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Sökning: WFRF:(Spanò Marcello)

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2.
  • Bonefeld-Jorgensen, Eva C, et al. (författare)
  • Xenoestrogenic activity in blood of European and Inuit populations
  • 2006
  • Ingår i: Environmental Health. - 1476-069X. ; 5:12
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Human exposure to persistent organic pollutants (POPs) is ubiquitous and found in all individuals. Studies have documented endocrine disrupting effects and impact on reproduction. The aim of the present study was to compare the level of xenoestrogenic activity in serum of groups with varying POP exposure, and to evaluate correlations to the POP biomarkers, 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE). METHODS: The study included 358 men: Greenlandic Inuit's, Swedish fishermen, and Warsaw (Poland) and Kharkiv (Ukraine) inhabitants. Xenoestrogenicity of serum extracts alone (XER) and XER competitive (XERcomp) effect on 17beta-estradiol induced estrogen receptor (ER) transactivity were assessed in the hormone free, lipophilic serum fraction containing the POPs using the MVLN human breast cancer cell line. RESULTS: No agonistic XER activity was exhibited for Inuit serum samples, while 12 - 24% of the European samples had detectable agonistic XER activity. On the contrary, 71% of Inuit serum samples antagonized XERcomp compared to 7 - 30 % in the other regions. XER and XERcomp were not or weakly correlated to the two POP markers. XER activity of Inuit samples was negatively associated to levels of CB-153 and p,p'-DDE. For the Warsaw group a positive and negative correlation between XER and p,p'-DDE and estradiol equivalence level and CB-153 levels was found. CONCLUSION: No strong consistent association between xenoestrogenic net activity and the two POP markers was found. The results showed that the selected POP markers alone can not predict the integrated xenoestrogenic serum activity. Correlations to the POP markers were found at the extreme edge; the Inuit's and Warsaw study groups eliciting high frequency of samples with ER antagonistic and agonistic activity, respectively. We suggest that the variation in xenoestrogenic serum activity reflects differences in POP exposure mixture, genetic factors and/or life style factors.
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3.
  • Bungum, Mona, et al. (författare)
  • Sperm chromatin structure assay parameters measured after density gradient centrifugation are not predictive for the outcome of ART
  • 2008
  • Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 23:1, s. 41374-41374
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND The sperm chromatin structure assay (SCSA) parameter DNA fragmentation index (DFI) has been shown to predict in vivo and in vitro fertility. So far most SCSA studies have been based on SCSA analysis performed on neat semen. The aim of this study is to assess whether SCSA analysis of sperm prepared by density gradient centrifugation (DGC) could add more information in regard to the prediction of treatment outcome. METHODS The study included 510 assisted reproductive technique (ART) cycles. SCSA was performed in neat semen and post DGC. SCSA results were expressed in terms of DFI and high DNA stainability (HDS) cell fractions. The outcome parameter was clinical pregnancy (CP). RESULTS Scatter-plot diagrams demonstrated that for DGC samples, no DFI cut-off values could be set for in vivo or in vitro fertility. In intrauterine insemination, IVF and ICSI groups the mean difference (95% CI) in DFI post DGC between those who achieved CP and those who did not was 0.2% (-1.7 to 2.0%), 0.4% (-1.9 to 2.8%) and 1.3% (-3.1 to 5.9%), respectively, none of these being statistically significant. The corresponding differences for HDS were 0.1% (-1.3 to 1.5%), 0.1% (-0.7 to 0.9%) and 0.6% (-1.6 to 2.7%), respectively (all P-values >0.6). CONCLUSIONS SCSA performed in semen prepared by DGC cannot predict the outcome of ART.
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  • Consales, Claudia, et al. (författare)
  • Exposure to persistent organic pollutants and sperm DNA methylation changes in Arctic and European populations.
