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Pregnancy exposure to synthetic phenols and placental DNA methylation -An epigenome-wide association study in male infants from the EDEN cohort ☆
2021
Jedynak, Paulina | Tost, Jörg | Calafat, Antonia, M | Bourova-Flin, Ekaterina | Busato, Florence | Forhan, Anne | Heude, Barbara | Jakobi, Milan | Rousseaux, Sophie | Schwartz, Joel | Slama, Rémy | Vaiman, Daniel | Philippat, Claire | Lepeule, Johanna | Université Grenoble Alpes (UGA) | Centre for Research in Epidemiology and Statistics | Centre de Recherche Épidémiologie et Statistiques (CRESS (U1153 / UMR_A 1125)) ; Conservatoire National des Arts et Métiers [CNAM] (CNAM) ; HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
International audience | In utero exposure to environmental chemicals, such as synthetic phenols, may alter DNA methylation in different tissues, including placenta - a critical organ for fetal development. We studied associations between prenatal urinary biomarker concentrations of synthetic phenols and placental DNA methylation. Our study involved 202 mother-son pairs from the French EDEN cohort. Nine phenols were measured in spot urine samples collected between 22 and 29 gestational weeks. We performed DNA methylation analysis of the fetal side of placental tissues using the IlluminaHM450 BeadChips. We evaluated methylation changes of individual CpGs in an adjusted epigenome-wide association study (EWAS) and identified differentially methylated regions (DMRs). We performed mediation analysis to test whether placental tissue heterogeneity mediated the association between urinary phenol concentrations and DNA methylation. We identified 46 significant DMRs (>= 5 CpGs) associated with triclosan (37 DMRs), 2,4-dichlorophenol (3), benzophenone-3 (3), methyl- (2) and propylparaben (1). All but 2 DMRs were positively associated with phenol concentrations. Out of the 46 identified DMRs, 7 (6 for triclosan) encompassed imprinted genes (APC, FOXG1, GNAS, GNASAS, MIR886, PEG10, SGCE), which represented a significant enrichment. Other identified DMRs encompassed genes encoding proteins responsible for cell signaling, transmembrane transport, cell adhesion, inflammatory, apoptotic and immunological response, genes encoding transcription factors, histones, tumor suppressors, genes involved in tumorigenesis and several cancer risk biomarkers. Mediation analysis suggested that placental cell heterogeneity may partly explain these associations. This is the first study describing the genome-wide modifications of placental DNA methylation associated with pregnancy exposure to synthetic phenols or their precursors. Our results suggest that cell heterogeneity might mediate the effects of triclosan exposure on placental DNA methylation. Additionally, the enrichment of imprinted genes within the DMRs suggests mechanisms by which certain exposures, mainly to triclosan, could affect fetal development.
