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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.
Show more [+] Less [-]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.
Show more [+] Less [-]LncRNA MEG3 alleviates PFOS induced placental cell growth inhibition through its derived miR-770 targeting PTX3
2022
Li, Jing | Quan, Xiaojie | Lei, Saifei | Chen, Gang | Hong, Jiawei | Huang, Zhenyao | Wang, Qi | Song, Weiyi | Yang, Xinxin
Perfluorooctane sulfonic acid (PFOS) is a persistent environmental pollutant. Exposure to PFOS has been associated with abnormal fetal development. The long non-coding RNA (lncRNA) has been showed to play a role in fetal growth restriction (FGR), preeclampsia (PE) and other pregnancy complications. Whether the lncRNA contributes to PFOS-induced toxicity in the placenta remains unknown. In this study, we investigated the function of lncRNA MEG3 and its derived miR-770 in PFOS-induced placental toxicity. Pregnant mice received gavage administration of different concentrations of PFOS (0.5, 2.5, and 12.5 mg/kg/day) from GD0 to GD17, and HTR-8/SVneo cells were treated with PFOS in the concentrations of 0, 10⁻¹, 1, 10 μM. We found that expression levels of miR-770 and its host gene MEG3 were reduced in mice placentas and HTR-8/SVneo cells with exposure of PFOS. A significant hypermethylation was observed at MEG3 promoter in placentas of mice gestational-treated with PFOS. We also confirmed that MEG3 and miR-770 overexpression alleviated the cell growth inhibition induced by PFOS. Furthermore, PTX3 (Pentraxin 3) was identified as the direct target of miR-770 and it was enhanced after PFOS exposure. In summary, our results suggested that MEG3 alleviate PFOS-induced placental cell inhibition through MEG3/miR-770/PTX3 axis.
Show more [+] Less [-]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.
Show more [+] Less [-]Human exposure to PBDEs in e-waste areas: A review
2020
Polybrominated biphenyl ethers (PBDEs) are commonly added to electronic products for flame-retardation effects, and are attracting more and more attentions due to their potential toxicity, durability and bioaccumulation. This study conducts a sysmtematic review to understand the human exposure to PBDEs from e-waste recycling, especially exploring the exposure pathways and human burden of PBDEs as well as investigating the temporal trend of PBDEs exposure worldwide. The results show that the particular foods (contaminated fish, poultry, meat and breast milk) ingestion, indoor dust ingestion and indoor air inhalation may be key factors leading to human health risks of PBDEs exposure in e-waste recycling regions. Residents and some vulnerable groups (occupational workers and children) in e-waste recycling areas may face higher exposure levels and health risks. PBDE exposure is closely related to exposure level, exposure duration, e-waste recycling methods, and dietary customs. High levels of PBDEs are found in human tissues (breast milk, hair, blood (serum), placenta and other tissues) in e-waste areas, at far higher levels than in other areas. Existing data indicate that PBDE exposure levels do not present any apparent downward trend, and will possibly cause serious human diseases. More epidemiological studies are still needed to provide a solid basis for health risk assessment.
Show more [+] Less [-]Maternal transfer of phenol derivatives in the Baltic grey seal Halichoerus grypus grypus
2018
Nehring, Iga | Falkowska, Lucyna | Staniszewska, Marta | Pawliczka, Iwona | Bodziach, Karina
Studies of circulating levels in difference sex and age classes, and maternal transfer of bisphenol A, 4-tert-octylphenol and 4- nonylphenol in the Baltic grey seal were performed from 2014-2017. Blood was collected from long-term captive adult males, pregnant females and pups. Milk was collected from nursing females. The aim of this study was not only to determine the concentrations of phenol derivatives, i.e. bisphenol A (BPA), 4-tert-octylphenol (OP) and 4-nonylphenol (NP), but also to try to evaluate the transfer of these compounds to the next generation in the final stage of foetal life and in the first few weeks of life in juvenile marine mammals. The measurements were carried out using high performance liquid chromatography. The obtained data show that all phenol derivatives are present in the blood of males, females and pups (range <0.07–101 ng·cm⁻³) and in female milk (range <0.1–406.3 ng·cm⁻³). The main source of phenol derivatives in organisms is food exposure. Gender, age, or number of births were not observed to have a significant effect on changes in phenol derivative levels in seal blood within the breeding group. In the prenatal stage of life, a small amount of BPA and alkylphenols was passed on to the offspring through the placenta. In the blood of the offspring the concentration of these compounds exceeded the concentration in the mother's blood 1.5-fold. During nursing, females detoxified their systems. Level of phenol derivatives in the pups blood increased linearly with its increasing concentrations in the mother's milk. On the other hand, the seafood diet which started after the physiological fasting stage of the pup, stabilised the levels of phenol derivatives below 10 ng ∙ cm⁻³.