  • 2016
  • Ingår i: Environmental and Molecular Mutagenesis. - : Wiley. - 1098-2280 .- 0893-6692. ; 57:3, s. 200-209
  • Tidskriftsartikel (refereegranskat)abstract
    • Persistent organic pollutants (POPs), such as PCBs (polychlorinated biphenyls) and DDT [1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane], are environmental contaminants with potential endocrine disrupting activity. DNA methylation levels in peripheral blood lymphocytes have been associated with serum concentrations of POPs in Greenland Inuit and Korean populations. Greenland Inuits are characterized by the highest worldwide POP levels. In this cross-sectional study we evaluated the relationship between serum POP concentrations and DNA methylation levels in sperm of non-occupationally exposed fertile men from Greenland, Warsaw (Poland), and Kharkiv (Ukraine). Serum levels of PCB-153 [1,2,4-trichloro-5-(2,4,5-trichlorophenyl)benzene], as a proxy of the total PCBs body burden, and of p,p'-DDE [1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene], the main metabolite of DDT were measured. Sperm DNA methylation level was assessed globally by flow cytometric (FCM) immunodetection of 5-methyl-cytosines and at specific repetitive DNA sequences (Alu, LINE-1, Satα) by PCR-pyrosequencing after bisulfite conversion. Multivariate linear regression analysis was applied to investigate correlations between serum POP concentrations and DNA methylation. No consistent associations between exposure to POPs and sperm DNA methylation at repetitive DNA sequences were detected. A statistically significant global decrease in methylation was associated with exposure to either POP by FCM analysis. This is the first study to investigate environmental exposure to POPs and DNA methylation levels considering sperm as the target cells. Although POP exposure appears to have a limited negative impact on sperm DNA methylation levels in adult males, the global hypomethylation detected by one of the methods applied suggests that further investigation is warranted. Environ. Mol. Mutagen., 2015. © 2015 Wiley Periodicals, Inc.
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  • Giwercman, Aleksander, et al. (författare)
  • Androgen receptor gene CAG repeat length as a modifier of the association between persistent organohalogen pollutant exposure markers and semen characteristics
  • 2007
  • Ingår i: Pharmacogenetics & Genomics. - : Ovid Technologies (Wolters Kluwer Health). - 1744-6872. ; 17:6, s. 391-401
  • Tidskriftsartikel (refereegranskat)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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10.
  • Giwercman, Aleksander, et al. (författare)
  • Sperm chromatin structure assay as an independent predictor of fertility in vivo: a case-control study.
  • 2010
  • Ingår i: International Journal of Andrology. - : Wiley. - 1365-2605 .- 0105-6263. ; 33, s. 221-227
  • Tidskriftsartikel (refereegranskat)abstract
    • Summary Standard sperm parameters have a limited power for prediction of the chance of natural conception. Recent studies have indicated that the sperm chromatin structure assay (SCSA) DNA fragmentation index (DFI), a measure for the fraction of sperms with DNA damage, is associated with fertility in vivo. The aim of this study was to evaluate the value of this parameter for prediction of infertility. One hundred and twenty-seven men from infertile couples with no known female factor and 137 men with proven fertility were included. Semen analysis was performed as recommended by the WHO. DFI was assessed using SCSA. Logistic binary regression was used to compute the odds ratios (OR) for infertility. As compared with men with a DFI <10%, men with a DFI between 10% and 20% had an increased risk for infertility (OR 2.5, 95% CI: 1.0-6.1). This was also true for men with a DFI >20% (OR 8.4; 95% CI: 3.0-23). In men with normal standard semen parameters (sperm concentration, motility and morphology) the OR for infertility was increased with DFI >20% (OR 5.1, 95% CI: 1.2-23), whereas if one of the standard semen parameters was abnormal, the OR for infertility was increased already at DFI above 10% (OR 16, 95% CI: 4.2-60). We conclude that SCSA DFI adds to the value of semen analysis in prediction of the chance of natural conception.
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  • Jönsson, Bo A, et al. (författare)
  • 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
  • Ingår i: Environmental Health. - 1476-069X. ; 4:27
  • Tidskriftsartikel (refereegranskat)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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  • 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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14.
