| 1. |
- Tobi, Elmar W., et al.
(författare)
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DNA methylation differences at birth after conception through ART
- 2021
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Ingår i: Human Reproduction. - : Oxford University Press. - 0268-1161 .- 1460-2350. ; 36:1, s. 248-259
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION: Is there a relation between ART and DNA methylation (DNAm) patterns in cord blood, including any differences between IVF and ICSI?SUMMARY ANSWER: DNAm at 19 CpGs was associated with conception via ART, with no difference found between IVF and ICSI.WHAT IS KNOWN ALREADY: Prior studies on either IVF or ICSI show conflicting outcomes, as both widespread effects on DNAm and highly localized associations have been reported. No study on both IVF and ICSI and genome-wide neonatal DNAm has been performed.STUDY DESIGN, SIZE, DURATION: This was a cross-sectional study comprising 87 infants conceived with IVF or ICSI and 70 conceived following medically unassisted conception. The requirement for inclusion in the study was an understanding of the Swedish language and exclusion was the use of donor gametes.PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were from the UppstART study, which was recruited from fertility and reproductive health clinics, and the Born into Life cohort, which is recruited from the larger LifeGene study. We measured DNAm from DNA extracted from cord blood collected at birth using a micro-array (450k array). Group differences in DNAm at individual CpG dinucleotides (CpGs) were determined using robust linear models and post-hoc Tukey's tests.MAIN RESULTS AND THE ROLE OF CHANCE: We found no association of ART conception with global methylation levels, imprinted loci and meta-stable epialleles. In contrast, we identify 19 CpGs at which DNAm was associated with being conceived via ART (effect estimates: 0.5-4.9%, P-FDR < 0.05), but no difference was found between IVF and ICSI. The associated CpGs map to genes related to brain function/development or genes connected to the plethora of conditions linked to subfertility, but functional annotation did not point to any likely functional consequences.LIMITATIONS, REASONS FOR CAUTION: We measured DNAm in cord blood and not at later ages or in other tissues. Given the number of tests performed, our study power is limited and the findings need to be replicated in an independent study.WIDER IMPLICATIONS OF THE FINDINGS: We find that ART is associated with DNAm differences in cord blood when compared to non-ART samples, but these differences are limited in number and effect size and have unknown functional consequences in adult blood. We did not find indications of differences between IVF and ICSI.
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| 2. |
- Anders, Larsson, et al.
(författare)
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Higher levels of Hepatocyte Growth Factor (HGF) in human seminal plasma in comparison with blood plasma and negative association with several motile sperm cells
- 2023
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Ingår i: Global Journal of Fertility and Research. - 2640-7884. ; 8:1, s. 008-013
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Tidskriftsartikel (refereegranskat)abstract
- Context: Semen is a complex fluid with many functions, some of them well-known, others more obscure.Aims: The aim of this study was to investigate the levels of Hepatocyte Growth Factor (HGF) in human seminal plasma in comparison with blood plasma levels.Methods: HGF concentrations were measured in seminal plasma from 40 men utilizing commercial ELISA kits. Blood plasma from 40 healthy blood donors served as a comparison group.Results: Median seminal plasma HGF was approximately five times higher than the levels found in blood plasma (5717.5 pg/mL vs. 1124.6 pg/mL). There was a negative correlation between HGF values in seminal plasma and the number of sperm cells.Conclusion: The study shows that seminal plasma contains high levels of HGF and that HGF binds to prostasomes. Male HGF can thus reach the female reproductive tract during unprotected sexual intercourse. Further studies are warranted to evaluate the effect of this on fertility.
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| 3. |
- Bellavia, Andrea, et al.
