| 1. |
- Anand-Ivell, Ravinder, et al.
(author)
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Amniotic fluid INSL3 measured during the critical time window in human pregnancy relates to cryptorchidism, hypospadias, and phthalate load : A large case-control study
- 2018
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In: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9:APR
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Journal article (peer-reviewed)abstract
- The period of the first to second trimester transition in human pregnancy represents a sensitive window for fetal organogenesis, particularly in regard to the development of the male reproductive system. This is a time of relative analytical inaccessibility. We have used a large national biobank of amniotic fluid samples collected at routine amniocentesis to determine the impacts of exogenous endocrine disruptor load on specific fetal biomarkers at this critical time. While adrenal and testicular steroids are highly correlated, they are also mostly positively influenced by increasing phthalate load, represented by the metabolites 7cx-MMeHP and 5cx-MEPP, by perfluorooctane sulfonate (PFOS) exposure, and by smoking, suggesting an adrenal stress response. In contrast, the testis specific biomarkers insulin-like peptide 3 (INSL3) and androstenedione are negatively impacted by the phthalate endocrine disruptors. Using a case-control design, we show that cryptorchidism and hypospadias are both significantly associated with increased amniotic concentration of INSL3 during gestational weeks 13-16, and some, though not all steroid biomarkers. Cases are also linked to a specifically increased variance in the Leydig cell biomarker INSL3 compared to controls, an effect exacerbated by maternal smoking. No influence of phthalate metabolites or PFOS was evident on the distribution of cases and controls. Considering that several animal and human studies have shown a negative impact of phthalate load on fetal and cord blood INSL3, respectively, the present results suggest that such endocrine disruptors may rather be altering the relative dynamics of testicular development and consequent hormone production, leading to a desynchronization of tissue organization during fetal development. Being born small for gestational age appears not to impact on the testicular biomarker INSL3 in second trimester amniotic fluid.
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| 2. |
- Andreucci, Alessandro, et al.
(author)
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Cadmium may impair prostate function as measured by Prostate Specific Antigen in semen: a cross-sectional study among European and Inuit men.
- 2015
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In: Reproductive Toxicology. - : Elsevier BV. - 1873-1708 .- 0890-6238. ; 53:Feb 3, s. 33-38
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Journal article (peer-reviewed)abstract
- We investigated the association between cadmium in blood and the concentration of the prostate specific antigen (PSA) in semen, including the modifying effects of zinc or the CAG polymorphism in the androgen receptor (AR). Blood and semen samples were collected from 504 partners of pregnant women in Greenland, Poland and Ukraine. We found an inverse trend between cadmium and PSA (log (ß)= -0.121, 95% Confidence Interval (CI):-0.213; -0.029, P=0.0103) in Greenlandic men. Similar results were observed in men with a high number of CAG repeats (CAG 24) (log (ß)=-0.231, 95% CI:-0.363; -0.098, P=0.0009). Inverse trends between cadmium and PSA were found when semen zinc concentrations were below the median value for men from Ukraine and Greenland. These outcomes suggest that cadmium may impair prostate function, as measured by PSA in semen, while high zinc levels and a low number of CAG repeats protects against this action.
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| 3. |
- Benson, Thea Emily, et al.
(author)
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Urinary bisphenol a, f and s levels and semen quality in young adult danish men
- 2021
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In: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 18:4
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Journal article (peer-reviewed)abstract
- Bisphenol A (BPA) is considered an endocrine disruptor and has been associated with deleterious effects on spermatogenesis and male fertility. Bisphenol F (BPF) and S (BPS) are struc-turally similar to BPA, but knowledge of their effects on male fertility remains limited. In this cross– sectional study, we investigated the associations between exposure to BPA, BPF, and BPS and semen quality in 556 men 18–20 years of age from the Fetal Programming of Semen Quality (FEPOS) cohort. A urine sample was collected from each participant for determination of BPA, BPF, and BPS concentrations while a semen sample was collected to determine ejaculate volume, sperm concen-tration, total sperm count, sperm motility, and sperm morphology. Associations between urinary bisphenol levels (continuous and quartile–divided) and semen characteristics were estimated using a negative binomial regression model adjusting for urine creatinine concentration, alcohol intake, smoking status, body mass index (BMI), fever, sexual abstinence time, maternal pre–pregnancy BMI, and first trimester smoking, and highest parental education during first trimester. We found no associations between urinary bisphenol of semen quality in a sample of young men from the general Danish population.