  • Long, Manhai, et al. (författare)
  • Dioxin-like activities in serum across European and Inuit populations
  • 2006
  • Ingår i: Environmental Health. - 1476-069X. ; 5:14
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Persistent organic pollutants (POPs) such as polychlorinated dibenzo-p-dioxins/furans, polychlorinated biphenyls (PCBs) and organochlorine pesticides can cause a series of adverse effects on e.g. reproduction in animals and humans, many of which involve the aryl hydrocarbon receptor (AhR). The aim of the present study was to compare the integrated serum level of AhR mediated activity among European and Inuit populations, and evaluate whether the activity was associated to the selected POP markers, 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE). METHODS: The study included 338 males from Greenland (Inuit's), Sweden, Warsaw (Poland) and Kharkiv (Ukraine). The AhR transactivity of serum extracts alone (AhRag) and competitive AhR activity (AhRcomp) upon co-exposure with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were determined in the lipophilic serum fraction containing the POPs using the AhR mediated luciferase reporter Hepa1.12cR cell assay. RESULTS: The European groups showed higher median level of AhR-TEQ (TCDD toxic equivalents) compared to the Inuit's, whereas higher incidence of Inuits sample further induced AhRcomp activity. Neither AhRag nor AhR-TEQ were correlated to CB-153 or p,p'-DDE for any of the study groups. Multiple regressions showed a significant heterogeneity of association between the CB-153 and the AhRcomp across the study groups, and accordingly a negative association between AhRcomp and CB-153 was found for the Kharkiv group. CONCLUSION: No consistent correlation between AhR activities and two POP markers was found. Although the difference of AhRag between European and Inuit men could not be explained by CB-153 or p,p'-DDE levels alone, we believe that the variation of AhR serum activity reflects different pattern of POP exposure, genetics and/or life style factors.
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  • Long, Manhai, et al. (författare)
  • Relation between serum xenobiotic-induced receptor activities and sperm DNA damage and sperm apoptotic markers in European and Inuit populations
  • 2007
  • Ingår i: Reproduction. - 1470-1626. ; 133:2, s. 517-530
  • Tidskriftsartikel (refereegranskat)abstract
    • Persistent organic pollutants (POPs) can interfere with hormone activities and are suspected as endocrine disrupters involved in disorders, e.g. reproductive disorders. We investigated the possible relation between the actual integrated serum xenoestrogenic, xenoandrogenic and aryl hydrocarbon receptor (AhR) activities, and the sperm DNA damage and sperm apoptotic markers of 262 adult males (54 Inuits from Greenland, 69 from Warsaw (Poland), 81 from Sweden, and 58 from Kharkiv (Ukraine)) exposed to different levels of POPs. Xenobiotic-induced receptor activities were determined by receptor-mediated luciferase reporter gene expression. Sperm DNA damage was measured using terminal deoxynucleotidyl transferase-driven dUTP nick labeling assay (TUNEL) and pro- (Fas) and anti-apoptotic (Bcl-xL) markers were determined by immune methods. Different features of xenobiotic-induced receptor activity in serum and sperm DNA fragmentation and apoptotic markers existed between the Inuits and the European Caucasians. Negative correlations between xenobiotic-induced receptor activities and DNA damage were found for Inuits having relatively lower xenoestrogenic, lower dioxin-like activity, and lower sperm DNA damage, but higher xenoandrogenic activity. In contrast, in the European groups, xenobiotic-induced receptor activities were found to be positively correlated with the DNA damage. Further research must elucidate whether altered receptor activities in concerted action with genetic and/or nutrient factors may have protecting effect on sperm DNA damage of the Inuit population.
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17.
  • Rignell-Hydbom, Anna, et al. (författare)
  • Dietary exposure to methyl mercury and PCB and the associations with semen parameters among Swedish fishermen.
  • 2007
  • Ingår i: Environmental Health. - 1476-069X. ; 6:14
  • Tidskriftsartikel (refereegranskat)abstract
    • Dietary POP exposure have shown negative effects on sperm motility and sperm chromatin integrity, as well as an increased proportion of Y-chromosome bearing sperms. However, it has been suggested that in epidemiological studies investigating persistent organochlorine pollutant (POP)-toxicity, other pollutants occurring simultaneously may carry an increased risk of effects, which may obscure a clear interpretation of the role of POP toxicity. One such pollutant is methyl mercury (MeHg), which has been found in fatty fish from the Baltic Sea and as a consequence men with a high consumption of such fish has been found to have twice the MeHg levels compared to men with a low fish consumption. The aim of the present study was to assess if exposure to MeHg affects male reproductive function, assessed by measuring human sperm motility, sperm concentration, total sperm count, sperm chromatin integrity and the proportion of Y-chromosome bearing sperms. Secondly we also investigated a possible interaction between MeHg and 2, 2', 4, 4', 5, 5'-hexachlorobiphenyl (CB-153), a biomarker for POP exposure, with respect to sperm outcome measures. Blood and semen samples were collected from 195 Swedish fishermen with a mean age of 47 (range 24–67 years). Blood levels of MeHg ranged from 0.11 to 16.59 μg/L (median 2.25 μg/L) and serum levels of CB-153 from 37 to 1460 ng/g lipid (median 190 ng/g lipid). The analyses revealed no association between MeHg and any of the outcomes investigated. Although men with low MeHg and high CB-153 had slightly higher DNA Fragmentation Index and fraction of Y-chromosome bearing sperms than men with low levels of both compounds, the effects were not statistically significant. In conclusion, we did not find any associations between MeHg exposure and semen quality or quantity in the dose range observed neither was any synergistic effects between MeHg and CB-153 noted.