Показать больше [+] Меньше [-]Pregnancy exposure to synthetic phenols and placental DNA methylation -An epigenome-wide association study in male infants from the EDEN cohort ☆
2021
Jedynak, Paulina | Tost, Jörg | Calafat, Antonia, M | Bourova-Flin, Ekaterina | Busato, Florence | Forhan, Anne | Heude, Barbara | Jakobi, Milan | Rousseaux, Sophie | Schwartz, Joel | Slama, Rémy | Vaiman, Daniel | Philippat, Claire | Lepeule, Johanna | Université Grenoble Alpes (UGA) | Centre for Research in Epidemiology and Statistics | Centre de Recherche Épidémiologie et Statistiques (CRESS (U1153 / UMR_A 1125)) ; Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
International audience | In utero exposure to environmental chemicals, such as synthetic phenols, may alter DNA methylation in different tissues, including placenta - a critical organ for fetal development. We studied associations between prenatal urinary biomarker concentrations of synthetic phenols and placental DNA methylation. Our study involved 202 mother-son pairs from the French EDEN cohort. Nine phenols were measured in spot urine samples collected between 22 and 29 gestational weeks. We performed DNA methylation analysis of the fetal side of placental tissues using the IlluminaHM450 BeadChips. We evaluated methylation changes of individual CpGs in an adjusted epigenome-wide association study (EWAS) and identified differentially methylated regions (DMRs). We performed mediation analysis to test whether placental tissue heterogeneity mediated the association between urinary phenol concentrations and DNA methylation. We identified 46 significant DMRs (>= 5 CpGs) associated with triclosan (37 DMRs), 2,4-dichlorophenol (3), benzophenone-3 (3), methyl- (2) and propylparaben (1). All but 2 DMRs were positively associated with phenol concentrations. Out of the 46 identified DMRs, 7 (6 for triclosan) encompassed imprinted genes (APC, FOXG1, GNAS, GNASAS, MIR886, PEG10, SGCE), which represented a significant enrichment. Other identified DMRs encompassed genes encoding proteins responsible for cell signaling, transmembrane transport, cell adhesion, inflammatory, apoptotic and immunological response, genes encoding transcription factors, histones, tumor suppressors, genes involved in tumorigenesis and several cancer risk biomarkers. Mediation analysis suggested that placental cell heterogeneity may partly explain these associations. This is the first study describing the genome-wide modifications of placental DNA methylation associated with pregnancy exposure to synthetic phenols or their precursors. Our results suggest that cell heterogeneity might mediate the effects of triclosan exposure on placental DNA methylation. Additionally, the enrichment of imprinted genes within the DMRs suggests mechanisms by which certain exposures, mainly to triclosan, could affect fetal development.
Показать больше [+] Меньше [-]Mechanisms of transplacental transport and barrier of polybrominated diphenyl ethers: A comprehensive human, Sprague-Dawley rat, BeWo cell and molecular docking study
2021
Yu, Yingxin | Li, Xiaojing | Hu, Junjie | Jiang, Zi’an | Zhang, Xiaolan | Li, Guiying | Ma, Shengtao | Lei, Bingli | Fang, Xiangming | Fan, Ruifang | An, Taicheng
Although studies have reported that polybrominated diphenyl ethers (PBDEs) can transfer from mothers to fetuses, the underlying transplacental transport and barrier mechanisms are still unclear. Therefore, we conducted a series of comprehensive experiments in humans, Sprague-Dawley rats, and a BeWo cell monolayer model, as well as a molecular docking study. PBDEs in mothers can transfer to fetuses with a ratio of approximately 0.46, suggesting that the placenta could not efficiently acts as a barrier to PBDE transplacental transport. Similar results were observed in pregnant rats, although varying times were required for different congeners to reach a steady-state in fetuses. The transport ratios at pregnancy day 14 in rats were generally higher than those at pregnancy day 18, which demonstrated that the barrier capacity of immature placentas was lower than that of mature placentas. None concentration-dependent transplacental transport was observed in BeWo cells with efflux ratios of 1.73–2.32, which suggested passive diffusion mechanisms govern the influx of PBDEs through placenta. The accumulated ratios of PBDEs and the inhibitor assay indicated that the effluent channel of P-glycoprotein was partially inhibited by PBDEs. Using molecular docking studies, three pocket sites were identified for different congeners in P-glycoprotein, which demonstrated that the inhibition of P-glycoprotein efflux pump through the pocket sites.