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| 4. |
- Bonde, Jens Peter, et al.
(author)
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The epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders : A systematic review and meta-analysis
- 2016
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In: Human Reproduction Update. - 1355-4786. ; 23:1, s. 104-125
-
Journal article (peer-reviewed)abstract
- BACKGROUND: More than 20 years ago, it was hypothesized that exposure to prenatal and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signaling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testicular cancer. Several consensus statements and narrative reviews in recent years have divided the scientific community and have elicited a call for systematic transparent reviews. We aimed to fill this gap in knowledge in the field of male reproductive disorders. OBJECTIVE AND RATIONALE: The aim of this study was to systematically synthesize published data on the risk of cryptorchidism, hypospadias, low sperm counts and testicular cancer following in utero or infant exposure to chemicals that have been included on the European Commission's list of Category 1 endocrine disrupting chemicals defined as having documented adverse effects due to endocrine disruption in at least one intact organism. SEARCH METHODS: A systematic literature search for original peer reviewed papers was performed in the databases PubMed and Embase to identify epidemiological studies reporting associations between the outcomes of interest and exposures documented by biochemical analyses of biospecimens including maternal blood or urine, placenta or fat tissue as well as amnion fluid, cord blood or breast milk; this was followed by meta-analysis of quantitative data. OUTCOMES: The literature search resulted in 1314 references among which we identified 33 papers(28 study populations) fulfilling the eligibility criteria. These provided 85 risk estimates of links between persistent organic pollutants and rapidly metabolized compounds (phthalates and Bisphenol A) and male reproductive disorders. The overall odds ratio (OR) across all exposures and outcomes was 1.11 (95% CI 0.91-1.35). When assessing four specific chemical subgroups with sufficient data for meta-analysis for all outcomes, we found that exposure to one of the four compounds, p,p'-DDE, was related to an elevated risk: OR 1.35 (95% CI 1.04-1.74). The data did not indicate that this increased risk was driven by any specific disorder. WIDER IMPLICATIONS: The current epidemiological evidence is compatible with a small increased risk of male reproductive disorders following prenatal and postnatal exposure to some persistent environmental chemicals classified as endocrine disruptors but the evidence is limited. Future epidemiological studies may change the weight of the evidence in either direction. No evidence of distortion due to publication bias was found, but exposure-response relationships are not evident. There are insufficient data on rapidly metabolized endocrine disruptors and on specific exposure-outcome relations. A particular data gap is evident with respect to delayed effects on semen quality and testicular cancer. Although high quality epidemiological studies are still sparse, future systematic and transparent reviews may provide pieces of evidence contributing to the narrative and weight of the evidence assessments in the field.
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| 5. |
- Bull, Cecilia, 1977, et al.
(author)
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Intra-abdominal Surgery and Intestinal Syndromes After Pelvic Radiation Therapy
- 2024
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In: ADVANCES IN RADIATION ONCOLOGY. - 2452-1094. ; 9:1
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Journal article (peer-reviewed)abstract
- Purpose: To determine the effects of intra-abdominal surgery on the intensities of 5 radiation -induced intestinal syndromes in survivors of pelvic cancer. Methods and Materials: The analysis included 623 women born in 1927 or later who had survived cancer. They all had received external radiation therapy toward the pelvic area to treat gynecologic cancers. Information from 344 women who did not undergo irradiation, matched for age and residency, was also included. Main outcome measures after the surgical procedures were the intensity scores for 5 radiation -induced intestinal syndromes: urgency-tenesmus syndrome, fecal -leakage syndrome, excessive mucus discharge, excessive gas discharge, and blood discharge. The scores were based on symptom frequencies obtained from patient -reported outcomes and on factor loadings obtained from a previously reported factor analysis. Follow-up was 2 to 15 years after radiation therapy. Results: Among survivors of cancer, intra-abdominal surgery increased the intensity of the urgency-tenesmus syndrome, the fecalleakage syndrome, excessive gas discharge, and blood discharge but had a negligible effect on mucus discharge. Intra-abdominal surgery had an especially negative effect on the urgency-tenesmus syndrome. Although the combination of appendectomy with 1 or more other intra-abdominal surgeries resulted in the highest score for all syndromes, appendectomy alone had weak to no effect. In women who did not undergo irradiation, a similar pattern was seen, albeit with much lower scores. Conclusions: We found intra-abdominal surgery to be a risk factor among survivors of gynecologic cancer, increasing the intensity score of 4 out of 5 radiation -induced intestinal syndromes. During radiation therapy, it may be worthwhile to pay extra attention to the dose of unwanted ionizing radiation to the intestines if the patient previously has undergone intra-abdominal surgery.
