| 1. |
- Thomsen, Anne Marie L., et al.
(författare)
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Female exposure to phthalates and time to pregnancy : A first pregnancy planner study
- 2017
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 32:1, s. 232-238
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION Is female exposure to phthalate metabolites associated with reduced fecundity, as estimated by prolonged time to pregnancy (TTP)? SUMMARY ANSWER Female exposure to monoethyl phthalate (MEP) but not monobutyl phthalate (MBP), monobenzyl phthalate (MBzP) and monoethylhexyl phthalate (MEHP) was associated with a longer TTP. WHAT IS KNOWN ALREADY Male exposure to phthalates is potentially associated with adverse effects on human fecundity in epidemiological studies, but little is known about the potential effects on female reproduction. STUDY DESIGN SIZE AND DURATION A cohort study with prospective data based on 229 women from a Danish cohort of 430 first pregnancy planning couples enrolled in 1992-1994. In 2009, urinary analyses of phthalate metabolites were performed on stored urine samples from this cohort. PARTICIPANTS/MATERIALS, SETTING AND METHODS We analyzed MEP, MBP, MBzP and MEHP in female morning spot urine samples collected daily during the first 10 days of menstrual cycles after discontinuation of contraception. The exposure assessment was based on the mean of two measurements from each woman collected in a period of 6 menstrual cycles. We used Cox regression with discrete time to estimate fecundability ratios (FRs) and 95% CI in relation to the average urine metabolite concentration exposure level, controlled for age and BMI, and the time-varying variables smoking and alcohol. MAIN RESULT AND ROLE OF CHANCE Urinary concentration of MEP was associated with a decreased fecundity (adjusted FR 0.79; 95% CI: 0.63; 0.99) corresponding to a 21% decreased probability of conception for each natural log (ln) unit increase in MEP. No significant association with TTP was found for MBP, MBzP and MEHP. LIMITATIONS REASONS FOR CAUTION Subfertile women were overrepresented in the study population due to exclusion of 77 high fertile women who became pregnant in the first cycle when urine collection began. WIDER IMPLICATIONS OF THE FINDINGS Our results suggest that female exposure to MEP may have an adverse effect on female fecundity, but these findings need to be replicated in a larger and newer cohort study with sufficient exposure contrast if the use of diethyl phthalate (DEP) and thereby MEP in the future potentially should be regulated in cosmetics and industrial consumer products.
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| 2. |
- Lenters, Virissa, et al.
(författare)
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Prenatal phthalate, perfluoroalkyl acid, and organochlorine exposures and term birth weight in three birth cohorts : Multi-pollutant models based on elastic net regression
- 2016
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 124:3, s. 365-372
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Tidskriftsartikel (refereegranskat)abstract
- Background: Some legacy and emerging environmental contaminants are suspected risk factors for intrauterine growth restriction. However, the evidence is equivocal, in part due to difficulties in disentangling the effects of mixtures. Objectives: We assessed associations between multiple correlated biomarkers of environmental exposure and birth weight. Methods: We evaluated a cohort of 1,250 term (≥ 37 weeks gestation) singleton infants, born to 513 mothers from Greenland, 180 from Poland, and 557 from Ukraine, who were recruited during antenatal care visits in 2002‒2004. Secondary metabolites of diethylhexyl and diisononyl phthalates (DEHP, DiNP), eight perfluoroalkyl acids, and organochlorines (PCB-153 and p,p´‑DDE) were quantifiable in 72‒100% of maternal serum samples. We assessed associations between exposures and term birth weight, adjusting for co-exposures and covariates, including prepregnancy body mass index. To identify independent associations, we applied the elastic net penalty to linear regression models. Results: Two phthalate metabolites (MEHHP, MOiNP), perfluorooctanoic acid (PFOA), and p,p´-DDE were most consistently predictive of term birth weight based on elastic net penalty regression. In an adjusted, unpenalized regression model of the four exposures, 2-SD increases in natural log–transformed MEHHP, PFOA, and p,p´-DDE were associated with lower birth weight: –87 g (95% CI: –137, –340 per 1.70 ng/mL), –43 g (95% CI: –108, 23 per 1.18 ng/mL), and –135 g (95% CI: –192, –78 per 1.82 ng/g lipid), respectively; and MOiNP was associated with higher birth weight (46 g; 95% CI: –5, 97 per 2.22 ng/mL). Conclusions: This study suggests that several of the environmental contaminants, belonging to three chemical classes, may be independently associated with impaired fetal growth. These results warrant follow-up in other cohorts.
