Dataset Information

Urinary concentrations of phthalates in couples planning pregnancy and its association with 8-hydroxy-2'-deoxyguanosine, a biomarker of oxidative stress: longitudinal investigation of fertility and the environment study.

ABSTRACT: Oxidative stress has been recognized as one of the most important contributors to infertility in both males and females. Exposure to many environmental chemicals, such as phthalates, has been shown to induce oxidative stress. In a longitudinal study designed to assess exposure to environmental chemicals and fecundity in couples who were planning pregnancy, 894 urine samples were collected from 469 couples from Michigan and Texas during 2005-2009. The concentrations of 14 phthalate metabolites and a marker of oxidative stress, 8-hydroxy-2'-deoxyguanosine (8-OHdG), were determined in these samples. Concentrations, profiles, and estimated daily intakes (DIs) of phthalates were positively associated with 8-OHdG. The median concentrations of monomethyl phthalate (mMP), monoethyl phthalate (mEP), mono(3-carboxypropyl) phthalate (mCPP), mono-n-butyl phthalate (mBP), mono(2-isobutyl) phthalate (miBP), monobenzyl phthalate (mBzP), ?5mEHP (sum of five metabolites of di(2-ethylhexyl) phthalate (DEHP)) and ?14phthalates (sum of 14 urinary phthalate metabolites) were 0.48, 85.2, 4.50, 7.66, 4.36, 3.80, 54.8, and 249 ?g/g creatinine, respectively. The estimated DI values for DEHP in 39 individuals were above the U.S. Environmental Protection Agency's (EPA) reference dose (RfD) of 20 ?g/kg-bw/day. The mean and median concentrations of 8-OHdG were 6.02 and 3.13 ?g/g creatinine, respectively, which were significantly higher in females than in males. Statistically significant associations were found between 8-OHdG and urinary concentrations of mEP, and ?5mEHP for females. Similarly, a significant association was found between 8-OHdG and DIs estimated for select phthalates. Our results suggested that phthalate exposure increases oxidative stress, which can be a mechanism for the diminished fertility observed in couples who were highly exposed to select phthalates.

SUBMITTER: Guo Y

PROVIDER: S-EPMC4140531 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Urinary concentrations of phthalates in couples planning pregnancy and its association with 8-hydroxy-2'-deoxyguanosine, a biomarker of oxidative stress: longitudinal investigation of fertility and the environment study.

Guo Ying Y Weck Jennifer J Sundaram Rajeswari R Goldstone Alexandra E AE Louis Germaine Buck GB Kannan Kurunthachalam K

Environmental science & technology 20140808 16

Oxidative stress has been recognized as one of the most important contributors to infertility in both males and females. Exposure to many environmental chemicals, such as phthalates, has been shown to induce oxidative stress. In a longitudinal study designed to assess exposure to environmental chemicals and fecundity in couples who were planning pregnancy, 894 urine samples were collected from 469 couples from Michigan and Texas during 2005-2009. The concentrations of 14 phthalate metabolites an ...[more]

