consistent associations between PFASs exposure and sperm DNA global methylation endpoints could be detected. However, since weak but statistically significant associations of different PFASs with DNA hypo- and hypermethylation were found in some of the studied populations, effects of PFASs on sperm epigenetic processes cannot be completely excluded, and this issue warrants further investigation. (C) 2014 Wiley Periodicals, Inc.
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  • Lindh, Christian, et al. (författare)
  • Blood serum concentrations of perfluorinated compounds in men from Greenlandic Inuit and European populations.
  • 2012
  • Ingår i: Chemosphere. - : Elsevier BV. - 1879-1298 .- 0045-6535. ; 88:11, s. 1269-1275
  • Tidskriftsartikel (refereegranskat)abstract
    • Perfluorinated compounds (PFCs), such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), are used in large quantities. They are persistent and found in measurable levels in human serum around the world. They have been associated with developmental, hepatic, and carcinogenic effects in animal studies. The aim of the present study was to describe levels of PFCs in serum among Inuits from Greenland and inhabitants from Warsaw, Poland and Kharkiv, Ukraine. Furthermore, the aim was to define social- and lifestyle related determinants of exposure for these compounds. Serum levels of seven PFCs were analyzed by liquid chromatography/tandem mass spectrometry (LC/MS/MS). The concentrations of PFOS and PFOA were the highest of all PFCs in all three populations with a total amount of almost 90% of the PFCs. The mean levels of PFOS and PFOA were in the Greenlandic Inuits 52 and 4.8ngmL(-1), in Poland 19 and 5.2ngmL(-1), and in Ukraine 8.1 and 1.9ngmL(-1), respectively. Thus, levels of PFCs in the serum of Inuits on Greenland were among the highest described in a general population whereas the levels in Poland were similar to other industrialized countries. The exposure in Ukraine was rather low. In the Greenlandic Inuit population, intake of seafood, tea, age and area of living were significant determinants of PFOS concentrations and explained about 22% of the variation. For the other populations no strong determinants were found.
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18.
  • Lyngso, J., et al. (författare)
  • Menstrual cycle characteristics in fertile women from Greenland, Poland and Ukraine exposed to perfluorinated chemicals: a cross-sectional study
  • 2014
  • Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 29:2, s. 359-367
  • Tidskriftsartikel (refereegranskat)abstract
    • Does perfluorooctane sulfonate (PFOS) and perfluorooctanate (PFOA) exposure disrupt the menstrual cyclicity? The female reproductive system may be sensitive to PFOA exposure, with longer menstrual cycle length at higher exposure. PFOS and PFOA are persistent man-made chemicals. Experimental animal studies suggest they are reproductive toxicants but epidemiological findings are inconsistent. A cross-sectional study including 1623 pregnant women from the INUENDO cohort enrolled during antenatal care visits between June 2002 and May 2004 in Greenland, Poland and Ukraine. Information on menstrual cycle characteristics was obtained by questionnaires together with a blood sample from each pregnant woman. Serum concentrations of PFOS and PFOA were measured by liquid chromatography tandem mass spectrometry. Multiple imputations were performed to account for missing data. The association between PFOS/PFOA and menstrual cycle length (short cycle: 24 days, long cycle: 32 days) and irregularities (7 days in difference between cycles) was analyzed using logistic regression with tertiles of exposure. Estimates are given as adjusted odds ratios (ORs) with 95 confidence intervals (CIs). Higher exposure levels of PFOA were associated with longer menstrual cycles in pooled estimates of all three countries. Compared with women in the lowest exposure tertile, the adjusted OR of long cycles was 1.8 (95 CI: 1.0; 3.3) among women in the highest tertile of PFOA exposure. No significant associations were observed between PFOS exposure and menstrual cycle characteristics. However, we observed a tendency toward more irregular cycles with higher exposure to PFOS [OR 1.7 (95 CI: 0.8; 3.5)]. The overall response rate was 45.3 with considerable variation between countries (91.3 in Greenland, 69.1 in Poland and 26.3 in Ukraine). Possible limitations in our study include varying participation rates across countries; a selected study group overrepresenting the most fertile part of the population; retrospective information on menstrual cycle characteristics; the determination of cut-points for all three outcome variables; and lacking information on some determinants of menstrual cycle characteristics, such as stress, physical activity, chronic diseases and gynecological disorders, thus confounding cannot be excluded. The generalizability of the study results is restricted to fertile women who manage to conceive and women who do not use oral contraceptives when getting pregnant or within 2 months before getting pregnant. To our knowledge only one previous epidemiological study has addressed the possible association between perfluorinated chemical exposure and menstrual disturbances. Though pointing toward different disturbances in cyclicity, both studies suggest that exposure to PFOA may affect the female reproductive function. This study contributes to the limited knowledge on effects of exposure to PFOA and PFOS on female reproductive function and suggests that the female reproductive system may be affected by environmental exposure to PFOA. Supported by a scholarship from Aarhus University Research Foundation. The collection of questionnaire data and blood samples was part of the INUENDO project supported by The European Commission (Contract no. QLK4-CT-2001-00 202), . The Ukrainian part of the study was possible by a grant from INTAS (project 012 2205). Determination of PFOA and PFOS in serum was part of the CLEAR study () supported by the European Commissions 7th Framework Program (FP7-ENV-2008-1-226217). No conflict of interest declared.
