DOCSLIB.ORG

Per- and Polyfluoroalkyl Substances Differentially Inhibit Placental Trophoblast Migration and Invasion in Vitro John T

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Per- and Polyfluoroalkyl Substances Differentially Inhibit Placental Trophoblast Migration and Invasion in Vitro John T TOXICOLOGICAL SCIENCES, 2020, 1–10 doi: 10.1093/toxsci/kfaa043 Downloaded from https://academic.oup.com/toxsci/advance-article-abstract/doi/10.1093/toxsci/kfaa043/5812793 by University of North Carolina at Chapel Hill user on 19 May 2020 Advance Access Publication Date: March 27, 2020 Research Article Per- and Polyfluoroalkyl Substances Differentially Inhibit Placental Trophoblast Migration and Invasion In Vitro John T. Szilagyi ,*,† Anastasia N. Freedman,* Stewart L. Kepper,* Arjun M. Keshava,* Jackie T. Bangma,*,‡ and Rebecca C. Fry*,†,‡,1 *Department of Environmental Sciences and Engineering, Gillings School of Global Public Health; †Curriculum in Toxicology; and ‡Institute for Environmental Health Solutions, University of North Carolina, Chapel Hill, North Carolina 27516 1To whom correspondence should be addressed at Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, 135 Dauer Drive, CB 7431, Chapel Hill, NC 27516. Fax: (919) 843-9047. E-mail: [email protected]. ABSTRACT Per- and polyfluoroalkyl substances (PFAS) are used as industrial surfactants and chemical coatings for household goods such as Teflon. Despite regulatory efforts to phase out legacy PFAS, they remain detectable in drinking water throughout the United States. This is due to the stability of legacy PFAS and the continued use of replacement compounds. In humans, PFAS have been detected in placenta and cord blood and are associated with low birth weight and preeclampsia risk. Preeclampsia is a leading cause of maternal mortality and is driven by insufficient endometrial trophoblast invasion, resulting in poor placental blood flow. PFAS alter invasion of other cell types, but their impact on trophoblasts is not understood. We therefore assessed the effects of PFAS on trophoblast migration, invasion, and gene expression in vitro. Trophoblast migration and invasion were assessed using a modified scratch assay in the absence or presence of Matrigel, respectively. Treatment with perfluorooctanoic sulfate (PFOS), perfluorooctanoic acid (PFOA), and GenX (1000 ng/ml) each decreased trophoblast migration over 24 h. However, only GenX (1000 ng/ml) significantly inhibited trophoblast invasion. Treatment with PFOS, PFOA, and GenX also decreased trophoblast expression of chemokines (eg, CCL2), chemokine receptors (eg, CCR4), and inflammatory enzymes (eg, ALOX15) involved in migration. Inhibition of chemokine receptors with pertussis toxin (10 ng/ml), a G-protein inhibitor, inhibited trophoblast migration similar to the PFAS. Taken together, PFAS decrease trophoblast migration, invasion, and inflammatory signaling. By understanding the mechanisms involved, it may be possible to identify the biological and exposure factors that contribute to preeclampsia. Key words: PFAS; placenta; trophoblast; preeclampsia; inflammation. Per- and polyfluoroalkyl substances (PFAS) are used as indus- sulfate (PFOS), their stability and the introduction of replace- trial surfactants and chemical coatings for common household ment compounds, such as hexafluoropropylene oxide dimer goods such as Teflon and scotch guard (Renner, 2006; Sajid and acid (ammonium salt with trade name: GenX), result in detect- Ilyas, 2017). In addition, PFAS are frequently employed in indus- able levels of PFAS throughout drinking water in the United trial manufacturing processes due to their hydrophobicity and States (Rayne and Forest, 2009). According to the National stability, 2 key factors that contribute to their persistence in the Health and Nutrition Examination Survey, most people in the environment (Kovarova and Svobodova, 2008). Despite regula- United States and other industrialized countries have detect- tory efforts in the United States to phase out production of leg- able levels (median 10 ng/ml total) of PFAS in their blood acy PFAS perfluorooctanoic acid (PFOA) and perfluorooctanoic (NHANES, 2014). PFAS are detectable even after steady low-level VC The Author(s) 2020. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: [email protected] 1 2|PLACENTAL TROPHOBLAST MIGRATION AND INVASION exposure because of their long biological half-life. PFAS have (Manassas, Virginia). Cells were grown in Gibco RPMI 1640, sup- also been detected in both placenta (approximately 0.1–10 ng/g plemented with 10% fetal bovine serum, 1% penicillin/strepto- Downloaded from https://academic.oup.com/toxsci/advance-article-abstract/doi/10.1093/toxsci/kfaa043/5812793 by University of North Carolina at Chapel Hill user on 19 May 2020 wet weight) and cord blood in a number of studies worldwide mycin, and 1 mM sodium pyruvate at 37 Cin5%CO2. indicating that PFAS are prevalent, being retained in maternal serum, and crossing the placenta into the fetal circulation Resazurin cytotoxicity assay. Cells were seeded at 10 000 cells/ (Fisher et al., 2016; Lee et al., 2016; Mamsen et al., 2017; Spratlen well, incubated overnight, and treated with 0.01–100 000 ng/ml et al., 2019; Wang et al., 2016). PFOS, PFOA, GenX (Synquest Laboratories, Alachua, Florida) or Legacy PFAS are well documented for their role as develop- 10–100 ng/ml pertussis toxin (PTX; Millipore Sigma, St. Louis, mental and metabolic toxicants with impact on later life child- Missouri) for 24 h. Resazurin was then added to each well at a fi- ren’s health (Braun, 2017). There is also evidence of concern to nal concentration of 10 mg/ml, incubated for 4 h at 37Cin5% pregnant women, that PFAS are associated with detriments to CO2, and fluorescence read on a Promega (Madison, Wisconsin) the health of the pregnancy and to the developing fetus (Bach GloMax microplate spectrophotometer using 560 and 590 nm as et al., 2015; Darrow et al., 2013; Huang et al., 2019; Stein et al., the excitation and emission wavelength, respectively. Of all the 2009; Wikstro¨m et al., 2019). Specifically, placental PFOS content chemicals tested, only 100 000 ng/ml PFOS was cytotoxic over has been associated with the incidence of preeclampsia across 24 h. multiple studies (Darrow et al., 2013; Huang et al., 2019; Stein et al., 2009; Wikstro¨m et al., 2019). Placental, maternal serum, Migration and invasion. To measure trophoblast migration and in- and cord serum PFAS concentrations during pregnancy have vasion, an ACEA S16 Real-Time Cell Analyzer (ACEA, San Diego, also been correlated to low birth weight, which is often a conse- California) was utilized, which, using wells lined with gold quence of placental insufficiency, in multiple studies (Ashley- microelectrodes, measures the electrical resistance associated Martin et al., 2017; Rokoff et al., 2018; Sagiv et al., 2018; Valvi et al., with cell number and density. If done in conjunction with the 2017; Verner et al., 2015; Washino et al., 2009; Woods et al., 2017). traditional scratch assay, this setup allows for the collection of Little is known, however, about the mechanistic interactions be- migration and invasion data in real time without relying on mi- tween PFAS and the placenta as it pertains to pregnancy com- croscopy and image analysis (Al-Khayal et al., 2017; Bucur et al., plications such as preeclampsia. 2018; Ragone et al., 2017). For migration and invasion assays, As a tool to study the biological mechanisms underlying pre- cells were seeded at 25 000 cells/well in a 16-well E-Plate VIEW eclampsia, investigators can use placental cell lines to repro- 16 (ACEA) and allowed to adhere overnight. For invasion assays duce and examine trophoblast migration and invasion (Alvarez in particular, wells were coated with 100 mg/ml Matrigel and Chakraborty, 2011; Brooks and Fry, 2017; Zhang et al., (Corning, Corning, New York) the day before seeding. Scratches 2019b). Efficient exchange of nutrients, waste, and dissolved were generated 48 h postseeding when growth had plateaued gasses across the placenta requires sufficient maternal blood and the cells were 100% confluent. The day before scratching, flow in the villous space. This is accomplished through the cells were pretreated with PFAS (1000 ng/ml) for 24 h. This dose remodeling of the maternal endometrial spiral arteries, which is is biologically relevant as it is representative of median serum carried out by invasive extravillous trophoblasts (Anin et al., PFAS concentrations previously observed in occupationally ex- 2004; Lyall et al., 1999; Whitley and Cartwright, 2010). Defective posed populations (Fu et al., 2016; Zhou et al., 2014). On the day spiral artery transformation and shallow