| 1. |
- Björvang, Richelle D., et al.
(författare)
-
Persistent organic pollutants and the size of ovarian reserve in reproductive-aged women
- 2021
-
Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 155
-
Tidskriftsartikel (refereegranskat)abstract
- Industrial chemicals such as persistent organic pollutants (POPs) have been associated with reduced fertility in women, including longer time-to-pregnancy (TTP), higher odds for infertility, and earlier reproductive senescence. Fertility is highly dependent on the ovarian reserve, which is composed of a prenatally determined stock of non-growing follicles. The quantity and quality of the follicles decline with age, thereby eventually leading to menopause. In the clinical setting, assessing ovarian reserve directly through the histological analysis of follicular density in ovaries is not practical. Therefore, surrogate markers of ovarian reserve, such as serum anti-Müllerian hormone (AMH) are typically used. Here, we studied associations between chemical exposure and ovarian reserve in a cohort of pregnant women undergoing elective caesarean section (n = 145) in Stockholm, Sweden. Full data (histological, clinical, serum) were available for 50 women. We estimated the size of the reserve both directly by determining the density of follicles in ovarian cortical tissue samples, and indirectly by measuring AMH in associated serum samples. Concentrations of 9 organochlorine pesticides (OCPs), 10 polychlorinated biphenyls (PCBs), 3 polybrominated diphenylethers (PBDEs) and 9 perfluoroalkyl substances (PFAS) were determined in serum, and clinical data were retrieved from electronic medical records. Healthy follicle densities (median 0, range 0–193 follicles/mm3) and AMH levels (median 2.33 ng/mL, range 0.1–14.8 ng/mL) varied substantially. AMH correlated with the density of growing follicles. Twenty-three chemicals detected in more than half of the samples were included in the analyses. None of the chemicals, alone or as a mixture, correlated with AMH, growing or atretic follicles. However, HCB, transnonachlor, PCBs 74 and 99 were associated with decreased non-growing follicle densities. HCB and transnonachlor were also negatively associated with healthy follicle density. Further, mixture of lipophilic POPs (PBDE 99, p,p’-DDE, and PCB 187) was associated with lower non-growing follicle densities. In addition, exposure to HCB, p,p’-DDE, and mixture of OCPs were significantly associated with higher odds of infertility. The results suggest that exposure to chemicals may reduce the size of ovarian reserve in humans, and strongly encourage to study mechanisms behind POP-associated infertility in women in more detail.
|
|
| 2. |
- Derakhshan, Arash, et al.
(författare)
-
Association of endocrine disrupting chemicals exposure with human chorionic gonadotropin concentrations in pregnancy
- 2023
-
Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 178
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Human chorionic gonadotropin (hCG) is produced by the placenta and plays an essential role in the maintenance of pregnancy. Endocrine disrupting chemicals (EDCs) have the potential to interfere with functions related to the production and secretion of hCG; however associations between exposure to EDCs and hCG concentrations in humans remain to be elucidated. Objectives: To investigate the association of urinary, serum and plasma concentrations of EDCs during pregnancy with serum hCG concentrations. Methods: We utilized data form the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study. We investigated the association of 26 EDCs measured in early pregnancy urine or blood with serum hCG concentrations using multi-variable adjusted linear regression models per EDC and Weighted Quantile Sum (WQS) regression with repeated holdout validation for the EDCs mixture. Results: In 2,039 included women, higher exposure to bisphenol A was associated with lower hCG (beta [95% CI]: −0.06 [−0.11 to −0.002]) while higher triclosan exposure was associated with a higher hCG (0.02 [0.003 to 0.04]). Higher exposure to several phthalates, including mono-ethyl and mono-butyl phthalates (MEP and MBP) as well as metabolites of di-2-ethylhexyl phthalate (DEHP) was associated with a lower hCG (beta [95% CI] for sum of DEHP metabolites: −0.13 [−0.19 to −0.07]). Likewise, higher exposure to several polychlorinated biphenyls (PCBs) was associated with a lower hCG. In the WQS regression, each quartile increase in the EDCs mixture was associated with −0.27 lower hCG (95% CI: −0.34 to −0.19). Discussion: Higher exposure to several EDCs during pregnancy was associated with a lower hCG; and despite the small effect sizes, still indicating that the exposure may negatively affect production or secretion of hCG by the placenta. Our results provide the impetus for future experimental studies to investigate the placenta as a target organ for adverse effects of EDCs.
|
|
| 3. |
- Derakhshan, Arash, et al.