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19.
  • Specht, Ina Olmer, et al. (författare)
  • Associations between serum phthalates and biomarkers of reproductive function in 589 adult men.
  • 2014
  • Ingår i: Environment International. - : Elsevier BV. - 1873-6750 .- 0160-4120. ; 66:Feb 26, s. 146-156
  • Tidskriftsartikel (refereegranskat)abstract
    • Phthalates which are widely used, are ubiquitous in the environment and in some human tissues. It is generally accepted that phthalates exert their toxic action by inhibiting Leydig cell synthesis of testosterone, but in vitro studies have also shown anti-androgenic effects at the receptor level. Some cross-sectional studies have shown inverse associations between urinary levels of phthalates and reproductive hormones, but results are conflicting and the evidence base is limited. The aim of this study was to investigate if levels of di-2-ethylhexyl phthalate (DEHP) and diisononyl phthalate (DiNP) metabolites in serum are associated with serum concentrations of male reproductive hormones and semen quality. A secondary aim was to investigate metabolic pathways of DEHP and DiNP on semen quality and reproductive hormones. A cross-sectional sample of 589 spouses of pregnant women from Greenland, Poland and Ukraine were enrolled between 2002 and 2004. The men gave semen and blood samples and were interviewed. Six phthalate metabolites of DEHP and DiNP were measured by liquid chromatography tandem mass spectrometry in serum. The metabolites were summed according to their molar weight. We observed significant inverse associations between serum levels of the metabolites, the proxies and serum testosterone. Negative associations were also discovered between some metabolites and sex hormone-binding globulin, semen volume and total sperm count. Findings are compatible with a weak anti-androgenic action of DEHP metabolites, but less so for DiNP metabolites. Metabolic pathways differed significantly between the three study sites, but without major effect on semen quality or reproductive hormones.
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20.
  • Specht, Ina O., et al. (författare)
  • Relationship between apoptotic markers in semen from fertile men and demographic, hormonal and seminal characteristics
  • 2012
  • Ingår i: Asian Journal of Andrology. - : Medknow. - 1008-682X .- 1745-7262. ; 14:6, s. 890-896
  • Tidskriftsartikel (refereegranskat)abstract
    • Apoptosis in the testis has two putative roles during normal spermatogenesis; limitation of the germ cell population to numbers that can be supported by the Sertoli cells, and, possibly, selective depletion of meiotic and postmeiotic abnormal germ cells. We investigated the demographic and biological correlates of the pro-apoptotic marker Fas and the anti-apoptotic marker Bcl-xL in sperm cells of fertile men. Six hundred and four men from Greenland, Poland and Ukraine were consecutively enrolled during their pregnant wife's antenatal visits. Semen analysis was performed as recommended by the World Health Organization. Immunofluorescence coupled to flow cytometry was utilized for detection of apoptotic markers in the sperm cell. DNA damage was assessed by flow cytometry using both the sperm chromatin structure assay (SCSA) and the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. The percentage of Fas-positive sperm cells was higher in men with high total sperm count (P<0.01), more motile sperms (P=0.04) and fewer sperm head defects (P=0.05). These associations were consistent within and across study regions. Furthermore, testosterone, follicle-stimulating hormone (FSH) and sexual hormone-binding globulin (SHBG) were significantly negatively correlated with Fas within and across regions as well. The data indicated no association between the anti-apoptotic Bcl-xL marker and semen or personal characteristics. The finding of Fas-positive sperm cells associated with better semen quality in a cohort of spouses of pregnant women seems different from previous data obtained in infertile men and warrants further investigation to clarify the biological significance of sperm apoptotic markers. Asian Journal of Andrology (2012) 14, 890-896; doi: 10.1038/aja.2012.76; published online 15 October 2012
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21.