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| 3. |
- Anand-Ivell, Ravinder, et al.
(författare)
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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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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9:APR
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Benson, Thea Emily, et al.
(författare)
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Urinary bisphenol a, f and s levels and semen quality in young adult danish men
- 2021
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 18:4
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Jørgensen, Kristian T., et al.
(författare)
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Perfluoroalkyl substances and time to pregnancy in couples from Greenland, Poland and Ukraine
- 2014
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Ingår i: Environmental Health: A Global Access Science Source. - 1476-069X. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Perfluoroalkyl substances (PFAS) are suggested to affect human fecundity through longer time to pregnancy (TTP). We studied the relationship between four abundant PFAS and TTP in pregnant women from Greenland, Poland and Ukraine representing varying PFAS exposures and pregnancy planning behaviors. Methods: We measured serum levels of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) in 938 women from Greenland (448 women), Poland (203 women) and Ukraine (287 women). PFAS exposure was assessed on a continuous logarithm transformed scale and in country-specific tertiles. We used Cox discrete-time models and logistic regression to estimate fecundability ratios (FRs) and infertility (TTP >13 months) odds ratios (ORs), respectively, and 95% confidence intervals (CI) according to PFAS levels. Adjusted analyses of the association between PFAS and TTP were done for each study population and in a pooled sample. Results: Higher PFNA levels were associated with longer TTP in the pooled sample (log-scale FR∈=∈0.80; 95% CI 0.69-0.94) and specifically in women from Greenland (log-scale FR∈=∈0.72; 95% CI 0.58-0.89). ORs for infertility were also increased in the pooled sample (log-scale OR∈=∈1.53; 95% CI 1.08-2.15) and in women from Greenland (log-scale OR∈=∈1.97; 95% CI 1.22-3.19). However, in a sensitivity analysis of primiparous women these associations could not be replicated. Associations with PFNA were weaker for women from Poland and Ukraine. PFOS, PFOA and PFHxS were not consistently associated with TTP. Conclusions: Findings do not provide consistent evidence that environmental exposure to PFAS is impairing female fecundity by delaying time taken to conceive.
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| 6. |
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| 7. |
- Toft, Gunnar, et al.
(författare)
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Association between Pregnancy Loss and Urinary Phthalate Levels around the Time of Conception
- 2012
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 1552-9924 .- 0091-6765. ; 120:3, s. 458-463
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Animal studies indicate that some phthalate metabolites may harm female reproductive function. OBJECTIVES: We assessed the associations between exposure to phthalate metabolites and pregnancy loss. METHODS: Using a previously established cohort of couples planning their first pregnancy, we analyzed four primary and two oxidized secondary phthalate metabolites in urine samples collected on day 10 after the first day of the last menstrual period before conception occurred (n = 128) and during the previous cycle (if any, is = 111). Subclinical embryonal loss was identified by repeated measurement of urinary human chorionic gonadotropin, and information on clinical spontaneous abortions was obtained by telephone interview with the mother. RESULTS: Pregnancy loss (n = 48) was increased among women with urinary concentration of monoethylhexyl phthalate (MEHP) in the upper tertile in the conception sample compared with women in the lowest tertile [adjusted odds ratio (OR) = 2.9; 95% confidence interval (CI): 1.1, 7.6]. The corresponding OR for subclinical embryonal loss (n = 32) was 40.7 (95% Cl: 4.5, 369.5). CONCLUSIONS: The phthalate metabolite MEHP was associated with higher occurrence of pregnancy loss. Because this is the first human study to show this association and the sample size is small, the findings need to be corroborated in independent studies.
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