PMID: 25068827

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Project description:BACKGROUND:Use of organophosphate flame retardants (PFRs) has increased over the past decade following the phase out of some brominated flame retardants, leading to increased human exposure. We recently reported that increasing maternal PFR exposure is associated with poorer pregnancy outcomes among women from a fertility clinic. Because a small epidemiologic study previously reported an inverse association between male PFR exposures and sperm motility, we sought to examine associations of paternal urinary concentrations of PFR metabolites and their partner's pregnancy outcomes. METHODS:This analysis included 201 couples enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2005-2015) who provided one or two urine samples per IVF cycle. In both the male and female partner, we measured five urinary PFR metabolites [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), isopropylphenyl phenyl phosphate (ip-PPP), tert-butylphenyl phenyl phosphate (tb-PPP) and bis(1-chloro-2-propyl) phosphate (BCIPP)] using negative electrospray ionization liquid chromatography tandem mass spectrometry (LC-MS/MS). The sum of the molar concentrations of the urinary PFR metabolites was calculated. We used multivariable generalized linear mixed models to evaluate the association of urinary concentrations of paternal PFR metabolites with IVF outcomes, accounting for multiple in vitro fertilization (IVF) cycles per couple. Models were adjusted for year of IVF treatment cycle, primary infertility diagnosis, and maternal urinary PFR metabolites as well as paternal and maternal age, body mass index, and race/ethnicity. RESULTS:Detection rates were high for paternal urinary concentrations of BDCIPP (84%), DPHP (87%) and ip-PPP (76%) but low for tb-PPP (12%) and zero for BCIPP (0%). We observed a significant 12% decline in the proportion of fertilized oocytes from the first to second quartile of male urinary ΣPFR and a 47% decline in the number of best quality embryos from the first to third quartile of male urinary BDCIPP in our adjusted models. An 8% decline in fertilization was observed for the highest compared to lowest quartile of urinary BDCIPP concentrations (95% CI: 0.01, 0.12, p-trend=0.06). CONCLUSIONS:Using IVF as a model to investigate human reproduction and pregnancy outcomes, we found that paternal urinary concentrations of BDCIPP were associated with reduced fertilization. In contrast to previously reported findings for the female partners, the paternal urinary PFR metabolites were not associated with the proportion of cycles resulting in successful implantation, clinical pregnancy, and live birth. These results indicate that paternal preconception exposure to TDCIPP may adversely impact successful oocyte fertilization, whereas female preconception exposure to ΣPFRs may be more relevant to adverse pregnancy outcomes.

Project description:Phthalates are a class of chemicals found in a large variety of consumer products. Available experimental and limited human data show adverse effects of some phthalates on ovarian function, which has raised concerns regarding potential effects on fertility. The aim of the current study was to determine whether urinary concentrations of metabolites of phthalates and phthalate alternatives are associated with intermediate and clinical in vitro fertilization (IVF) outcomes. We enrolled 136 women undergoing IVF in a Tertiary University Affiliated Hospital. Participants provided one to two urine samples per cycle during ovarian stimulation and before oocyte retrieval. IVF outcomes were abstracted from medical records. Concentrations of 17 phthalate metabolites and two metabolites of the phthalate alternative di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) were measured. Multivariable Poisson regression models with log link were used to analyze associations between tertiles of specific gravity adjusted phthalate or DINCH metabolites and number of total oocytes, mature oocytes, fertilized oocytes, and top quality embryos. Multivariable logistic regression models were applied to evaluate the association between tertiles of specific gravity adjusted phthalate or DINCH metabolites and probability of live birth. Urinary concentrations of the sum of di-2-ethylhexyl phthalate metabolites (∑DEHP) and the individual metabolites mono-2-ethyl-5-hydroxyhexyl phthalate, mono-2-ethyl-5-oxohexyl phthalate, and mono-2-ethyl-5-carboxypentyl phthalate were negatively associated with the number of total oocytes, mature oocytes, fertilized oocytes, and top quality embryos. Of the low molecular weight phthalates, higher monoethyl phthalate and mono-n-butyl phthalate concentrations were associated with significantly fewer total, mature, and fertilized oocytes. None of the urinary phthalate metabolite concentrations were associated with a reduced probability implantation, clinical pregnancy or live birth. Metabolites of DINCH were not associated with intermediate or clinical IVF outcomes. Our results suggest that DEHP may impair early IVF outcomes, specifically oocyte parameters. Additional research is needed to elucidate the potential effect of DEHP on female fertility in the general population.