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  • Romerius, Patrik, et al. (författare)
  • Sperm DNA Integrity in Men Treated for Childhood Cancer.
  • 2010
  • Ingår i: Clinical Cancer Research. - 1078-0432. ; Jul 1, s. 3843-3850
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: It is unknown whether childhood cancer and its treatment are associated with sperm DNA damage, which subsequently affects fertility and might be transmitted to the offspring. The aim of this study was to assess DNA fragmentation index (DFI) as an indicator of sperm DNA integrity in childhood cancer survivors (CCS), treatment regimen taken into account.EXPERIMENTAL DESIGN: In 99 CCS and 193 age-matched healthy controls, the DFI was assessed by the use of Sperm Chromatin Structure Assay.RESULTS: In the whole group of CCS DFI was increased as compared to the controls with borderline statistical significance (mean difference=0.94%; 95%CI: -0.0088; 3.7%). Those treated with radiotherapy only (mean difference=6.0%; 95%CI: 1.6; 10%) or surgery only (mean difference=2.9%; 95%CI: 0.083; 3.7%) had statistically significantly higher DFI than the controls. The odds ratio (OR) for having DFI >20%, which is associated with reduced fertility, was significantly increased in CCS as compared to the control group (OR=2.2, 95%CI: 1.1; 4.4). For the radiotherapy only group the OR was even higher (OR=4.9, 95%CI 1.3; 18). The DFI was not associated to the dose of scattered testicular irradiation or the type of chemotherapy given.CONCLUSIONS: The DFI is increased in CCS, those treated with chemotherapy being the only exception. This sperm DNA impairment may be associated with the disease per se rather than due to the treatment and may have negative consequences in terms of fertility and risk of transmission to the offspring.
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20.
  • Specht, Ina Olmer, et al. (författare)
  • Environmental Hexachlorobenzene exposure and human male reproductive function.
  • 2015
  • Ingår i: Reproductive Toxicology. - : Elsevier BV. - 1873-1708 .- 0890-6238. ; 58:Jul 22, s. 8-14
  • Tidskriftsartikel (refereegranskat)abstract
    • Hexachlorobenzene (HCB) is a persistent environmental fungicide that may disrupt androgen regulation. The aim of this study was to investigate associations between HCB levels and biomarkers of male reproductive function. 589 spouses of pregnant women from Greenland, Poland and Ukraine were enrolled between 2002 and 2004. The men provided semen and blood samples and were interviewed. HCB was measured in serum by gas chromatography. The mean serum concentrations of HCB were higher in Ukraine (182.3 ng/g lipid) and Greenland (79.0 ng/g lipid) compared to Poland (14.2 ng/g lipid). Sex Hormone Binding Globulin (SHBG) and Free Androgen Index (FAI) were associated with HCB in men from Ukraine and Poland. This study spanning large differences in environmental HCB exposure levels shows a positive association for SHBG and negative association for FAI with high serum levels of HCB in fertile men, but without major consequences for semen quality and the Inuit study population.
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  • 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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22.
  • 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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23.