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| 6. |
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| 7. |
- Consales, Claudia, et al.
(author)
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Exposure to persistent organic pollutants and sperm DNA methylation changes in Arctic and European populations.
- 2016
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In: Environmental and Molecular Mutagenesis. - : Wiley. - 1098-2280 .- 0893-6692. ; 57:3, s. 200-209
-
Journal article (peer-reviewed)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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| 8. |
- Devarakonda, Sravani, et al.
(author)
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Low-grade intestinal inflammation two decades after pelvic radiotherapy.
- 2023
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In: EBioMedicine. - 2352-3964. ; 94
-
Journal article (peer-reviewed)abstract
- Radiotherapy is effective in the treatment of cancer but also causes damage to non-cancerous tissue. Pelvic radiotherapy may produce chronic and debilitating bowel symptoms, yet the underlying pathophysiology is still undefined. Most notably, although pelvic radiotherapy causes an acute intestinal inflammation there is no consensus on whether the late-phase pathophysiology contains an inflammatory component or not. To address this knowledge gap, we examined the potential presence of a chronic inflammation in mucosal biopsies from irradiated pelvic cancer survivors.We biopsied 24 cancer survivors two to 20 years after pelvic radiotherapy, and four non-irradiated controls. Using tandem mass tag (TMT) mass spectrometry and mRNA sequencing (mRNA-seq), we charted proteomic and transcriptomic profiles of the mucosal tissue previously exposed to a high or a low/no dose of radiation. Changes in the immune cell populations were determined with flow cytometry. The integrity of the protective mucus layers were determined by permeability analysis and 16S rRNA bacterial detection.942 proteins were differentially expressed in mucosa previously exposed to a high radiation dose compared to a low radiation dose. The data suggested a chronic low-grade inflammation with neutrophil activity, which was confirmed by mRNA-seq and flow cytometry and further supported by findings of a weakened mucus barrier with bacterial infiltration.Our results challenge the idea that pelvic radiotherapy causes an acute intestinal inflammation that either heals or turns fibrotic without progression to chronic inflammation. This provides a rationale for exploring novel strategies to mitigate chronic bowel symptoms in pelvic cancer survivors.This study was supported by the King Gustav V Jubilee Clinic Cancer Foundation (CB), The Adlerbertska Research Foundation (CB), The Swedish Cancer Society (GS), The Swedish State under the ALF agreement (GS and CB), Mary von Sydow's foundation (MA and VP).
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| 9. |
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| 10. |
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| 11. |
- Gaml-Sørensen, Anne, et al.
(author)
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Maternal vitamin D levels and male reproductive health : a population-based follow-up study
- 2023
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In: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 38:5, s. 469-484
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Journal article (peer-reviewed)abstract
- Maternal vitamin D levels during pregnancy may be important for reproductive health in male offspring by regulating cell proliferation and differentiation during development. We conducted a follow-up study of 827 young men from the Fetal Programming of Semen Quality (FEPOS) cohort, nested in the Danish National Birth Cohort to investigate if maternal vitamin D levels were associated with measures of reproductive health in adult sons. These included semen characteristics, testes volume, and reproductive hormone levels and were analysed according to maternal vitamin D (25(OH)D3) levels during pregnancy. In addition, an instrumental variable analysis using seasonality in sun exposure as an instrument for maternal vitamin D levels was conducted. We found that sons of mothers with vitamin D levels < 25 nmol/L had 11% (95% CI − 19 to − 2) lower testes volume and a 1.4 (95% CI 1.0 to 1.9) times higher risk of having low testes volume (< 15 mL), in addition to 20% (95% CI − 40 to 9) lower total sperm count and a 1.6 (95% CI 0.9 to 2.9) times higher risk of having a low total sperm count (< 39 million) compared with sons of mothers with vitamin D levels > 75 nmol/L. Continuous models, spline plots and an instrumental variable analysis supported these findings. Low maternal vitamin D levels were associated with lower testes volume and lower total sperm count with indications of dose-dependency. Maternal vitamin D level above 75 nmol/L during pregnancy may be beneficial for testes function in adult sons.