(författare)
-
Association of per- and polyfluoroalkyl substances with thyroid homeostasis during pregnancy in the SELMA study
- 2022
-
Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 167
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo investigate the association of exposure to per- and polyfluoroalkyl substances (PFAS) during early pregnancy with markers of the maternal thyroid system.MethodsSerum concentrations of seven PFAS as well as thyroid stimulating hormone (TSH), free and total thyroxine (FT4 and TT4), free and total triiodothyronine (FT3 and TT3) were measured in pregnant women in early pregnancy in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study. Outcomes were concentrations of TSH and thyroid hormones, FT4/FT3 or TT4/TT3 ratios, TSH/FT4 ratio as a marker of the negative feedback loop, TT4/FT4 or TT3/FT3 ratios as markers of the binding of thyroid hormones to binding proteins.ResultsThe study population comprised 2,008 women with median (95% range) gestational age of 10 (6–14) weeks. There was no association between PFAS and TSH. Higher PFNA, PFDA, PFHpA and PFOA levels were associated with a higher FT4 (largest effect estimate for PFDA: β [95% CI]: 0.27 [0.10 to 0.45], P = 0.002). Higher PFUnDA levels, but no other PFAS, were associated with a lower FT3 (β [95% CI]: −0.05 [-0.09 to −0.01], P = 0.005). Higher PFUnDA levels were associated with lower TT4 (β [95% CI]: −1.58 [-3.07 to −0.09]) and there was an inverted U-shaped association of PFOS with TT4 (P = 0.03). Higher PFDA, PFUnDA, PFHpA levels were associated with a lower TT3. Overall, higher PFAS concentrations were associated with a higher FT4/FT3 ratio and a higher TT4/TT3 ratio. There was no association of PFAS with the TSH/FT4 ratio. Higher concentrations of several PFAS were associated with lower TT4/FT4 and TT3/FT3 ratios.ConclusionsThese findings translate results from experimental studies suggesting that exposure to PFAS may interfere with the thyroid system during pregnancy. Further experimental studies should take into account human evidence to better understand the potential underlying mechanisms of thyroid disruption by PFAS exposure.
|
|
| 4. |
- Derakhshan, A., et al.
(författare)
-
Association of phthalate exposure with thyroid function during pregnancy
- 2021
-
Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 157
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The extent of thyroid disruptive effects of phthalates during pregnancy remains unclear. Aim: To investigate the association of maternal urinary phthalates with markers of the thyroid system during early pregnancy. Methods: Urinary concentrations of phthalate metabolites and serum concentrations of thyroid stimulating hormone (TSH), free and total thyroxine (FT4 and TT4) and free and total triiodothyronine (FT3 and TT3) were measured in pregnant women in early pregnancy in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study (2007-ongoing), a population-based prospective cohort. Results: In the 1,996 included women, higher di-ethyl-hexyl phthalate (DEHP) metabolites were associated with a lower FT4 (β [SE] for the molar sum: −0.13 [0.06], P = 0.03) and a higher TSH/FT4 ratio (0.003 [0.001], P = 0.03). Higher concentrations of di-iso-nonyl phthalate (DINP) metabolites were associated with a lower TT4 (β [SE] for the molar sum: 0.93 [0.44], P = 0.03) as well as with lower TT4/FT4 and TT4/TT3 ratios. Higher metabolites of both dibutyl and butyl-benzyl phthalate (DBP and BBzP) were associated with lower T4/T3 ratio (free and total) and higher FT4/TT4 and FT3/TT3 ratios. A higher diisononyl cyclohexane dicarboxylate (DINCH) metabolite concentration was associated with a higher TT3. Conclusions: These results translate results from experimental studies suggesting that exposure to phthalates may interfere with the thyroid system during pregnancy. This is also true for compounds that have been introduced to replace known disruptive phthalates. Further experimental studies should take into account the human evidence to better investigate the potential underlying mechanisms of thyroid disruption by phthalates.
|
|
| 5. |
- Derakhshan, A., et al.