  • Specht, Ina Olmer, et al. (författare)
  • Sperm DNA integrity in relation to exposure to environmental perfluoroalkyl substances - A study of spouses of pregnant women in three geographical regions
  • 2012
  • Ingår i: Reproductive Toxicology. - : Elsevier BV. - 1873-1708 .- 0890-6238. ; 33:4, s. 577-583
  • Tidskriftsartikel (refereegranskat)abstract
    • Perfluoroalkyl substances (PFASs) can interfere with male reproductive function, but evidence in humans is limited. Six hundred four fertile men (199 from Greenland, 197 from Poland and 208 from Ukraine) were enrolled in the study. We measured four PFASs in serum (PFOS, PFOA, PFNA and PFHxS) and concurrent DNA damage in spermatozoa by sperm chromatin structure assay (SCSA) and in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, apoptotic markers in semen (Fas-receptor and Bcl-xL), and reproductive hormones in serum. No association between PFASs and SCSA, apoptotic markers or reproductive hormones emerged. We observed a slight increase in SHBG and TUNEL-positivity with increased PFOA exposure in men from Greenland. Thus, consistent evidence that PFAS exposure interferes with sperm DNA fragmentation, apoptosis or reproductive hormones was not found. (C) 2012 Elsevier Inc. All rights reserved.
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22.
  • Toft, G., et al. (författare)
  • Exposure to perfluorinated compounds and human semen quality in arctic and European populations
  • 2012
  • Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 27:8, s. 2532-2540
  • Tidskriftsartikel (refereegranskat)abstract
    • Perfluorinated compounds (PFCs) have been suspected to adversely affect human reproductive health. The aim of this study was to investigate the associations between PFC exposure and male semen quality. PFCs were measured in serum from 588 partners of pregnant women from Greenland, Poland and Ukraine who provided a semen sample, using liquid chromatography tandem mass spectrometry. Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) could be detected in 97 of the samples. The associations between levels of these compounds and semen volume, sperm concentration, total sperm count, motility and morphology were assessed. Across countries, sperm concentration, total sperm count and semen volume were not consistently associated with PFOS, PFOA, PFHxS or PFNA levels. The proportion of morphologically normal cells was 35 lower [95 confidence interval (CI): 466) for the third tertile of PFOS exposure as compared with the first. A similar reduction was found in relation to increasing PFHxS levels. At the third PFOA exposure tertile, the percentage of motile spermatozoa was 19 (95 CI: 1 to 39) higher than in the first. The most robust finding in the present study was the negative associations between PFOS exposure and sperm morphology suggesting adverse effects of PFOS on semen quality, possibly due to interference with the endocrine activity or sperm membrane function. It cannot be excluded that this association and the positive association between PFOA and semen motility, which was not consistent across countries, might represent a chance finding due to the multiple statistical tests being performed.
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23.
  • Toft, Gunnar, et al. (författare)
  • Exposure to Polybrominated Diphenyl Ethers and Male Reproductive Function in Greenland, Poland and Ukraine.
  • 2014
  • Ingår i: Reproductive Toxicology. - : Elsevier BV. - 1873-1708 .- 0890-6238. ; 43, s. 1-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Animal and a few human studies suggest that polybrominated diphenyl ethers (PBDEs) may affect male reproductive function. The aim of the present study was to evaluate if male reproductive function was associated with serum level of PBDEs. We evaluated, in a cross-sectional study, the effects of environmental exposure to BDE-47 and BDE-153 on reproductive hormones and semen quality, including markers of DNA damage and apoptosis, in 299 spouses of pregnant women from Greenland, Poland and Ukraine. Adjusted linear regression models indicated no strong associations between BDE-47 or BDE-153 exposure and markers of male semen quality or reproductive hormones. In the largest study to date we demonstrate that BDE-47 and BDE-153 exposure was not associated with altered semen characteristics or reproductive hormones, indicating that male reproductive function is not affected by the exposure level of these compounds in fertile European or Arctic populations.
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24.
  • Toft, Gunnar, et al. (författare)
  • Fetal loss and maternal serum levels of 2,2 ',4,4 ',5,5 '-hexachlorbiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p '-DDE) exposure: a cohort study in Greenland and two European populations
  • 2010
  • Ingår i: Environmental Health. - 1476-069X. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In the present study, the aim is to examine the risk of fetal loss related to environmental 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) or 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) exposure. Methods: We related LC/MS/MS measurements of CB-153 and p, p'-DDE in serum samples to interview-data on previous fetal loss in populations of pregnant women from Poland, Ukraine and Greenland. Results: In total, 1710 women were interviewed, and 678 of these had at least one previous pregnancy. The risk of ever experiencing a fetal loss increased at higher levels of CB-153 and p, p'-DDE exposure, with an adjusted odds ratio (OR) of 2.4; confidence interval (CI) (1.1-5.5) for CB-153>200 ng/g lipid compared to 0-25 ng CB-153/g lipid and OR of 2.5 CI (0.9-6.6) for p, p'-DDE>1500 ng/g lipid compared to 0-250 ng DDE/g lipid. However, no clear dose response associations were observed. The results further suggest that high level of organochlorine serum concentrations may be related to repeated loss. Conclusions: The risk of fetal loss may increase at higher levels of CB-153 and p, p'-DDE exposure, although lack of dose response and inconsistencies between countries did not allow for firm conclusions.
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25.
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