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| 12. |
- Gaml-Sørensen, Anne, et al.
(author)
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The estimated effect of season and vitamin D in the first trimester on pubertal timing in girls and boys : A cohort study and an instrumental variable analysis
- 2023
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In: International Journal of Epidemiology. - 0300-5771. ; 52:5, s. 1328-1340
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Journal article (peer-reviewed)abstract
- Background: Season of birth has been associated with age at menarche. Maternal vitamin D levels in pregnancy may explain this effect. We investigated whether the season of first trimester or maternal 25-hydroxyvitamin D3 [25(OH)D3] levels were associated with pubertal timing in children. Methods: We conducted a follow-up study of 15 819 children born in 2000-03 from the Puberty Cohort, nested in the Danish National Birth Cohort (DNBC). Mean differences in attaining numerous pubertal markers, including a combined estimate for the average age at attaining all pubertal markers, were estimated for low (November-April) relative to high (May-October) sunshine exposure season in the first trimester using multivariable interval-censored regression models. Moreover, we conducted a two-sample instrumental variable analysis using season as an instrument for maternal first-Trimester 25(OH)D3 plasma levels obtained from a non-overlapping subset (n = 827) in the DNBC. Results: For the combined estimate, girls and boys of mothers who had their first trimester during November-April had earlier pubertal timing than girls and boys of mothers whose first trimester occurred during May-October:-1.0 months (95% CI:-1.7 to-0.3) and-0.7 months (95% CI:-1.4 to-0.1), respectively. In the instrumental variable analysis, girls and boys also had earlier pubertal timing: respectively,-1.3 months (95% CI:-2.1 to-0.4) and-1.0 months (95% CI:-1.8 to-0.2) per SD (22 nmol/L) decrease in 25(OH)D3. Conclusions: Both first pregnancy trimester during November-April and lower 25(OH)D3 were associated with earlier pubertal timing in girls and boys.
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| 13. |
- 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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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Góralczyk, Katarzyna, et al.
(author)
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Is the fact of parenting couples cohabitation affecting the serum levels of persistent organohalogen pollutants?
- 2015
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In: International Journal of Hygiene and Environmental Health. - : Elsevier BV. - 1618-131X .- 1438-4639. ; 218:4, s. 392-400
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Journal article (peer-reviewed)abstract
- Organohalogen compounds constitute one of the important groups of persistent organic pollutants (POPs). Among them, due to their long-term health effects, one should pay attention on organochlorine pesticides, polychlorinated biphenyls (PCBs) and perfluoroalkylated substances (PFASs). This paper is an attempt to answer the question about relation between the fact of cohabitation by couples expecting a child and the level of the organohalogen compounds in the blood serum of both parents. The study was done on a population of parent couples from Greenland, Poland and Ukraine, from whom blood samples were collected in order to establish the levels of marker organohalogen compounds. We selected, as the representative of these compounds, the most persistent metabolite of DDT, i.e. p,p'-DDE, the most frequently detected PCB congener - CB-153, and PFOS and PFOA as the representatives of PFASs. The results show that in case of all compounds under study the highest concentrations were present always in men in relation to the levels detected in the blood serum of their female partners, regardless of the country of origin of the couple. A positive correlation was noted between the concentrations of the studied compounds in the blood serum of men and women in parenting couples. In some cases these correlations were statistically significant, e.g. for concentrations of p,p'-DDE in pairs from Greenland and Ukraine, of CB-153 in pairs from Poland and Ukraine, and of PFOS for parents from Greenland and Poland, while for PFOA - only for couples from Greenland. The concentrations of the compounds included in the study were similar to the levels found in general population in other countries. Our results show that the exposure to POPs resulting from cohabitation plays a role in the general exposure to these compounds.
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| 18. |
- Gotzsche, Casper R., et al.
