An assessment of serum-dependent impacts on intracellular accumulation and genomic response of per- and polyfluoroalkyl substances in a placental trophoblast model.
An assessment of serum-dependent impacts on intracellular accumulation and genomic response of per- and polyfluoroalkyl substances in a placental trophoblast model.
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DOI：
10.1002/tox.23004
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发表时间：
2020-12
影响因子：
4.5
通讯作者：
C Fry R
中科院分区：
文献类型：
--
作者：
Bangma J;Szilagyi J;Blake BE;Plazas C;Kepper S;Fenton SE;C Fry R
全氟烷基和多氟烷基物质（PFAS）是在人类胎盘和脐带血中检测到的一系列环境污染物。PFAS诱导不良妊娠结局和对胎盘影响的机制尚未完全了解。我们研究了全氟辛烷磺酸（PFOS）、全氟辛酸（PFOA）和一种称为六氟环氧丙烷二聚酸（HFPO-DA，商品名GenX）的替代PFAS对体外胎盘滋养层的影响。首先，我们评估了可能影响数据质量的因素，包括常用细胞培养试剂中PFAS的定量。其次，我们研究了补充培养基血清在人滋养层细胞（JEG 3）细胞系中PFAS细胞内积累的作用。最后，我们评估了PFAS对JEG 3细胞中参与胎盘正常功能的96个基因的mRNA表达的影响。分析结果显示，在基线时，无血清培养基（SFM）不含可检测的PFAS。胎牛血清补充培养基（SSM）含有PFNA、PFUdA、PFTrDA和6：2 FTS，但在细胞内部未检测到这些PFAS。24小时治疗后的细胞内积累显着较高时，培养在SFM相比，SSM的全氟辛烷磺酸和全氟辛酸，但不HFPO-DA。最后，PFAS曝光与适度的基因表达变化的途径至关重要的胎盘功能，包括活力，合胞，炎症，运输，和入侵/间质转化。在PFAS相关的变化中，最强大的是在BAD和BAX中观察到的变化，这是一种与肥胖相关的基因。这些结果表明PFAS和体外培养条件之间存在复杂的关系，PFAS改变了滋养层参与胎盘形成所必需的关键基因。
Per- and polyfluoroalkyl substances (PFAS) are a family of environmental contaminants that have been detected in human placenta and cord blood. The mechanisms driving PFAS-induced adverse pregnancy outcomes and effects on the placenta are not well understood. We investigated the impact of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and a replacement PFAS known as hexafluoropropylene oxide dimer acid (HFPO-DA, tradename GenX) on placental trophoblasts in vitro. First, we assessed factors that can influence data quality including quantification of PFAS in common cell culture reagents. Second, we investigated the role of supplemental media serum in intracellular accumulation of PFAS in a human trophoblast (JEG3) cell line. Finally, we evaluated the impact of PFAS on mRNA expression of 96 genes involved in proper placental function in JEG3 cells. Analytical results revealed that, at baseline, serum-free media (SFM) contained no detectable PFAS. Fetal bovine serum-supplemented media (SSM) contained PFNA, PFUdA, PFTrDA, and 6:2 FTS, but these PFAS were not detected internally in cells. Intracellular accumulation following 24 hr treatments was significantly higher when cultured in SFM compared to SSM for PFOS and PFOA, but not HFPO-DA. Finally, PFAS exposure was associated with modest gene expression changes in pathways vital to placental function, including viability, syncytialization, inflammation, transport, and invasion/mesenchymal transition. Among the most robust PFAS-associated changes were those observed in BAD and BAX, apoptosis-related genes. These results suggest a complex relationship between PFAS and culture conditions in vitro, and that PFAS alter key genes necessary for trophoblast involvement in placentation.
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DOI：
10.1016/j.fct.2016.06.023
发表时间：
2016-12
期刊：
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
影响因子：
--
作者：
Brooks SA;Martin E;Smeester L;Grace MR;Boggess K;Fry RC
通讯作者：
Fry RC
DOI：
10.1016/j.reprotox.2009.02.012
发表时间：
2009-06
期刊：
Reproductive toxicology (Elmsford, N.Y.)
影响因子：
--
作者：
Fenton SE;Reiner JL;Nakayama SF;Delinsky AD;Stanko JP;Hines EP;White SS;Lindstrom AB;Strynar MJ;Petropoulou SE
通讯作者：
Petropoulou SE
影响因子：
11.4
作者：
Escher, BI;Hermens, JLM
通讯作者：
Hermens, JLM
影响因子：
5
作者：
Ashley-Martin J;Dodds L;Arbuckle TE;Bouchard MF;Fisher M;Morriset AS;Monnier P;Shapiro GD;Ettinger AS;Dallaire R;Taback S;Fraser W;Platt RW
通讯作者：
Platt RW
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y