Показать больше [+] Меньше [-]Association of maternal exposure to bisphenol A with her β-hCG level and neonatal anthropometric measures
2021
Amin, Mohammad Mehdi | Ghasemi, Zahra | Khoshhali, Mehri | Taheri, Ensiyeh | Dehdashti, Bahare | Fatehizadeh, Ali | Rafiei, Nasim | Kelishadi, Roya
Bisphenol A (BPA) is one of the organic compounds that might interfere with estrogenic receptors, which would make difficulties in pregnancy hormones and fetal growth. Human chorionic gonadotropin (β-hCG) is one of the important pregnancy hormones that might be affected by environmental pollutants. The aim of this study is to investigate the probable impacts of maternal exposure to BPA on anthropometric measures of newborns. This cross-sectional study was conducted in 2019–2020 in Isfahan, Iran. During the first trimester of pregnancy, we measured the urinary BPA concentration and serum β-hCG level of 120 pregnant women, who were randomly selected from participants of a birth cohort. BPA concentration was measured using gas chromatography–mass spectrometry (GC-MS). Serum blood sample was derived and used for β-hCG analysis. Anthropometric measurement of neonates was conducted at the time of birth. BPA and β-hCG level were grouped by quartiles, and their associations with birth weight, height, and head circumference were tested using multiple linear regression model. The adjustment was done for urine creatinine, gender, and gestational age, as well as maternal age, body mass index, and education level. Data of 119 pairs of mothers and infants were available for the present study. The mean (SD) age of mothers was 29.19 (5.75) years; 56.3% of newborns were boys. Geometric mean of urinary BPA and β-hCG concentrations were 0.36 ng/g crea. (creatinine) and 17736 mIU/ml, respectively. Across the BPA tertiles, the differences in mean values were not significant for none of the anthropometric measurements and gestational age (GA). Furthermore, no significant association existed between unadjusted and adjusted tertiles of BPA and β-hCG with abovementioned birth outcomes. It seems that the non-significant association found in this study is because of low levels of urinary BPA levels than in other studies; the adverse effects on infants might be related to high concentration of BPA passed from placenta. Future longitudinal studies with large sample size are necessary to document the adverse health effects of maternal exposure to endocrine disruptor chemicals including BPA.
Показать больше [+] Меньше [-]Serum level of lead and cadmium is linked to facial cosmetics use among Iranian young women
2021
Parizi, Maryam Ghaseminasab | Sedaghat, Zahra | Mazloomi, Mohammad | Fararouei, Mohammad
Cosmetics are applied widely by women and men for different proposes mainly beauty and skin care. However, the biologically active substances which are used in these products and their health effects are not fully known. The aims of this study were, first, to estimate the prevalence of cosmetics use, and second, to examine if any association exists between cosmetic use and serum levels of lead and cadmium (two heavy metals with major health effects) among young women. This is a cross-sectional study conducted on 65 female students during the first semester of 2017 academic year. Study sample was selected randomly using phone numbers. About 70% of the study participants started using cosmetics under age 20 years (about 14% under 15), and 50% were using the products on a daily base. After adjusting for possible confounders, significant associations were found between the participants age (B = − 0.0008, CI = − 0.001 to − 4.71, P = 0.03) and duration of using cosmetics (B = 0.0006, CI = 0.0001 to 0.115, P = 0.01) with the level of cadmium in their serum samples. Duration of using cosmetics (B = 0.008, CI 0.001 to 0.01, P = 0.01) was the only variable which was significantly associated with serum level of lead in the participants. According to the results of the present study, most Iranian girls start using cosmetics at a very young age making them more vulnerable to the potential hazards of the ingredients of cosmetic products including heavy metals and preservatives. The association between duration of using cosmetics and serum level of lead and cadmium may cause serious health problems for women at young ages and their fetus or children via placenta and breast milk. The big market of cosmetics in many countries especially Middle East is highly important.
Показать больше [+] Меньше [-]Analysis of essential and non-essential trace elements in the organs of a mother–fetus pair of spotted seals (Phoca largha) from the Sea of Japan
2021
Simokon, Mikhail V. | Trukhin, Alexey M.