(författare)
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Association between chemical mixtures and female fertility in women undergoing assisted reproduction in Sweden and Estonia
- 2023
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Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 216:Part 1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Women of reproductive age are exposed to ubiquitous chemicals such as phthalates, parabens, and per -and polyfluoroalkyl substances (PFAS), which have potential endocrine disrupting properties and might affect fertility. Our objective was to investigate associations between potential endocrine-disrupting chemicals (EDCs) and female fertility in two cohorts of women attending fertility clinics.Methods: In a total population of 333 women in Sweden and Estonia, we studied the associations between chemicals and female fertility, evaluating ovarian sensitivity index (OSI) as an indicator of ovarian response, as well as clinical pregnancy and live birth from fresh and frozen embryo transfers. We measured 59 chemicals in follicular fluid samples and detected 3 phthalate metabolites, di-2-ethylhexyl phthalate (DEHP) metabolites, 1 paraben, and 6 PFAS in > 90% of the women. Associations were evaluated using multivariable-adjusted linear or logistic regression, categorizing EDCs into quartiles of their distributions, as well as with Bayesian Kernel Ma-chine Regression.Results: We observed statistically significant lower OSI at higher concentrations of the sum of DEHP metabolites in the Swedish cohort (Q4 vs Q1, beta =-0.21, 95% CI:-0.38,-0.05) and methylparaben in the Estonian cohort (Q3 vs Q1, beta =-0.22, 95% CI:-0.44,-0.01). Signals of potential associations were also observed at higher concentrations of PFUnDA in both the combined population (Q2 vs. Q1,beta =-0.16, 95% CI-0.31,-0.02) and the Estonian population (Q2 vs. Q1,beta =-0.27, 95% CI-0.45,-0.08), and for PFOA in the Estonian population (Q4 vs. Q1, beta =-0.31, 95% CI-0.61,-0.01). Associations of chemicals with clinical pregnancy and live birth presented wide confidence intervals.Conclusions: Within a large chemical mixture, we observed significant inverse associations levels of DEHP me-tabolites and methylparaben, and possibly PFUnDA and PFOA, with OSI, suggesting that these chemicals may contribute to altered ovarian function and infertility in women.
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| 4. |
- Bjorvang, Richelle D., et al.
(författare)
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Follicular fluid and blood levels of persistent organic pollutants and reproductive outcomes among women undergoing assisted reproductive technologies
- 2022
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Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 208
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Tidskriftsartikel (refereegranskat)abstract
- Persistent organic pollutants (POPs) are industrial chemicals resistant to degradation and have been shown to have adverse effects on reproductive health in wildlife and humans. Although regulations have reduced their levels, they are still ubiquitously present and pose a global concern. Here, we studied a cohort of 185 women aged 21-43 years with a median of 2 years of infertility who were seeking assisted reproductive technology (ART) treatment at the Carl von Linne Clinic in Uppsala, Sweden. We analyzed the levels of 9 organochlorine pesticides (OCPs), 10 polychlorinated biphenyls (PCBs), 3 polybrominated diphenyl ethers (PBDEs), and 8 perfluoroalkyl substances (PFASs) in the blood and follicular fluid (FF) samples collected during ovum pick-up. Impact of age on chemical transfer from blood to FF was analyzed. Associations of chemicals, both individually and as a mixture, to 10 ART endpoints were investigated using linear, logistic, and weighted quantile sum regression, adjusted for age, body mass index, parity, fatty fish intake and cause of infertility. Out of the 30 chemicals, 20 were detected in more than half of the blood samples and 15 in FF. Chemical transfer from blood to FF increased with age. Chemical groups in blood crossed the blood-follicle barrier at different rates: OCPs > PCBs > PFASs. Hexachlorobenzene, an OCP, was associated with lower anti-Miillerian hormone, clinical pregnancy, and live birth. PCBs and PFASs were associated with higher antral follicle count and ovarian response as measured by ovarian sensitivity index, but also with lower embryo quality. As a mixture, similar findings were seen for the sum of PCBs and PFASs. Our results suggest that age plays a role in the chemical transfer from blood to FF and that exposure to POPs significantly associates with ART outcomes. We strongly encourage further studies to elucidate the underlying mechanisms of reproductive effects of POPs in humans.
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| 5. |
- Hallberg, Ida, et al.