(author)
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Combined gene overexpression of neuropeptide Y and its receptor Y5 in the hippocampus suppresses seizures
- 2012
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In: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 45:1, s. 288-296
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Journal article (peer-reviewed)abstract
- We recently demonstrated that recombinant adeno-associated viral vector-induced hippocampal overexpression of neuropeptide Y receptor, Y2, exerts a seizure-suppressant effect in kindling and kainate-induced models of epilepsy in rats. Interestingly, additional overexpression of neuropeptide Y in the hippocampus strengthened the seizure-suppressant effect of transgene Y2 receptors. Here we show for the first time that another neuropeptide Y receptor, Y5, can also be overexpressed in the hippocampus. However, unlike Y2 receptor overexpression, transgene Y5 receptors in the hippocampus had no effect on kainate-induced motor seizures in rats. However, combined overexpression of Y5 receptors and neuropeptide Y exerted prominent suppression of seizures. This seizure-suppressant effect of combination gene therapy with Y5 receptors and neuropeptide Y was significantly stronger as compared to neuropeptide Y overexpression alone. These results suggest that overexpression of Y5 receptors in combination with neuropeptide Y could be an alternative approach for more effective suppression of hippocampal seizures. (C) 2011 Elsevier Inc. All rights reserved.
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| 19. |
- Hærvig, Katia Keglberg, et al.
(author)
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Fetal exposure to maternal cigarette smoking and male reproductive function in young adulthood
- 2022
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In: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 37:5, s. 525-538
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Journal article (peer-reviewed)abstract
- Maternal smoking during pregnancy constitutes a potential, major risk factor for adult male reproductive function. In the hitherto largest longitudinal cohort, we examined biomarkers of reproductive function according to maternal smoking during the first trimester and investigated whether associations were mitigated by smoking cessation prior to the fetal masculinization programming window. Associations between exposure to maternal smoking and semen characteristics, testicular volume and reproductive hormones were assessed among 984 young men from the Fetal Programming of Semen Quality (FEPOS) cohort. Maternal smoking was assessed through interview data and measured plasma cotinine levels during pregnancy. We applied negative binomial, logistic and linear regression models to estimate differences in outcomes according to levels of maternal smoking. Sons of light smokers (≤ 10 cigarettes/day) had a 19% (95% CI − 29%, − 6%) lower sperm concentration and a 24% (95% CI − 35%, − 11%) lower total sperm count than sons of non-smokers. These estimates were 38% (95% CI − 52%, − 22%) and 33% (95% CI − 51%, − 8%), respectively, for sons of heavy smokers (> 10 cigarettes/day). The latter group also had a 25% (95% CI 1%, 54%) higher follitropin level. Similarly, sons exposed to maternal cotinine levels of > 10 ng/mL had lower sperm concentration and total sperm count. Smoking cessation prior to gestational week seven was not associated with a higher reproductive capacity. We observed substantial and consistent exposure–response associations, providing strong support for the hypothesis that maternal smoking impairs male reproductive function. This association persisted regardless of smoking cessation in early pregnancy.
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| 20. |
- Hærvig, Katia Keglberg, et al.
(author)
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Fetal exposure to paternal smoking and semen quality in the adult son
- 2020
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In: Andrology. - : Wiley. - 2047-2919 .- 2047-2927. ; 8:5, s. 1117-1125
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Journal article (peer-reviewed)abstract
- Background: The negative impact of maternal smoking during pregnancy on offspring semen quality is well established. Less is known about the impact of paternal smoking. Methods: We estimated differences in semen parameters and testicle size according to paternal smoking in 772 adult sons of women enrolled in the Danish National Birth Cohort when pregnant. Parents’ smoking was reported around gestational week 16, and analyses were adjusted for parents’ ages at conception, maternal pre-pregnancy body mass index, maternal alcohol and caffeine intake, family occupational status, ejaculatory abstinence time, clinic of semen analysis, and season. Results: Sons of smoking fathers and non-smoking mothers had a 10% (95% confidence interval: −24%, 7%) lower semen concentration and 11% (95% confidence interval: −27%, 8%) lower sperm count than sons of non-smoking parents. Having two smoking parents was associated with 19% reduction in sperm count (95% confidence interval: −37%, 3%). Paternal smoking was not associated with volume, motility, or morphology. Adjusting for maternal smoking, paternal smoking was associated with a 26% increased risk of small testicular volume (95% confidence interval: 0.89, 1.78). Discussion: Exclusion of sons with a history of testicular cancer, chemotherapy, orchiectomy, and with only one or no testicles may have caused us to underestimate associations if these men's reproductive health including semen quality are in fact more sensitive to paternal smoking. Conclusion: The study provides limited support for slightly lower sperm concentration and total sperm concentration in sons of smoking fathers, but findings are also compatible with no association.
