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孕期接触邻苯二甲酸盐和个人护理产品会改变双胎妊娠胎盘细胞外微小RNA谱。

Maternal Phthalate and Personal Care Products Exposure Alters Extracellular Placental miRNA Profile in Twin Pregnancies.

作者信息

Zhong Jia, Baccarelli Andrea A, Mansur Abdallah, Adir Michal, Nahum Ravit, Hauser Russ, Bollati Valentina, Racowsky Catherine, Machtinger Ronit

机构信息

1 Environmental Precision Biosciences Laboratory, Columbia University, Mailman School of Public Health, New York, NY, USA.

2 Department of Obstetrics and Gynecology, Sheba Medical Center, Ramat-Gan and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

出版信息

Reprod Sci. 2019 Feb;26(2):289-294. doi: 10.1177/1933719118770550. Epub 2018 Apr 24.

Abstract

Prenatal exposure to endocrine-disrupting chemicals (EDCs) exerts both short- and long-term adverse effects on the developing fetus. However, the mechanisms underlying these effects have yet to be uncovered. Maternal-fetal signaling is mediated in part by signaling molecules (eg, microRNAs [miRNAs]) contained in extracellular vesicles (EVs) that are released by the placenta into the maternal circulation. We investigated whether maternal exposure to the EDCs phthalates and personal care products alters the miRNA profile of placental-derived EVs circulating in maternal blood. Blood and urine samples from pregnant women with uncomplicated term dichorionic, diamniotic twin pregnancies were analyzed as part of a larger study investigating correlations between exposure of phthalate and personal care products and epigenetic alterations in twin pregnancies. We explored correlations between maternal urinary levels of 13 phthalate and 12 personal care products metabolites and the miRNA profile of placental EVs (EV-miRNAs) circulating in maternal blood. The expression of miR-518e was highest among women with high urinary levels of monobenzyl phthalate and methyl paraben. miR-373-3p was the least expressed in women exposed to high levels of methyl paraben, and miR-543 was significantly downregulated in women exposed to high levels of paraben metabolites, dichlorophenol metabolites, and triclosan. In conclusion, this pilot study reveals that prenatal exposure to EDCs is associated with altered profile of circulating placenta-derived EV-miRNAs. Further studies are needed to generalize these results to singleton pregnancies and to assess whether these alterations are associated with pregnancy complications.

摘要

产前暴露于内分泌干扰化学物质(EDCs)会对发育中的胎儿产生短期和长期的不良影响。然而,这些影响背后的机制尚未被揭示。母胎信号传导部分由细胞外囊泡(EVs)中包含的信号分子(如微小RNA [miRNAs])介导,这些囊泡由胎盘释放到母体循环中。我们研究了母体暴露于EDCs邻苯二甲酸盐和个人护理产品是否会改变母体血液中循环的胎盘来源EVs的miRNA谱。作为一项更大规模研究的一部分,对患有无并发症足月双绒毛膜、双羊膜囊双胎妊娠的孕妇的血液和尿液样本进行了分析,该研究调查了邻苯二甲酸盐和个人护理产品暴露与双胎妊娠表观遗传改变之间的相关性。我们探讨了母体尿液中13种邻苯二甲酸盐和12种个人护理产品代谢物水平与母体血液中循环的胎盘EVs(EV-miRNAs)的miRNA谱之间的相关性。在尿中邻苯二甲酸单苄酯和对羟基苯甲酸甲酯水平高的女性中,miR-518e的表达最高。miR-373-3p在暴露于高水平对羟基苯甲酸甲酯 的女性中表达最少,而miR-543在暴露于高水平对羟基苯甲酸酯代谢物、二氯苯酚代谢物和三氯生的女性中显著下调。总之,这项初步研究表明,产前暴露于EDCs与循环胎盘来源的EV-miRNAs谱的改变有关。需要进一步的研究将这些结果推广到单胎妊娠,并评估这些改变是否与妊娠并发症有关。

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Placental outcomes of phthalate exposure.邻苯二甲酸酯暴露的胎盘结局。
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