Project description:ObjectivesTo evaluate the association between the urinary 8-hydroxy-2'-deoxyguanosine (U8-OHdG) levels and the incidence of small-for-gestational age (SGA) infants and to assess the utility of U8-OHdG as a biomarker to predict the incidence of SGA infants.DesignProspective cohort study.SettingThe Japan Environment and Children's Study.ParticipantsData of participants enrolled in the Japan Environment and Children's Study, a nationwide birth cohort study, between 2011 and 2014 were analysed; 104 062 fetal records were analysed. Data of women with singleton pregnancies ≥22 weeks of gestation were analysed.Primary and secondary outcome measuresU8-OHdG levels were assessed using liquid chromatography-tandem mass spectrometry. Participants were categorised into the following three groups according to the quartile of the distribution of U8-OHdG: low U8-OHdG (<1.95 ng/mgCre), moderate U8-OHdG (the combined second and third quartiles; 1.95-2.95 ng/mgCre) and high U8-OHdG (>2.95 ng/mgCre) groups. Additionally, participants in the 90th percentile for U8-OHdG levels were analysed. Odds ratios (ORs) for SGA infants (<-1.5 and <-2.0 SD) were calculated using a logistic regression model while adjusting for confounding factors; the moderate U8-OHdG group was used as a reference. The cut-off value of U8-OHdG to predict the incidence of SGA infants was calculated using a receiver operating characteristic (ROC) curve analysis.ResultsData of 80 212 participants were analysed. The adjusted ORs for SGA infants (<-1.5 and<-2.0 SD) in the high U8-OHdG group were 1.16 (95% CI 1.07 to 1.25) and 1.22 (95% CI 1.07 to 1.38). The cut-off value of U8-OHdG (3.26 ng/mgCre) showed a poor ability to predict SGA infants (sensitivity, 21.9%; specificity, 83.6%; area under the ROC curve, 0.530).ConclusionsElevated U8-OHdG levels were associated with an increased incidence of SGA infants. However, this parameter would not be a useful screening tool for predicting SGA infants owing to its low sensitivity and specificity.

Project description:BackgroundFew epidemiologic studies have evaluated the impact of paternal environmental exposures, particularly as mixtures, on couples' pregnancy outcomes.ObjectiveWe investigated whether mixtures of paternal urinary bisphenol A (BPA), paraben, and phthalates were associated with pregnancy outcomes among couples attending a fertility center.MethodsWe included 210 couples undergoing 300 in vitro fertilization (IVF) between 2004 and 2017 in this prospective analysis. We quantified paternal urinary biomarker concentrations in one sample per cycle using isotope-dilution tandem mass spectrometry. We used principal component analysis (PCA) to identify correlations of biomarker concentrations and multivariable Cox proportional hazards models for discrete survival time to estimate the hazard ratios (HRs) and 95% CIs for the associations between PCA-derived factor scores and probability of failing to achieve a live birth. Interactions were also included in the models to examine strength of associations over three vulnerable periods [embryo transfer to implantation, implantation to clinical pregnancy, and clinical pregnancy to live birth]. Models were adjusted for paternal and maternal ages and body mass indexes, urinary dilution (specific gravity) and year of collection, infertility diagnosis, and other PCA factor scores. Sensitivity analyses with further adjustment for maternal PCA factor scores were performed.ResultsWe identified three factors, representing di-2-ethylhexyl phthalate (DEHP) metabolites, BPA and non-DEHP metabolites, and parabens, accounting for 56%, 15% and 10%, respectively, of the total variance explained. An interquartile range (25th and 75th percentiles) increase in the DEHP-related factor score was associated with elevated probability of failing prior to live birth (HR = 1.41, 95% CI: 1.08, 1.81) and the association was stronger between implantation and clinical pregnancy as well as between clinical pregnancy and live birth compared to before implantation. The overall HRs of failure for the BPA/non-DEHP-related and paraben-related factor scores were HR = 1.24 (95% CI: 0.97, 1.59) and HR = 0.99 (95% CI: 0.80, 1.24). We found similar HRs when additionally adjusting for maternal PCA factor scores.ConclusionPaternal mixtures of urinary concentrations of DEHP metabolites were related to higher infertility treatment failure.

