Biomaterial Database

PFOS Modulates Interactive Epigenetic Regulation in First-Trimester Human Trophoblast Cell Line HTR-8/SVneo. 2019

Ravi Sonkar, and Matthew K Kay, and Mahua Choudhury

Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy , Texas A&M Health Science Center , 312 REYN, MS 1114 , College Station , Texas 77843 , United States.

Organic compounds have been linked to adverse pregnancy complications. Perfluorooctanesulfonic acid (PFOS), a man-made fluorosurfactant and global pollutant, has been shown to induce oxidative stress in various cell types. Oxidative stress plays a key role in leading several placental diseases including preeclampsia (PE), gestational diabetes, spontaneous abortion, preterm labor, and intrauterine growth restriction. Recently, epigenetic regulation such as histone modifications, DNA methylation, and microRNAs (miRNAs), are shown to be associated with oxidative stress as well as pregnancy complications such as PE. However, whether PFOS exerts its detrimental effects in the placenta through epigenetics remains to be unveiled. Therefore, we aimed to investigate the effect of PFOS-induced reactive oxygen species (ROS) generation in first trimester human trophoblast cell line (HTR-8/SVneo) and whether epigenetic regulation is involved in this process. When treated with a range of PFOS doses at 24 and 48 h, even at 10 μM, it significantly increased the ROS production and decreased gene and protein expression, respectively, of the DNA methyltransferases DNMT1 (p < 0.001; p < 0.05), DNMT3A (p < 0.001; p < 0.05), and DNMT3B (p < 0.01; p < 0.01) and the sirtuins, for example, SIRT1 (p < 0.001; p < 0.001) and SIRT3 (p < 0.001; p < 0.05), while reducing global DNA methylation (p < 0.01) and increasing protein lysine acetylation (p < 0.001) as compared to vehicle controls. Interestingly, PFOS (10 μM) significantly increased miR29-b (p < 0.01), which has been previously reported to be associated with PE. The observed epigenetic effects were shown to be dependent on the expression of miR-29b, as knockdown of miR-29b significantly alters the gene and protein expression of DNMT1, DNMT3A, DNMT3B, SIRT1, and SIRT3 and ROS production as well as global DNA methylation and protein acetylation. This study provides for the first time a novel insight into PFOS-induced ROS generation via regulation of sets of the interactive epigenetic circuit in the placenta, which may lead to pregnancy complications.

UI	MeSH Term	Description	Entries
D011247	Pregnancy	The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.	Gestation,Pregnancies
D011261	Pregnancy Trimester, First	The beginning third of a human PREGNANCY, from the first day of the last normal menstrual period (MENSTRUATION) through the completion of 14 weeks (98 days) of gestation.	Early Placental Phase,Pregnancy, First Trimester,Trimester, First,Early Placental Phases,First Pregnancy Trimester,First Pregnancy Trimesters,First Trimester,First Trimester Pregnancies,First Trimester Pregnancy,First Trimesters,Phase, Early Placental,Phases, Early Placental,Placental Phase, Early,Placental Phases, Early,Pregnancies, First Trimester,Pregnancy Trimesters, First,Trimesters, First
D002470	Cell Survival	The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.	Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D005260	Female		Females
D005466	Fluorocarbons	Liquid perfluorinated carbon compounds which may or may not contain a hetero atom such as nitrogen, oxygen or sulfur, but do not contain another halogen or hydrogen atom. This concept includes fluorocarbon emulsions, and fluorocarbon blood substitutes. Perfluorinated and related polyfluorinated chemicals are referred to as PFAS and are defined as chemicals with at least two adjacent carbon atoms, where one carbon is fully fluorinated and the other is at least partially fluorinated.	Fluorocarbon,Fluorocarbon Emulsion,Fluorocarbon Emulsions,Fluorotelomer Phosphate Esters,N-Alkyl Perfluoroalkyl Sulfonamido Carboxylates,PFAS Per- and Polyfluoroalkyl Substances,PFC Perfluorinated Chemicals,PFECAs Perfluoropolyether Carboxylic Acids,Per- and Polyfluoroalkyl Substances,Perfluoroalkane Sulfonamides,Perfluoroalkyl Carboxylates,Perfluoroalkyl Ether Carboxylates,Perfluoroalkyl Polyether Carboxylates,Perfluorocarbon,Perfluorocarbons,Perfluoropolyether Carboxylic Acids,Polyfluorocarbons,Fluorinated Telomer Alcohols,Fluoro-Telomer Alcohols,Polyfluorinated Telomer Alcohols,Telomer Fluorocarbons,Acids, Perfluoropolyether Carboxylic,Alcohols, Fluorinated Telomer,Alcohols, Fluoro-Telomer,Alcohols, Polyfluorinated Telomer,Carboxylates, Perfluoroalkyl,Carboxylates, Perfluoroalkyl Ether,Carboxylates, Perfluoroalkyl Polyether,Carboxylic Acids, Perfluoropolyether,Chemicals, PFC Perfluorinated,Emulsion, Fluorocarbon,Emulsions, Fluorocarbon,Esters, Fluorotelomer Phosphate,Ether Carboxylates, Perfluoroalkyl,Fluoro Telomer Alcohols,Fluorocarbons, Telomer,N Alkyl Perfluoroalkyl Sulfonamido Carboxylates,PFAS Per and Polyfluoroalkyl Substances,Per and Polyfluoroalkyl Substances,Perfluorinated Chemicals, PFC,Phosphate Esters, Fluorotelomer,Polyether Carboxylates, Perfluoroalkyl,Sulfonamides, Perfluoroalkane,Telomer Alcohols, Fluorinated,Telomer Alcohols, Polyfluorinated
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014327	Trophoblasts	Cells lining the outside of the BLASTOCYST. After binding to the ENDOMETRIUM, trophoblasts develop into two distinct layers, an inner layer of mononuclear cytotrophoblasts and an outer layer of continuous multinuclear cytoplasm, the syncytiotrophoblasts, which form the early fetal-maternal interface (PLACENTA).	Cytotrophoblasts,Syncytiotrophoblasts,Trophoblast,Cytotrophoblast,Syncytiotrophoblast
D017382	Reactive Oxygen Species	Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of SIGNAL TRANSDUCTION and GENE EXPRESSION, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.	Active Oxygen Species,Oxygen Radical,Oxygen Radicals,Pro-Oxidant,Reactive Oxygen Intermediates,Active Oxygen,Oxygen Species, Reactive,Pro-Oxidants,Oxygen, Active,Pro Oxidant,Pro Oxidants,Radical, Oxygen
D017738	Alkanesulfonic Acids	Sulfonic acid derivatives that are substituted with an aliphatic hydrocarbon group.	Acids, Alkanesulfonic