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Altered blood proteome in girls with high urine concentrations of bisphenol a, genistein, mono-ethyl hexylphthalate and mono-benzyl phthalate.

ABSTRACT: Children exposed to endocrine disruptors are hypothesized to be susceptible for cancer development later in life. Identifying functional biomarkers of specific exposures may indicate predisposition for this disease. The objectives of this study were to identify protein biomarkers of 1) effect and 2) susceptibility for cancer from the blood of girls exposed to select environmental chemicals. In prepubertal girls, urine concentrations of bisphenol A (BPA), genistein, mono-ethyl hexylphthalate (MEHP) and mono-benzyl phthalate (MBzP) were used to identify girls in the top quintile of exposure for each of these environmental chemicals, and age-matched prepubertal girls with urine analyte concentrations below the median. Blood samples of these girls were depleted of the seven most abundant proteins using human-specific affinity spin columns. Using isobaric Tandem Mass Tags and quantitative mass spectrometry (TMT-MS), 51, 34, 57 and 47 differentially expressed proteins were identified from the blood of prepubertal girls with high urine concentrations of BPA, genistein, MEHP and MBzP, respectively, compared to controls. The data demonstrates the potential of proteomic technology to not only provide biomarkers of effect from aminimally invasive source of biological material, blood, but to identify protein molecules that are intimately involved in the pathobiology of cancer. The differentially regulated cancer associated proteins in girls with high concentrations of BPA and genistein are consistent with reported roles of BPA in carcinogenesis and of genistein in mammary cancer prevention, respectively.

SUBMITTER: Wang J

PROVIDER: S-EPMC6663097 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Altered blood proteome in girls with high urine concentrations of bisphenol a, genistein, mono-ethyl hexylphthalate and mono-benzyl phthalate.

Wang Jun J Betancourt Angela A Jenkins Sarah S Biro Frank F Pinney Susan M SM Chen Dongquan D Russo Jose J Lamartiniere Coral A CA

MOJ proteomics & bioinformatics 20150310 2

Children exposed to endocrine disruptors are hypothesized to be susceptible for cancer development later in life. Identifying functional biomarkers of specific exposures may indicate predisposition for this disease. The objectives of this study were to identify protein biomarkers of 1) effect and 2) susceptibility for cancer from the blood of girls exposed to select environmental chemicals. In prepubertal girls, urine concentrations of bisphenol A (BPA), genistein, mono-ethyl hexylphthalate (MEH ...[more]

PMID: 31360934

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Project description:BackgroundInsufficient or excessive gestational weight gain are associated with increased risks of adverse birth and childhood outcomes. Increasing evidence suggests that exposure to bisphenols and phthalates may disrupt hormonal pathways and thereby influence gestational weight gain.ObjectiveTo examine the associations of early and mid-pregnancy bisphenol and phthalate urine concentrations with gestational weight gain.MethodsIn a population-based prospective cohort study among 1,213 pregnant women, we measured early and mid-pregnancy bisphenol and phthalate urine concentrations. Maternal anthropometrics before pregnancy were obtained by questionnaire and repeatedly measured at our research center during pregnancy. We used linear and logistic regressions to evaluate the associations of bisphenols and phthalates with total and period-specific gestational weight gain.ResultsHigher maternal total bisphenols and bisphenol S were associated with a lower total gestational weight gain at nominal level. Stratification by body mass index group showed that higher total bisphenols and bisphenol S were associated with lower total gestational weight gain specifically in normal weight women (respectively -509 g [95% CI -819, -198] and -398 g [95% CI -627, -169]). Each log unit increase in early pregnancy total bisphenol and bisphenol A urine concentrations were associated with lower mid- to late pregnancy gestational weight gain in the whole group (effect estimates -218 g/log unit increase [95% CI -334, -102] and -132 g/log unit increase [95% CI -231, -34], respectively). These associations were independent of mid-pregnancy compounds. Mid-pregnancy bisphenols and phthalates concentrations were not associated with gestational weight gain.DiscussionHigher maternal bisphenol urine concentrations in early pregnancy may lead to reduced gestational weight in second half of pregnancy. Further research is needed to assess the effects of maternal bisphenols and phthalates urine concentrations on placental and fetal growth and development.

Project description:BACKGROUND:Phthalates and bisphenol A (BPA) are environmental contaminants that may affect early embryonic development. OBJECTIVE:To assess the association between phthalate metabolites and BPA with early pregnancy endpoints in a cohort of women followed from before conception. METHODS:We quantified 11 phthalate metabolites and BPA in 137 conception cycles from naturally conceived clinical pregnancies. Phthalate metabolites and BPA concentrations were measured in a pooled sample of three daily morning urine specimens. Daily urinary hormone measurements had previously been used to define ovulation, implantation, and corpus luteum rescue. We assessed associations between conception cycle exposures (phthalate biomarkers and BPA) and 1) time from ovulation to implantation; 2) type of corpus luteum rescue (timing and pattern of rise in progesterone: early, late, or no rise); and 3) rate of initial rise in hCG. RESULTS:Mono(3-carboxypropyl) phthalate (MCPP) and mono-isobutyl phthalate (MiBP) were associated with earlier implantation (6-8 days vs. 9 days (the most commonly observed); per natural log-unit, OR (95% CI) =?2.8 (1.2, 6.7) and OR (CI) =?2.1 (1.2, 3.7), respectively). Monoethyl phthalate (MEP) was associated with later implantation (10-12 days vs. 9 days); OR (CI) =?1.5 (1.0, 2.1). Compared with implantation on day 9, BPA was significantly associated with both earlier and later implantation (OR=2.2 for both). Women with concentrations above the median of monobenzyl phthalate (MBzP) (p?=?0.04) or above the median of the molar sum of four di(2-ethylhexyl) phthalate metabolites (?DEHP) (p?=?0.08) had a slower initial rise in hCG. Increasing MCPP was associated with an increased odds of a late rise rescue (OR (CI) =?2.9 (1.0, 8.5); late rise vs. early rise), while increasing MEP was associated with a no rise rescue (OR (CI) =?1.6 (0.9, 2.8); no rise vs. early rise). CONCLUSIONS:The reported associations varied in their direction of effect, some potentially protective, others adverse. This may reflect the complexity with which these potential endocrine disrupting chemicals can be acting, but chance findings are also possible. Given that women continue to be exposed to these compounds (or their precursors), continued research on the effects they may have on pregnancy is warranted.

Dataset Information

Altered blood proteome in girls with high urine concentrations of bisphenol a, genistein, mono-ethyl hexylphthalate and mono-benzyl phthalate.

Publications

Altered blood proteome in girls with high urine concentrations of bisphenol a, genistein, mono-ethyl hexylphthalate and mono-benzyl phthalate.

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