(författare)
-
Association of urinary bisphenols and triclosan with thyroid function during early pregnancy
- 2019
-
Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 133
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Bisphenols and triclosan are considered as potential thyroid disruptors. While mild alterations in maternal thyroid function can result in adverse pregnancy and child developmental outcomes, there is still uncertainty whether bisphenols or triclosan can interfere with thyroid function during pregnancy. Objectives: We aimed to investigate the association of urinary bisphenol A (BPA), bisphenol S (BPS), bisphenol F (BPF) and triclosan with early pregnancy thyroid function. Methods: This study was embedded in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study (SELMA), a population-based prospective pregnancy cohort. In total, 1996 participants were included in the current study. Maternal urinary concentrations of three bisphenols and triclosan, collected at median (95% range) 10 (6–14) weeks of pregnancy as well as serum concentrations of thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), and total triiodothyronine (TT3) were measured. Results: Higher BPA levels were associated with lower TT4 concentrations (non-monotonic, P = 0.03), a lower FT4/FT3 ratio (β [SE] -0.02 [0.01], P = 0.03) and a lower TT4/TT3 ratio (β [SE] -0.73 [0.27], P = 0.008). Higher BPF levels were associated with a higher FT3 (β [SE] 0.01 [0.007], P = 0.04). There were no associations between other bisphenols or triclosan and absolute TSH, (F)T4 or (F)T3 concentrations. The association of BPA with thyroid function differed with gestational age. The negative association of BPA with FT4/FT3 and TT4/TT3 ratios was only apparent in early but not late gestation (P for interaction: 0.003, 0.008, respectively). Conclusion: These human data during pregnancy substantiate experimental findings suggesting that BPA could potentially affect thyroid function and deiodinase activities in early gestation.
|
|
| 6. |
- Larsson, Kristin, et al.
(författare)
-
Phthalates, non-phthalate plasticizers and bisphenols in Swedish preschool dust in relation to children's exposure
- 2017
-
Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 102, s. 114-124
-
Tidskriftsartikel (refereegranskat)abstract
- Children are exposed to a wide range of chemicals in their everyday environments, including the preschool. In this study, we evaluated the levels of phthalates, non-phthalate plasticizers and bisphenols in dust from 100 Swedish preschools and identified important exposure factors in the indoor environment. In addition, children's total exposure to these chemicals was determined by urine analysis to investigate their relation with dust exposure, and to explore the time trends by comparing with children who provided urine fifteen years earlier. The most abundant plasticizers in preschool dust were the phthalates di-isononyl phthalate (DiNP) and di-(2-ethylhexyl) phthalate (DEHP) with geometric mean levels of 450 and 266. μg/g dust, respectively, and the non-phthalate plasticizers bis(2-ethylhexyl) terephthalate (DEHT) and diisononylcyclohexane-1,2-dicarboxylate (DiNCH) found at 105 and 73. μg/g dust, respectively. The levels of several substitute plasticizers were higher in newer preschools, whereas the levels of the strictly regulated phthalate di-n-butyl phthalate (DnBP) were higher in older preschools. The presence of foam mattresses and PVC flooring in the sampling room were associated with higher levels of DiNP in dust. Children's exposure from preschool dust ingestion was below established health based reference values and the estimated exposure to different phthalates and BPA via preschool dust ingestion accounted for 2-27% of the total exposure. We found significantly lower urinary levels of BPA and metabolites of strictly regulated phthalates, but higher levels of DiNP metabolites, in urine from the children in this study compared to the children who provided urine samples fifteen years earlier.
|
|
| 7. |
- Li, Ying, et al.