  • Ståhl, Olof, et al. (författare)
  • The impact of testicular carcinoma and its treatment on sperm DNA integrity
  • 2004
  • Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 100:6, s. 1137-1144
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: In patients with testicular germ cell carcinoma (TGCC), spermatogenesis and fertility are impaired. Intracytoplasmic sperm injection has improved their possibility of fatherhood, but might also impose a risk of transmitting DNA defects to the offspring. The aim of the current study was to evaluate the impact of chemotherapy and irradiation on sperm DNA integrity.METHODS: The study included 74 patients with TGCC. Semen samples were collected before and at specific time points after patients received therapy. Sperm DNA integrity was assessed by the sperm chromatin structure assay. Controls comprised 278 military conscripts.RESULTS: There was no significant difference in the fraction of sperm with fragmented DNA (DNA fragmentation index [DFI]) between controls and patients with TGCC before postoperative cancer treatment (11% vs. 13%). Men treated with adjuvant radiotherapy had a transiently (up to 2 years) higher DFI than nontreated patients (18% vs. 13%; P = 0.03). Patients who received 1-2 cycles of adjuvant chemotherapy had a significantly lower DFI 6 months after treatment than after 1-2 years (9.1% vs. 13%; P = 0.004). Higher doses of chemotherapy among patients resulted in a significantly lower DFI compared with controls (7.3% vs. 11%; P = 0.028), which persisted throughout the 5 years of follow-up.CONCLUSIONS: Postorchiectomy, the DFI in sperm samples from patients with testicular carcinoma was at the level of controls. Radiotherapy caused a transient increase in the proportion of DFI, whereas this value decreased after chemotherapy. The biologic implications of such changes in sperm DNA after cancer therapy need to be elucidated.
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25.
  • 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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26.
  • Toft, Gunnar, et al. (författare)
  • Fertility in four regions spanning large contrasts in serum levels of widespread persistent organochlorines: a cross-sectional study
  • 2005
  • Ingår i: Environmental Health. - 1476-069X. ; 4:26
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Persistent organochlorine pollutants (POPs) may interfere with reproductive function but direct evidence in humans is very limited. METHODS: Fertility was examined in four regions with contrasting blood levels of POPs. Pregnant women and their partners in Warsaw (Poland), Kharkiv (Ukraine) and Greenland were consecutively enrolled during antenatal visits. Swedish fishermen and their spouses were recruited separately and independently of current pregnancy. Lipid adjusted serum concentrations of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (DDE) were available for both partners. Time to pregnancy interviews were obtained among 2269 women and 798 men provided a semen sample. RESULTS: Inuits had high levels of both POP markers, Swedish fishermen were high in CB-153 but low in DDE, men from Kharkiv were high in DDE and low in CB-153 while men from Warsaw were low in CB-153 and had intermediate DDE levels. Compared to Warsaw couples, fecundability was reduced among couples from Kharkiv [adjusted fecundability ratio (FR) 0.64 (95% CI 0.5-0.8)] and elevated in Swedish fishermen families [FR 1.26 (95% CI 1.0-1.6)]. Adjusted geometric means of sperm counts and morphology did not differ between regions while sperm motility was higher in men living in Warsaw. CONCLUSION: We observed regional differences in time to pregnancy and sperm motility that may be related to regional differences in POP blood levels, but other interpretations are also plausible. In particular, differences in access to safe contraception and in the prevalence of contraceptive failures are most likely to bias comparisons of time to pregnancy.
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  • Toft, Gunnar, et al. (författare)
  • Semen quality in relation to xenohormone and dioxin-like serum activity among inuits and three european populations
  • 2007
  • Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 115:SUPPL1, s. 15-20
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Semen quality in humans may be influenced by exposure to endocrine-disrupting compounds. OBJECTIVES: We analyzed associations between semen characteristics and serum xenoestrogen receptor (XER), xenoandrogen receptor (XAR), and aryl hydrocarbon receptor (AhR) transactivity. XER and XAR activity were measured in serum samples cleared for endogenous steroid hormones and AhR activity in raw lipophilic serum extracts free of proteins. RESULTS: All together, 319 men from Warsaw (Poland), Greenland, Kharkiv (Ukraine), and Sweden provided semen and blood samples. No strong and consistent associations between xenobiotic activity and semen quality measures were observed in the four populations. However, when the data were combined across populations sperm concentration increased 40% per unit increase in XER activity [95% confidence interval (CI), 1-79%] in the subgroup with XER activity below the reference level. Among subjects with XER activity above the reference level an increase of 14% (95% CI, 2-28%) was found. Furthermore, an increase of 10% motile sperm per unit increase in XER activity below reference level (95% CI, 0.2-20) was found. We are unable to exclude that the associations are chance findings. CONCLUSION: Alteration of XER, XAR, or AhR transactivity within the range found in serum from the general European and Inuit population seems not to markedly deteriorate sperm cell concentration, motility, or morphology in adult men.
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