trophoblast invasion of the experiment, a scratch was generated in each well with a are both known histological features of preeclampsia 200 ml pipette tip, cells washed twice with culture medium. For (Chaiworapongsa et al., 2014; Falco et al., 2017; Lyall et al., 2013; migration assays, medium containing PFAS (1000 ng/ml) or PTX Silva and Serakides, 2016). The precise regulation of extravillous (10 ng/ml) was then added to each well (100 ml final volume). For trophoblast invasion is essential not only to placentation but invasion assays, scratched were filled in with 50 ml of treatment- also to fetal development. Environmental toxicants that inter- containing Matrigel solution. The concentration of Matrigel fere with the pathways regulating invasion can therefore poten- used in this step was 800 mg/ml, which was determined in a sep- tially be detrimental to maternal and fetal health during arate experiment to reduce cell movement without completely pregnancy
Load more

Recommended publications
  • Chemicals in the Fourth Report and Updated Tables Pdf Icon[PDF
    Chemicals in the Fourth National Report on Human Exposure to Environmental Chemicals: Updated Tables, March 2021 CDC’s Fourth National Report on Human Exposure to Environmental Chemicals: Updated Tables, March 2021 provides exposure data on the following chemicals or classes of chemicals. The Updated Tables contain cumulative data from national samples collected beginning in 1999–2000 and as recently as 2015-2016. Not all chemicals were measured in each national sample. The data tables are available at https://www.cdc.gov/exposurereport. An asterisk (*) indicates the chemical has been added since publication of the Fourth National Report on Human Exposure to Environmental Chemicals in 2009. Adducts of Hemoglobin Acrylamide Formaldehyde* Glycidamide Tobacco Alkaloids and Metabolites Anabasine* Anatabine* Cotinine Cotinine-n-oxide* Hydroxycotinine* Trans-3’-hydroxycotinine* 1-(3-Pyridyl)-1-butanol-4-carboxylic acid* Nicotine* Nicotine-N’-oxide* Nornicotine* Tobacco-Specific Nitrosamines (TSNAs) N’-Nitrosoanabasine (NAB)* N’-Nitrosoanatabine (NAT)* N’-Nitrosonornicotine (NNN)* Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol) (NNAL)* Volatile N-nitrosamines (VNAs) N-Nitrosodiethylamine (NDEA)* N-Nitrosoethylmethylamine (NMEA)* N-Nitrosomorpholine (NMOR)* N-Nitrosopiperidine (NPIP)* N-Nitrosopyrrolidine (NPYR)* Disinfection By-Products Bromodichloromethane Dibromochloromethane Tribromomethane (Bromoform) Trichloromethane (Chloroform) Personal Care and Consumer Product Chemicals and Metabolites Benzophenone-3 Bisphenol A Bisphenol F* Bisphenol
    [Show full text]
  • Pfoa) Or Perfluorooctane Sulfonate (Pfos
    National Toxicology Program NTP U.S. Department of Health and Human Services NTP Monograph Immunotoxicity Associated with Exposure to Perfluorooctanoic Acid or Perfluorooctane Sulfonate September 2016 NTP MONOGRAPH ON IMMUNOTOXICITY ASSOCIATED WITH EXPOSURE TO PERFLUOROOCTANOIC ACID (PFOA) OR PERFLUOROOCTANE SULFONATE (PFOS) September, 2016 Office of Health Assessment and Translation Division of the National Toxicology Program National Institute of Environmental Health Sciences National Institutes of Health U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Systematic Review of Immunotoxicity Associated with Exposure to PFOA or PFOS TABLE OF CONTENTS Table of Contents ...............................................................................................................................II List of Table and Figures ................................................................................................................... IV Abstract ............................................................................................................................................. 1 Peer Review Of The Draft NTP Monograph ......................................................................................... 2 Peer-Review Panel .............................................................................................................................. 2 Introduction ...................................................................................................................................... 3 Objective and Specific Aims ...............................................................................................................