(författare)
-
Determinants of serum half-lives for linear and branched perfluoroalkyl substances after long-term high exposure-A study in Ronneby, Sweden
- 2022
-
Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 163
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Per-and polyfluoroalkyl substances (PFAS) are persistent substances with surfactant and repellent properties. Municipal drinking water contaminated with PFAS had been distributed for decades to one third of households in Ronneby, Sweden. The source was firefighting foam used in a nearby airfield since the mid-1980s. Clean water was provided from December 16, 2013. Aims: The purpose was to estimate serum half-lives and their determinants in the study population for different PFAS. Methods: Up to ten blood samples were collected between 2014 and 2018 from 114 participants (age 4-84 years at entry, 53% female). 19 PFAS were analysed. Linear mixed models were used to estimate the half-lives. Results: Eight PFAS were increased in Ronneby: perfluorooctanoic acid (PFOA), perfluoropentane sulfonate (PFPeS), perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS), linear perfluorooctane sulfonate (L-PFOS) and three branched perfluorooctane sulfonates (1 m-PFOS, 3/4/5m-PFOS and 2/6m-PFOS). The mean estimated half-lives (in years) were 0.94 (95 %CI 0.86-1.02) for PFPeS, 2.47 (2.27-2.7) for PFOA, 2.67 (2.51-2.85) for 2/6m-PFOS, 2.73 (2.55-2.92) for L-PFOS, 3.43 (3.19-3.71) for 3/4/5m-PFOS, 4.52 (4.14-4.99) for PFHxS, 4.55 (4.14-5.06) for PFHpS, and 5.01 (4.56-5.55) for 1 m-PFOS. The most important determinants of a shorter half-life were young age, and better kidney function measured by estimated glomerular filtration rate and ratio of paired urine and serum PFAS levels, followed by female sex during their fertile period aged 15-50. Markers of gut inflammation and reduced permeability i.e. zonulin and calprotectin were also possibly associated with shorter half-life. The results also suggested a time-dependent PFAS elimination process, with more rapid elimination in the first year after the end of exposure. Conclusion: The half-life estimates are in line with past estimates for some PFAS such as PFOA, and the novel results for different PFOS isomers. These results provide observational support for elimination routes - renal, fecal and maternal.
|
|
| 8. |
- Mamsen, Linn Salto, et al.
(författare)
-
Concentrations of perfluoroalkyl substances (PFASs) in human embryonic and fetal organs from first, second, and third trimester pregnancies
- 2019
-
Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 124, s. 482-492
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The persistent environmental contaminants perfluoroalkyl substances (PFASs) have gained attention due to their potential adverse health effects, in particular following early life exposure. Information on human fetal exposure to PFASs is currently limited to one report on first trimester samples. There is no data available on PFAS concentrations in fetal organs throughout all three trimesters of pregnancy. Methods: We measured the concentrations of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnA), and perfluorohexane sulfonic acid (PFHxS) in human embryos and fetuses with corresponding placentas and maternal serum samples derived from elective pregnancy terminations and cases of intrauterine fetal death. A total of 78 embryos and fetuses aged 7–42 gestational weeks were included and a total of 225 fetal organs covering liver, lung, heart, central nervous system (CNS), and adipose tissue were analyzed, together with 71 placentas and 63 maternal serum samples. PFAS concentrations were assayed by liquid chromatography/triple quadrupole mass spectrometry. Results: All evaluated PFASs were detected and quantified in maternal sera, placentas and embryos/fetuses. In maternal serum samples, PFOS was detected in highest concentrations, followed by PFOA > PFNA > PFDA = PFUnA = PFHxS. Similarly, PFOS was detected in highest concentrations in embryo/fetal tissues, followed by PFOA > PFNA = PFDA = PFUnA. PFHxS was detected in very few fetuses. In general, PFAS concentrations in embryo/fetal tissue (ng/g) were lower than maternal serum (ng/ml) but similar to placenta concentrations. The total PFAS burden (i.e. the sum of all PFASs) was highest in lung tissue in first trimester samples and in liver in second and third trimester samples. The burden was lowest in CNS samples irrespective of fetal age. The placenta:maternal serum ratios of PFOS, PFOA and PFNA increased across gestation suggesting bioaccumulation in the placenta. Further, we observed that the ratios were higher in pregnancies with male fetuses compared to female fetuses. Conclusions: Human fetuses were intrinsically exposed to a mixture of PFASs throughout gestation. The compounds were detected in all analyzed tissues, suggesting that PFASs reach and may affect many types of organs. Collectively, our results demonstrate that PFASs pass the placenta and deposit to embryo and fetal tissues, calling for risk assessment of gestational exposures.
|
|
| 9. |
- Xu, Yiyi, et al.