Project description:BackgroundHepatic lipase (HL, encoded by LIPC) is a glycoprotein primarily synthesized and secreted by hepatocytes. Previous studies had demonstrated that HL is crucial for reverse cholesterol transport and affects the metabolism, composition, and level of several lipoproteins. In current study, we investigated the association of LIPC (Lipase C, Hepatic Type) variants with circulating and urinary biomarker levels by using subgroup and mediation analyses.MethodsA total of 572 participants from Taiwan were genotyped for three LIPC single nucleotide polymorphisms (SNPs) by using TaqMan assay. Fasting levels of glucose, lipid profile, inflammation markers, urine creatinine and 8-hydroxy deoxyguanosine (8-OHdG) were measured. The chi-square test, 2-sample t test and Analysis of variance (ANOVA) were used to examine differences among variables and genotype frequencies.ResultsSNPs rs2043085 and rs1532085 were significantly associated with urinary 8-OHdG levels, whereas all three SNPs were more significantly associated with Triglycerides (TG) or HDL-cholesterol (HDL-C) levels after additional adjustment for HDL-C or TG levels, respectively. Subgroup analyses revealed that the association of the LIPC SNPs with the levels of serum TG, HDL-C, and urinary 8-OHdG were predominantly observed in the men but not in the women. Differential associations of the LIPC SNPs with various lipid levels were observed in participants with different adiposity statuses. Mediation analyses indicated that TG levels acted as a suppressor masking the association of the LIPC genotypes with HDL-C levels, particularly in the men (Sobel test, all P < 0.01).ConclusionOur data revealed that interaction and suppression effects mediated the pleiotropic association of the LIPC variants. The effects of the LIPC SNPs depended on sex, adiposity status, and TG levels. Thus, our findings can provide a method for identifying high-risk populations of cardiovascular diseases for clinical diagnosis.

Project description:The secondary sex ratio (SSR), defined as the ratio of males to females at birth, has been investigated in relation to endocrine disruptors to search for environmental toxicants perturbing human sex selection. Benzophenone (BP)-type ultraviolet (UV) filters, which are used in sunscreens and personal care products, have been reported to exert estrogenic and anti-androgenic activities. This study aimed to evaluate the association between maternal, paternal, and couple urinary concentrations of BP-type UV filters and the SSR, given the absence of previous investigation. The study cohort comprised 220 couples who were enrolled in the Longitudinal Investigation of Fertility and the Environment (LIFE) Study between 2005 and 2009 prior to conception and who had a singleton birth during the follow-up period. Couples' urinary concentrations of five BP-type UV filters (ng/mL) were measured using triple-quadrupole tandem mass spectrometry: 2,4-dihydroxybenzophenone (BP-1), 2,2',4,4'-tetrahydroxybenzophenone (BP-2), 2-hydroxy-4-methoxybenzophenone (BP-3), 2,2'-dihydroxy-4-methoxybenzophenone (BP-8), and 4-hydroxybenzophenone (4-OH-BP). Modified Poisson regression models were used to estimate the relative risks (RRs) of a male birth for each BP-type UV filter, after adjusting for potential confounders. When maternal and paternal urinary BP-type UV filter concentrations were modeled jointly, both maternal BP-2 (2nd vs 1st tertile, RR, 0.62, 95% confidence interval [CI], 0.43-0.91) and paternal BP-2 (3rd vs 1st tertile, RR, 0.67, 95% CI, 0.45-0.99; p-trend, 0.04) were significantly associated with an excess of female births. Contrarily, maternal 4-OH-BP was significantly associated with an excess of male births (2nd vs 1st tertile, RR, 1.87, 95% CI, 1.27-2.74; 3rd vs 1st tertile, RR, 1.80, 95% CI, 1.13-2.87; p-trend, 0.02). Our findings provide the first evidence suggesting that BP-type UV filters may affect the SSR. However, future corroboration is needed, given the exploratory design of this study.

Dataset Information

Urinary concentrations of phthalates in couples planning pregnancy and its association with 8-hydroxy-2'-deoxyguanosine, a biomarker of oxidative stress: longitudinal investigation of fertility and the environment study.

Publications

Urinary concentrations of phthalates in couples planning pregnancy and its association with 8-hydroxy-2'-deoxyguanosine, a biomarker of oxidative stress: longitudinal investigation of fertility and the environment study.

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