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| 21. |
- Hærvig, Katia Keglberg, et al.
(author)
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Fetal programming of semen quality (Fepos) cohort – a dnbc male-offspring cohort
- 2020
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In: Clinical Epidemiology. - 1179-1349. ; 12, s. 757-770
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Journal article (peer-reviewed)abstract
- Background: Prenatal exposures may contribute to male infertility in adult life, but large-scale epidemiological evidence is still lacking. The Fetal Programming of Semen quality (FEPOS) cohort was founded to provide means to examine if fetal exposures can interfere with fetal reproductive development and ultimately lead to reduced semen quality and reproductive hormone imbalances in young adult men. Methods: Young adult men at least 18 years and 9 months of age born to women in the Danish National Birth Cohort living in relative proximity to Copenhagen or Aarhus and for whom a maternal blood sample and two maternal interviews during pregnancy were available were invited to FEPOS. Recruitment began in March 2017 and ended in December 2019. The participants answered a comprehensive questionnaire and underwent a physical examination where they delivered a semen, urine, and hair sample, measured their own testicular volume, and had blood drawn. Results: In total 21,623 sons fulfilled eligibility criteria of whom 5697 were invited and 1058 participated making the response rate 19%. Semen characteristics did not differ between sons from the Copenhagen and Aarhus clinics. When comparing the FEPOS semen parameters to similar cohorts, the median across all semen characteristics was slightly lower for FEPOS participants, although with smaller variation. Conclusion: With its 1058 young adult men, the FEPOS cohort is the largest population-based male-offspring cohort worldwide specifically designed to investigate prenatal determinants of semen quality. Wide-ranging information on maternal health, lifestyle, socioeconomic status, occupation, and serum concentrations of potential reproductive toxicants during pregnancy combined with biological markers of fertility in their sons collected after puberty allow for in-depth investigations of the ‘fetal origins of adult disease hypothesis’.
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| 22. |
- Hærvig, Katia Keglberg, et al.
(author)
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Maternal Exposure to Per- and Polyfluoroalkyl Substances (PFAS) and Male Reproductive Function in Young Adulthood : Combined Exposure to Seven PFAS
- 2022
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In: Environmental Health Perspectives. - 1552-9924. ; 130:10, s. 107001-107001
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Journal article (peer-reviewed)abstract
- BACKGROUND: Concerns remain about the human reproductive toxicity of the widespread per- and polyfluoroalkyl substances (PFAS) during early stages of development. OBJECTIVES: We examined associations between maternal plasma PFAS levels during early pregnancy and male offspring reproductive function in adulthood. METHODS: The study included 864 young men (age range:18.9-21.2 y) from the Fetal Programming of Semen Quality (FEPOS) cohort established between 2017 and 2019. Plasma samples from their mothers, primarily from the first trimester, were retrieved from the Danish National Biobank and levels of 15 PFAS were measured. Seven PFAS had detectable levels above the limit of detection in formula presented of the samples and were included in analyses. Semen quality, testicular volume, and levels of reproductive hormones and PFAS were assessed in the young men. We used weighted quantile sum (WQS) regression to estimate the associations between combined exposure to maternal PFAS and reproductive function, and negative binomial regression to estimate the associations of single substances, while adjusting for a range of a priori-defined fetal and postnatal risk factors. RESULTS: By a 1-unit increase in the WQS index, combined maternal PFAS exposure was associated with lower sperm concentration (formula presented ; 95% CI: formula presented ), total sperm count (formula presented ; 95% CI: formula presented ), and a higher proportion of nonprogressive and immotile sperm (5%; 95% CI: 1%, 8%) in the young men. Different PFAS contributed to the associations with varying strengths; however, perfluoroheptanoic acid was identified as the main contributor in the analyses of all three outcomes despite the low concentration. We saw no clear association between exposure to maternal PFAS and testicular volume or reproductive hormones. DISCUSSION: In a sample of young men from the general Danish population, we observed consistent inverse associations between exposure to maternal PFAS and semen quality. The study needs to be replicated in other populations, taking combined exposure, as well as emerging short-chain PFAS, into consideration. https://doi.org/10.1289/EHP10285.