(författare)
-
Association between serum concentrations of perfluoroalkyl substances (PFAS) and expression of serum microRNAs in a cohort highly exposed to PFAS from drinking water
- 2020
-
Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 136
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Perfluoroalkyl substances (PFAS) are widespread synthetic substances with various adverse health effects. Not much is known about the modes of action of PFAS toxicity, but one likely mechanism is alteration of microRNA expression. Objectives: To investigate whether PFAS exposure is associated with altered microRNA expression in serum. Methods: We selected women from the Ronneby cohort, with high exposure to perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS), emanating from drinking water contaminated by firefighting foam, and a control group of women from a neighbouring municipality without drinking water contamination. Serum levels of PFAS were analysed using LC/MS/MS. High coverage microRNA expression was analysed by next generation sequencing (NGS) in 53 individuals to screen for microRNAs associated with PFAS exposure. After verification by qPCR, associations between PFAS exposure and expression of 18 selected microRNAs were validated by qPCR in 232 individuals. In silico functional analyses were performed using Ingenuity pathway analysis (IPA). Results: Three microRNAs were consistently associated with PFAS exposure in the different steps of the study: miR-101-3p, miR-144-3p and miR-19a-3p (all downregulated with increasing exposure). In silico functional analyses suggested that these PFAS-associated microRNAs were annotated to e.g. cardiovascular function and disease, Alzheimer's disease, growth of cancer cell lines and cancer. Seven predicted target genes for the downregulated microRNAs were annotated to PFAS in IPA knowledge database: DNA methyltransferase 3 alpha (DNMT3 alpha), epidermal growth factor receptor (EGFR), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), nuclear receptor subfamily 1, group H, member 3 (NR1H3), peroxisome proliferator-activated receptor alpha (PPAR alpha), prostaglandin-endoperoxide synthase 2 (PTGS2), and tumour growth factor alpha (TGF alpha). Discussion: PFAS exposure was associated with downregulation of specific microRNAs. Further, in silico functional analyses suggest potential links between the specific PFAS-associated microRNAs, specific microRNA target genes and possibly also health effects.
|
|
| 10. |
- Xu, Yiyi, et al.
(författare)
-
Serum perfluoroalkyl substances in residents following long-term drinking water contamination from firefighting foam in Ronneby, Sweden.
- 2021
-
Ingår i: Environment international. - : Elsevier BV. - 1873-6750 .- 0160-4120. ; 147
-
Tidskriftsartikel (refereegranskat)abstract
- In December 2013, it was discovered that drinking water supplied to one third of the households in Ronneby, southern Sweden, was highly contaminated by PFAS (sum level >10,000 ng/L) originated from firefighting foams used at a nearby military airport.To report serum PFAS levels of Ronneby residents participating in a biomonitoring program, and to describe the variation by age, sex and calendar period for residential exposure. In addition, a reference group living in a neighboring municipality without PFAS contaminated drinking water was examined.Blood samples and demographic data were collected for 3297 Ronneby residents and 226 individuals from the reference group. Yearly residence addresses were available for 3086 Ronneby residents from the national population registry. Serum concentrations of PFHxS, PFOS and PFOA were determined in all participants, with additional PFHpA, PFNA and PFDA in subsets of the participants.The population geometric means for serum PFHxS, PFOS and PFOA were 114, 135 and 6.8 ng/mL for all Ronneby residents, i.e.135, 35 and 4.5 times higher than for the reference group. Ronneby residents who resided in the area with contaminated water supply during 2005-2013 showed much higher PFAS levels in 2014 than those exposed only before 2005. Ronneby residents who never resided in the area with contaminated water supply also had higher serum PFAS levels than the reference group. All three PFAS were highly correlated (rs > 0.9 for each pair). Serum PFAS levels were lowest in teenage years and then increased with age. Adult females had lower PFAS levels on average than males under the age of 60 but higher above 60.The results reveal high serum PFAS levels dominated by PFHxS and PFOS in the Ronneby residents highly exposed to PFAS originated from firefighting foams. The PFAS exposure in Ronneby permits studies of associations to a range of health parameters, as well as studies of the toxicokinetics of PFAS exposure.
|
|