    [Show full text]
  • PFAS MCL Technical Support Document
    ATTACHMENT 1 New Hampshire Department of Environmental Services Technical Background Report for the June 2019 Proposed Maximum Contaminant Levels (MCLs) and Ambient Groundwater Quality Standards (AGQSs) for Perfluorooctane sulfonic Acid (PFOS), Perfluorooctanoic Acid (PFOA), Perfluorononanoic Acid (PFNA), and Perfluorohexane sulfonic Acid (PFHxS) And Letter from Dr. Stephen M. Roberts, Ph.D. dated 6/25/2019 – Findings of Peer Review Conducted on Technical Background Report June 28, 2019 New Hampshire Department of Environmental Services Technical Background Report for the June 2019 Proposed Maximum Contaminant Levels (MCLs) and Ambient Groundwater Quality Standards (AGQSs) for Perfluorooctane sulfonic Acid (PFOS), Perfluorooctanoic Acid (PFOA), Perfluorononanoic Acid (PFNA), and Perfluorohexane sulfonic Acid (PFHxS) June 28, 2019 Table of Contents Abbreviations ................................................................................................................................................. i Acknowledgements ...................................................................................................................................... iii Section I. Executive Summary ....................................................................................................................... 1 Section II. Introduction ................................................................................................................................. 2 Section III. Reference Dose Derivation ........................................................................................................
    [Show full text]
  • Health Effects Support Document for Perfluorooctanoic Acid (PFOA)
    United States Office of Water EPA 822-R-16-003 Environmental Protection Mail Code 4304T May 2016 Agency Health Effects Support Document for Perfluorooctanoic Acid (PFOA) Perfluorooctanoic Acid – May 2016 i Health Effects Support Document for Perfluorooctanoic Acid (PFOA) U.S. Environmental Protection Agency Office of Water (4304T) Health and Ecological Criteria Division Washington, DC 20460 EPA Document Number: 822-R-16-003 May 2016 Perfluorooctanoic Acid – May 2016 ii BACKGROUND The Safe Drinking Water Act (SDWA), as amended in 1996, requires the Administrator of the U.S. Environmental Protection Agency (EPA) to periodically publish a list of unregulated chemical contaminants known or anticipated to occur in public water systems and that may require regulation under SDWA. The SDWA also requires the Agency to make regulatory determinations on at least five contaminants on the Contaminant Candidate List (CCL) every 5 years. For each contaminant on the CCL, before EPA makes a regulatory determination, the Agency needs to obtain sufficient data to conduct analyses on the extent to which the contaminant occurs and the risk it poses to populations via drinking water. Ultimately, this information will assist the Agency in determining the most appropriate course of action in relation to the contaminant (e.g., developing a regulation to control it in drinking water, developing guidance, or deciding not to regulate it). The PFOA health assessment was initiated by the Office of Water, Office of Science and Technology in 2009. The draft Health Effects Support Document for Perfluoroctanoic Acid (PFOA) was completed in 2013 and released for public comment in February 2014.
    [Show full text]
  • Perfluorooctane Sulfonate (PFOS) and Perfluorooctanoic Acid (PFOA) November 2017 TECHNICAL FACT SHEET – PFOS and PFOA
    Technical Fact Sheet – Perfluorooctane Sulfonate (PFOS) and Perfluorooctanoic Acid (PFOA) November 2017 TECHNICAL FACT SHEET – PFOS and PFOA Introduction At a Glance This fact sheet, developed by the U.S. Environmental Protection Agency Manmade chemicals not (EPA) Federal Facilities Restoration and Reuse Office (FFRRO), provides a naturally found in the summary of two contaminants of emerging concern, perfluorooctane environment. sulfonate (PFOS) and perfluorooctanoic acid (PFOA), including physical and Fluorinated compounds that chemical properties; environmental and health impacts; existing federal and repel oil and water. state guidelines; detection and treatment methods; and additional sources of information. This fact sheet is intended for use by site managers who may Used in a variety of industrial address these chemicals at cleanup sites or in drinking water supplies and and consumer products, such for those in a position to consider whether these chemicals should be added as carpet and clothing to the analytical suite for site investigations. treatments and firefighting foams. PFOS and PFOA are part of a larger group of chemicals called per- and Extremely persistent in the polyfluoroalkyl substances (PFASs). PFASs, which are highly fluorinated environment. aliphatic molecules, have been released to the environment through Known to bioaccumulate in industrial manufacturing and through use and disposal of PFAS-containing humans and wildlife. products (Liu and Mejia Avendano 2013). PFOS and PFOA are the most Readily absorbed after oral widely studied of the PFAS chemicals. PFOS and PFOA are persistent in the exposure. Accumulate environment and resistant to typical environmental degradation processes. primarily in the blood serum, As a result, they are widely distributed across all trophic levels and are found kidney and liver.