Concentrations of 22 essential and non-essential trace elements (Be, Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Mo, Ag, Cd, Sb, Ba, Tl, Pb, Th, U, and Hg) were measured in the organs of a mother–fetus pair (at the last trimester of pregnancy) of spotted seals from the Sea of Japan. The concentrations of eleven elements are reported for the first time. Eight organs of the pair were examined: lungs, heart, liver, kidneys, intestines, spleen, muscles, and bones. All trace elements detected in the organs of the mother were found also in the organs of the fetus at various concentrations. Placenta is not an effective barrier to prevent non-essential elements from getting into the fetus, but can control entry of some of them, e.g., aluminum, cadmium, and mercury. In most organs of the fetus, the concentrations of toxic trace elements (beryllium, antimony, thorium, and uranium) were noticeably higher than in the same organs of the mother, which indicates that during pregnancy female removes excess of non-essential trace elements by transferring them to the fetal body through the placental barrier.
Показать больше [+] Меньше [-]Association between placenta concentrations polybrominated and polychlorinated biphenyls and gestational diabetes mellitus: a case-control study in northwestern Spain
2021
Alvarez-Silvares, Esther | Fernández-Cruz, Tania | Domínguez-Vigo, Paula | Rubio-Cid, Paula | Seoane-Pillado, Teresa | Martínez-Carballo, Elena
Exposure to persistent organic pollutants begins in uterine life. The study was conducted to evaluate associations between gestational diabetes mellitus and the presence of persistent organic pollutants in placenta samples. They were derived from a birth cohort study in Ourense (NW Spain). Selective pressurized liquid extraction methodologies were used to determine targeted persistent organic pollutants in placenta samples. Cleanup of extracts was performed by solid-phase extraction using EZ-POP cartridges and detection by gas chromatography coupled to tandem mass spectrometry. Statistical calculations were performed by comparing the values obtained in the case and control groups. Statistical significance was considered as p < 0.050. Results: The concentrations of several congeners of polybrominated diphenyl ethers (PBDE) and polychlorinated biphenyls (PCB) presented lower levels in the placentas of expectant mothers with gestational diabetes mellitus when comparing them to the control cohort. This difference was statistically significant. It was revealed that this association was independent of obesity, age, parity, amenorrhoea at birth, or a family history of diabetes mellitus. To the best of our knowledge, this paper reported an inverse relationship between PBDE and PCB levels in placenta and gestational diabetes mellitus for the first time. We believe this may open a door to future studies in this field.
Показать больше [+] Меньше [-]Increased expression of apoptotic markers in human full-term placenta after exposure to elevated environmental cadmium levels during pregnancy
2021
Phuapittayalert, Laorrat | Tanasrivaroottanun, Nathamon | Hipkaeo, Wiphawi | Supanpaiboon, Wisa | Sakulsak, Natthiya
Cadmium (Cd), a toxic heavy metal, produces various forms of environmental contaminations and health problems in human. In this study, we aimed to examine the localization of several apoptotic markers in human placentas from pregnant women who were environmentally exposed to Cd. Twelve pregnant women participated in this analysis and they were divided into 2 groups according to their living areas: high-Cd (H-Cd) and low-Cd (L-Cd) groups. After delivery, the placentas were immediately harvested, and the placental width, length, and weight were measured. The placental Cd concentration was determined by using ICP-MS. The expression of three apoptotic markers, cleaved caspase-3, cleaved lamin A/C, and TUNEL, was examined in immunohistochemistry. In results, the placental Cd concentration in the H-Cd group was higher than that in the L-Cd group. In contrast, a significant decrease in the BW (birth weight):PW (placenta weight) ratio representing the placental nutrient transport function was found in the H-Cd group, and an inverse correlation between placental Cd concentration and BW:PW ratio was demonstrated. Additionally, significant elevations in the expression of cleaved caspase-3, cleaved lamin A/C proteins, and TUNEL were shown in the H-Cd placenta. Moreover, positive correlations were found between the placental Cd concentration and the expression of cleaved caspase-3 and TUNEL. Collectively, our findings suggest that the exposure of pregnant women to environmental Cd might induce Cd to be transferred to the body and then accumulated in the placenta, resulting in disturbance of the placental function and eventual apoptosis.
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