(författare)
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Associations between lifestyle factors and levels of per- and polyfluoroalkyl substances (PFASs), phthalates and parabens in follicular fluid in women undergoing fertility treatment
- 2023
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Ingår i: Journal of Exposure Science and Environmental Epidemiology. - : Springer Nature. - 1559-0631 .- 1559-064X. ; 33, s. 699-709
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Tidskriftsartikel (refereegranskat)abstract
- Background: Concerns have been raised whether exposure to endocrine-disrupting chemicals (EDCs) can alter reproductive functions and play a role in the aetiology of infertility in women. With increasing evidence of adverse effects, information on factors associated with exposure is necessary to form firm recommendations aiming at reducing exposure.Objective: Our aim was to identify associations between lifestyle factors including the home environment, use of personal care products (PCP), and dietary habits and concentrations of EDCs in ovarian follicular fluid.Methods: April-June 2016, 185 women undergoing ovum pick-up for in vitro fertilisation in Sweden were recruited. Correlation analyses were performed between self-reported lifestyle factors and concentration of EDCs analysed in follicular fluid. Habits related to cleaning, PCPs, and diet were assessed together with concentration of six per- and polyfluoroalkyl substances (PFASs) [PFHxS, PFOA, PFOS, PFNA, PFDA and PFUnDA], methyl paraben and eight phthalate metabolites [MECPP, MEHPP, MEOHP, MEHP, cxMinCH, cxMiNP, ohMiNP, MEP, MOHiBP]. Spearman's partial correlations were adjusted for age, parity and BMI.Results: Significant associations were discovered between multiple lifestyle factors and concentrations of EDCs in ovarian follicular fluid. After correcting p values for multiple testing, frequent use of perfume was associated with MEP (correlation rho = 0.41 (confidence interval 0.21-0.47), p < 0.001); hens' egg consumption was positively associated with PFOS (rho = 0.30 (0.15-0.43), p = 0.007) and PFUnDA (rho = 0.27 (0.12-0.40), p = 0.036). White fish consumption was positively associated with PFUnDA (rho = 0.34 (0.20-0.47), p < 0.001) and PFDA (rho = 0.27 (0.13-0.41), p = 0.028). More correlations were discovered when considering the raw uncorrected p values. Altogether, our results suggest that multiple lifestyle variables affect chemical contamination of follicular fluid.Impact statement: This study shows how lifestyle factors correlate with the level of contamination in the ovary by both persistent and semi-persistent chemicals in women of reproductive age. Subsequently, these data can be used to form recommendations regarding lifestyle to mitigate possible negative health outcomes and fertility problems associated with chemical exposure, and to inform chemical policy decision making. Our study can also help form the basis for the design of larger observational and intervention studies to examine possible effects of lifestyle changes on exposure levels, and to unravel the complex interactions between biological factors, lifestyle and chemical exposures in more detail.
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| 6. |
- Hallberg, Ida, et al.
(författare)
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Suspect and non-target screening of ovarian follicular fluid and serum : identification of anthropogenic chemicals and investigation of their association to fertility
- 2021
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Ingår i: Environmental Science. - : Royal Society of Chemistry. - 2050-7887 .- 2050-7895. ; 23:10, s. 1578-1588
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Tidskriftsartikel (refereegranskat)abstract
- In this work, ultra-high performance liquid chromatography-high resolution (Orbitrap) mass spectrometry-based suspect and non-target screening was applied to follicular fluid (n = 161) and serum (n = 116) from women undergoing in vitro fertilization in order to identify substances that may be associated with decreased fertility. Detected features were prioritized for identification based on (i) hazard/exposure scores in a database of chemicals on the Swedish market and an in-house database on per- and polyfluoroalkyl substances (PFAS); (ii) enrichment in follicular fluid relative to serum; and (iii) association with treatment outcomes. Non-target screening detected 20 644 features in follicular fluid and 13 740 in serum. Two hundred and sixty-two features accumulated in follicular fluid (follicular fluid: serum ratio >20) and another 252 features were associated with embryo quality. Standards were used to confirm the identities of 21 compounds, including 11 PFAS. 6-Hydroxyindole was associated with lower embryo quality and 4-aminophenol was associated with higher embryo quality. Overall, we show the complexity of follicular fluid and the applicability of suspect and non-target screening for discovering both anthropogenic and endogenous substances, which may play a role in fertility in women.