    [Show full text]
  • Microbiota and Obesogens: Environmental Regulators of Fat Storage
    Microbiota and obesogens: environmental regulators of fat storage John F. Rawls, Ph.D. Department of Molecular Genetics & Microbiology Center for Genomics of Microbial Systems Duke University School of Medicine Seminar outline 1. Introduction to the microbiota 2. Microbiota as environmental factors in obesity 3. Obesogens as environmental factors in obesity Seeing and understanding the unseen Antonie van Leewenhoek 1620’s: Described differences between microbes associated with teeth & feces during health & disease. Louis Pasteur 1850’s: Helps establish the “germ theory” of disease. 1885: Predicts that germ-free animals can not survive without “common microorganisms”. Culture-independent analysis of bacterial communities using 16S rRNA gene sequencing 16S rRNA 16S SSU rRNA 16S rRNA gene V1 V2 V3 V4 V5 V6 V7 V8 V9 Culture-independent analysis of bacterial communities using 16S rRNA gene sequencing plantbiology.siu.edu Phylogenetic analysis of 16S rRNA genes revealed 3 domains and a vast unappreciated diversity of microbial life You are here Carl Woese Glossary • Microbiota / microflora: the microorganisms of a particular site, habitat, or period of time. • Microbiome: the collective genomes of the microorganisms within a microbiota. • Germ-free / axenic: of a culture that is free from living organisms other than the host species. • Gnotobiotic: of an environment for rearing organisms in which all the microorganisms are either excluded or known. Current techniques for microbiome profiling Microbial community Morgan et al. (2012) Trends in
    [Show full text]
  • Perfluorooctanoic Acid (Pfoa) and Perfluorooctanesulfonic Acid (Pfos)
    WATER QUALITY FACT SHEET: PERFLUOROOCTANOIC ACID (PFOA) AND PERFLUOROOCTANESULFONIC ACID (PFOS) Chemical Properties: • PFOA and PFOS are fluorinated organic chemicals that are part of a larger man-made chemical group referred to as per- and polyfluoroalkyl substances (PFAS), which are resistant to heat, water, and oil. • The chemicals have been used in consumer products such as carpets, clothing, fabrics for furniture, paper packaging for food, and other materials (e.g., cookware) designed to be waterproof, stain- resistant or non-stick. • They also have been used in fire-retarding foam at airfields, military bases, and various industrial processes. • PFOA and PFOS have been the most extensively produced and studied PFAS. PFAS also includes GenX chemicals and perfluorobutane sulfonic acid (PFBS) which require further study. • PFAS tends to accumulate in groundwater with contamination typically localized and associated with facilities where the chemicals were produced or used to manufacture other products. Health Concerns: • In 2016, the United States Environmental Protection Agency (USEPA) issued a lifetime health advisory for PFOA and PFOS for drinking water. Municipalities were advised that they should notify their customers of the presence of levels over 70 ppt (0.07 µg/L) in community water supplies. • Studies indicate that PFOA and PFOS may result in adverse health effects including developmental effects to fetuses during pregnancy or breastfed infants, cancer, liver effects, immune effects, thyroid effects, and cholesterol changes. Regulatory Considerations: • The USEPA has not regulated PFOA and PFOS. There is no Federal MCL or MCLG. • In August 2019, the California State Water Resources Control Board Division of Drinking Water (DDW) updated notification levels for PFOA and PFOS from 14 ppt to 5.1 ppt for PFOA and from 13 ppt to 6.5 ppt for PFOS.