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| 23. |
- Hærvig, Katia Keglberg, et al.
(author)
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Paternal pre-conceptional smoking and semen quality in the adult son
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In: Andrology. - 2047-2919.
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Journal article (peer-reviewed)abstract
- Background: Growing evidence suggests intergenerational effects of paternal pre-conceptional smoking through the germ line, but its specific impact on offspring semen quality remains uncertain because of challenges in isolating paternal exposure from maternal passive smoking or underreporting. Methods: We reran previous analyses estimating differences in semen parameters and testicular size according to paternal smoking in 867 young adult men, adding first-trimester maternal plasma cotinine to the original adjustment for maternal self-reported smoking. We also estimated differences in sperm DNA fragmentation. Paternal smoking was reported by the pregnant women around gestational week 16. Analyses were additionally adjusted for household occupational status, parental ages at birth, maternal pre-pregnancy body mass index and alcohol consumption, and abstinence time, and accounted for spillage, minutes from ejaculation to analysis, and son's own smoking. Results: We found no association between paternal preconceptional smoking and any of the semen parameters or testicular size. Adjustment for son's own smoking did not change results. Discussion: While maternal plasma cotinine offers an objective measure of tobacco exposure and allows for a more thorough adjustment of maternal smoking, the high correlation between paternal pre-conceptional smoking and maternal cotinine exposure may, have resulted in overadjustment removing some paternal effect. Inability to distinguish between paternal never smokers and former smokers, may have led to misclassification of paternal pre-conceptional smoking and underestimation of associations. Conclusion: We found no support for an independent association between paternal pre-conceptional smoking and semen quality in young adult sons, but studies with more detailed paternal smoking history are needed before firm conclusions can be drawn.
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| 24. |
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| 25. |
- Hoyer, Birgit Bjerre, et al.
(author)
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Anthropometry in 5-to 9-Year-Old Greenlandic and Ukrainian Children in Relation to Prenatal Exposure to Perfluorinated Alkyl Substances
- 2015
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In: Environmental Health Perspectives. - : Environmental Health Perspectives. - 1552-9924 .- 0091-6765. ; 123:8, s. 841-846
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Journal article (peer-reviewed)abstract
- BACKGROUND: In some animal studies, perfluorinated alkyl substances are suggested to induce weight gain. Human epidemiological studies investigating these associations are sparse. OBJECTIVE: We examined pregnancy serum concentrations of perfluorooctanoate (PFOA) and perfluoro-octane sulfonate (PFOS) and the prevalence of offspring overweight (> 1 SD) and waist-to-height ratio (WHtR) > 0.5 at 5-9 years of age. Methods: Sera from 1,022 pregnant women enrolled in the INUENDO cohort (2002-2004) from Greenland and Kharkiv (Ukraine) were analyzed for PFOA and PFOS using liquid chromatography-tandem mass spectrometry. Relative risks (RR) of being overweight and having WHtR > 0.5 in relation to continuous and categorized (tertiles) PFOA and PFOS were calculated at follow-up (2010-2012) using generalized linear models. RESULTS: Pooled PFOA median (range) was 1.3 (0.2-5.1) and PFOS median (range) was 10.8 (0.8-73.0) ng/mL. For each natural logarithm-unit (ln-unit) increase of pregnancy PFOA, the adjusted RR of offspring overweight was 1.11 [95% confidence interval (CI): 0.82, 1.53] in Greenlandic children. In Ukrainian children, the adjusted RR of offspring overweight was 1.02 (95% CI: 0.72, 1.44) for each ln-unit increase of pregnancy PFOA. Prenatal exposure to PFOS was not associated with overweight in country-specific or pooled analysis. The adjusted RR of having WHtR > 0.5 for each ln-unit increase of prenatal exposure to PFOA was 1.30 (95% CI: 0.97, 1.74) in the pooled analysis. For 1-ln-unit increase of prenatal exposure to PFOS, the adjusted RR of having a WHtR > 0.5 was 1.38 (95% CI: 1.05, 1.82) in the pooled analysis. CONCLUSIONS: The results indicate that prenatal PFOA and PFOS exposures may be associated with child waist-to-height ratio > 0.5. Prenatal PFOA and PFOS exposures were not associated with overweight.
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