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| 7. |
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| 8. |
- Schölin Bywall, Karin, et al.
(författare)
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Would you consider donating your left-over embryos to treat Parkinson’s disease? : Interviews with individuals that underwent IVF in Sweden
- 2022
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Ingår i: BMC Medical Ethics. - : Springer Science and Business Media LLC. - 1472-6939. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundParkinson’s disease (PD) has been considered to be one of the most promising target diseases for forthcoming cell-based therapy. The aim of this study is to explore the views of individuals with cryopreserved embryos on using human embryonic stem cells for treating PD.MethodsThe study was performed as a qualitative, semi-structured interview study in June–October 2020. Participants were recruited at a private fertility clinic located in one of the larger Swedish cities. The clinic provides both publicly financed and privately financed IVF-treatments. All interviews were performed by telephone and analyzed using thematic content analysis. Five main categories emerged from 27 sub-categories.ResultsIn total, 18 interviews were performed with 22 individuals, as either a couple (n = 16) or separately (n = 6). Participants had different views on what a cryopreserved embryo is. Some participants addressed cryopreserved embryos as ‘a lump of cells’, and some in terms of their ‘unborn child’. Conditions for donation of cryopreserved embryos for cell-based treatment in PD were: not losing control of what is happening to the embryo, that donating must be voluntary and based on informed consent with time for reflection, that reimbursement, equality and transparency.ConclusionsUsing cryopreserved embryos to treat PD is associated with fundamental ethical and practical issues. This study shows that IVF couples with left-over embryos may be supportive but there is a need for future research to assess people’s views on using cryopreserved embryos for cell-based treatment in PD on a more aggregated level.
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| 9. |
- Sveen, Kari Anne, et al.
(författare)
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Autoantibodies against methylglyoxal-modified apolipoprotein B100 and apob100 peptide are associated with less coronary artery atherosclerosis and retinopathy in long-term type 1 diabetes
- 2021
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 44:6, s. 1402-1409
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Methylglyoxal (MGO), a reactive aldehyde forming advanced glycation end products (AGEs), is increased in diabetes and recognized by the immune system, resulting in anti-AGE-specific autoantibodies. The association of these immune responses with macro- and microvascular complications in type 1 diabetes remains unclarified. We investigated associations between MGO-modified apolipoprotein B100 (apoB100) and apoB100 peptide 5 (MGO-p5) autoantibodies and coronary atherosclerosis and retinopathy in type 1 diabetes. RESEARCH DESIGN AND METHODS IgM and IgG against MGO-apoB100 and MGO-p5 were measured by ELISA in plasma from 103 subjects with type 1 diabetes and 63 control subjects (Dialong study) and in a replication cohort of 27 subjects with type 1 diabetes (Oslo study). Coronary atherosclerosis was assessed by computed tomography coronary angiography or intravascular ultrasound. Retinopathy was classified by retinal photos. RESULTS MGO-apoB100 IgM and MGO-p5 IgM levels were higher in subjects with diabetes with no coronary artery stenosis compared with subjects with significant stenosis (median [interquartile range]: 96.2 arbitrary units [AU] [71-126.8] vs. 54 AU [36.1-85.4], P 5 0.003 for MGO-apoB100; and 77.4 AU [58-106] vs. 36.9 AU [28.9-57.4], P 5 0.005 for MGO-p5). MGO-apoB100 IgM and MGO-p5 IgM were associated with less severe coronary stenosis after adjusting for confounders (odds ratio 0.2 [95% CI 0.05-0.6], P 5 0.01; and 0.22 [0.06-0.75], P 5 0.02). The inverse association of MGO-p5 IgM and coronary stenosis was confirmed in the replication cohort. Subjects with proliferative retinopathy had significantly lower MGO-apoB100 IgM and MGO-p5 IgM than those with background retinopathy. CONCLUSIONS Autoantibodies against AGE-modified apoB100 are inversely associated with coronary atherosclerosis and proliferative retinopathy, suggesting vascular protective effects of these autoantibodies in type 1 diabetes.
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