Show more [+] Less [-]Mercury, selenium and stable isotopes in four small cetaceans from the Southeastern Brazilian coast: Influence of feeding strategy
2016
Baptista, Gilberto | Kehrig, Helena A. | Di Beneditto, Ana Paula M. | Hauser-Davis, Rachel A. | Almeida, Marcelo G. | Rezende, Carlos E. | Siciliano, Salvatore | de Moura, Jailson F. | Moreira, Isabel
Dolphins are good bioindicators of the contamination status of marine ecosystems, since their dietary and habitat plasticity in both coastal and offshore ecotypes provide information on the trace elements levels originated from natural and anthropogenic sources. In this context, this study aimed to investigate provides mercury (Hg), selenium (Se) levels, trophic ecology and feeding environments of four small cetaceans (Tursiops truncatus, Steno bredanensis, Sotalia guianensis and Pontoporia blainvillei) inhabiting the central-northern coast of Rio de Janeiro State, southeastern Brazil. For the latter, δ15N and δ13C stable isotopes were used as indicators in this regard. Stable isotope values indicate that the four studied species have distinctive foraging habitats, coastal and least coastal, and occupy different trophic positions. The significant relationship found between muscle Hg and δ15N suggests that individual foraging preference remains relatively constant for the studied dolphin species over extended periods. The individual prey size and species are probably responsible for the differences found in Hg and Se concentrations in muscle tissue among all dolphin species. The vulnerable small coastal cetacean, P. blainvillei, which feeds on small teleost fish and squid, presented the lowest muscular Hg concentrations (less than 3.5 μg g−1 dry wt.). Meanwhile, S. bredanensis is more likely to uptake large amounts of trace elements among the four dolphin species, due to its feeding habits mainly being large offshore fish that accumulate high amounts of trace elements in organs and tissues. Differences found between Hg concentrations in fetus-mother pairs were much higher in S. guianensis than in P. blainvillei, suggesting that maternal contribution of Hg via placenta was more significant for the former.
Show more [+] Less [-]Mercury concentrations in human placenta, umbilical cord, cord blood and amniotic fluid and their relations with body parameters of newborns
2013
Kozikowska, Iwona | Binkowski, Łukasz J. | Szczepańska, Katarzyna | Sławska, Helena | Miszczuk, Katarzyna | Śliwińska, Magdalena | Łaciak, Tomasz | Stawarz, Robert
Studies were conducted on samples taken from giving birth women (n = 40) living in Poland, representing three age groups: 19–25, 26–30 and 31–38 years old. Mercury concentrations were measured with CV-AAS in placenta, umbilical cord, cord blood and amniotic fluid.The placentas weight did not exceed the 750 g value and was heavier than 310 g. Mean values of Hg concentrations in blood, placenta and umbilical cord were similar (c.a. 9 μg/g). High levels of mercury were noted in cord blood which in 75% of all observations exceeded (up to 17 μg/L) the safe dose set by US EPA (5.8 μg/L). No statistically significant differences in medium level of Hg in all the studied tissues among age groups of women were observed. Positive correlations between Hg concentrations in placenta and umbilical cord and cord blood were revealed as well as some negative ones between mercury concentrations and pregnancy parameters.
Show more [+] Less [-]Levels of prenatal mercury exposure and their relationships to neonatal anthropometry in Wujiang City, China
2013
Guo, Bao-Qiang | Cai, Shi-Zhong | Guo, Jun-Liang | Xu, Jian | Wu, Wei | Li, Hui | Zhou, Xin | Kim, Dae-Seon | Yan, Chong-Huai | Lü, Hong-Dao
We determined the levels of prenatal Hg exposure in Wujiang City, located in the southeast of Taihu Lake in China's Jiangsu Province, and analyze the relationship between prenatal exposure to Hg and neonatal anthropometry, including birth weight, body length, and head circumference. From June 2009 to July 2010, a total of 213 mother-infant pairs were enrolled. The geometric means of Hg levels in maternal hair, fetal hair, placentas, and cord blood were 496.76 μg/kg, 233.94 μg/kg, 3.58 μg/kg, and 1.54 μg/L, respectively. The Hg levels detected in our study were significantly lower than those reported by previous studies. In addition, no significant correlations were found between Hg levels in maternal hair, fetal hair, placenta, or cord blood and neonatal anthropometrics. Together, our findings may be important for understanding the effects of prenatal exposure to Hg on newborns' development and have implications concerning the recommended dose for Hg.
Show more [+] Less [-]Accumulation and maternal transfer of polychlorinated biphenyls in Steller Sea Lions (Eumetopias jubatus) from Prince William Sound and the Bering Sea, Alaska
2011
Wang, Jun | Hülck, Kathrin | Hong, Su-Myeong | Atkinson, Shannon | Li, Qing X.
The western stock of the Steller sea lion (Eumetopias jubatus) in the northern Pacific Ocean has declined by approximately 80% over the past 30 years. This led to the listing of this sea lion population as an endangered species in 1997. Chemical pollution is a one of several contributing causes. In the present study, 145 individual PCBs were determined in tissues of male sea lions from Tatitlek (Prince William Sound) and St. Paul Island (Bering Sea), and placentae from the Aleutian Islands. PCBs 90/101, 118, and 153 were abundant in all the samples. The mean toxic equivalents (TEQ) were 2.6, 4.7 and 7.4pg/g lw in the kidney, liver, and blubber samples, respectively. The mean TEQ in placentae was 8pg/g lw. Total PCBs concentrations (2.6–7.9μg/g lw) in livers of some males were within a range known to cause physiological effects. Further suggesting the possibility of adverse effects on this stock.
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