    [Show full text]
  • Perfluorooctanoic Acid Levels, Nuclear Receptor Gene Polymorphisms, And
    www.nature.com/scientificreports OPEN Associations among perfuorooctanesulfonic/ perfuorooctanoic acid levels, nuclear receptor gene polymorphisms, and lipid levels in pregnant women in the Hokkaido study Sumitaka Kobayashi1, Fumihiro Sata1,2, Houman Goudarzi1,3, Atsuko Araki1, Chihiro Miyashita1, Seiko Sasaki4, Emiko Okada5, Yusuke Iwasaki6, Tamie Nakajima7 & Reiko Kishi1* The efect of interactions between perfuorooctanesulfonic (PFOS)/perfuorooctanoic acid (PFOA) levels and nuclear receptor genotypes on fatty acid (FA) levels, including those of triglycerides, is not clear understood. Therefore, in the present study, we aimed to analyse the association of PFOS/PFOA levels and single-nucleotide polymorphisms (SNPs) in nuclear receptors with FA levels in pregnant women. We analysed 504 mothers in a birth cohort between 2002 and 2005 in Japan. Serum PFOS/ PFOA and FA levels were measured using liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry. Maternal genotypes in PPARA (rs1800234; rs135561), PPARG (rs3856806), PPARGC1A (rs2970847; rs8192678), PPARD (rs1053049; rs2267668), CAR (rs2307424; rs2501873), LXRA (rs2279238) and LXRB (rs1405655; rs2303044; rs4802703) were analysed. When gene-environment interaction was considered, PFOS exposure (log10 scale) decreased palmitic, palmitoleic, and oleic acid levels (log10 scale), with the observed β in the range of − 0.452 to − 0.244; PPARGC1A (rs8192678) and PPARD (rs1053049; rs2267668) genotypes decreased triglyceride, palmitic, palmitoleic, and oleic acid levels, with the observed β in the range of − 0.266 to − 0.176. Interactions between PFOS exposure and SNPs were signifcant for palmitic acid (Pint = 0.004 to 0.017). In conclusion, the interactions between maternal PFOS levels and PPARGC1A or PPARD may modify maternal FA levels. Te genetic makeup of a person and the environmental factors might be responsible for regulating the levels of serum lipids, such as fatty acids (FA) and triglycerides (TG)1.
    [Show full text]
  • Environmental Factors, Epigenetics, and Developmental Origin of Reproductive Disorders
    HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Reprod Manuscript Author Toxicol. Author Manuscript Author manuscript; available in PMC 2018 March 01. Published in final edited form as: Reprod Toxicol. 2017 March ; 68: 85–104. doi:10.1016/j.reprotox.2016.07.011. Environmental Factors, Epigenetics, and Developmental Origin of Reproductive Disorders Shuk-Mei Hoa,b,c,d,*, Ana Cheonga,b, Margaret A. Adgente, Jennifer Veeversa,c, Alisa A. Suenf,g, Neville N.C. Tama,b,c, Yuet-Kin Leunga,b,c, Wendy N. Jeffersonf, and Carmen J. Williamsf,* aDepartment of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America bCenter for Environmental Genetics, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America cCincinnati Cancer Center, Cincinnati, Ohio, United States of America dCincinnati Veteran Affairs Hospital Medical Center, Cincinnati, Ohio, United States of America eDepartment of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America fReproductive Medicine Group, Reproductive & Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America gCurriculum in Toxicology, UNC Chapel Hill, Chapel Hill, North Carolina, United States of America Abstract Sex-specific differentiation, development, and function of the reproductive system are largely dependent on steroid hormones. For this reason, developmental exposure
    [Show full text]
  • Perfluorooctanoic Acid (PFOA)
    PERFLUOROOCTANOIC ACID 1. Exposure Data 1.1.2 Structural and molecular formulae, and relative molecular mass: straight-chain 1.1 Identification of the agent isomer 1.1.1 Nomenclature F FFF F F F O F Chem. Abstr. Serv. Reg. No.: 335-67-1 OH Chem. Abstr. Serv. Name: Perfluorooctanoic FFF F F F F acid Molecular formula: C8HF15O2 IUPAC Name: 2,2,3,3,4,4,5,5,6,6,7,7,8,8,8- Relative molecular mass: 414 pentadecafluorooctanoic acid Synonyms: PFOA; pentadecafluoro-1-octan - 1.1.3 Chemical and physical properties of the oic acid; pentadecafluoro-n-octanoic acid; pure substance: straight-chain isomer pentadecaflurooctanoic acid; perfluoro- caprylic acid; perfluoroctanoic acid; From HSDB (2014), unless otherwise perfluoroheptanecarboxylic acid; APFO; indicated ammonium perfluorooctanoate Description: White to off-white powder Isomers and Salts: There are 39 possible struc- Boiling point: 192.4 °C tural isomers of pentadecafluorooctanoic acid (1 with chain length 8, 5 with chain Melting point: 54.3 °C length 7, 13 with chain length 6, 16 with chain Density: 1.792 g/cm3 at 20 °C length 5, and 4 with chain length 4). These Solubility: 9.5 g/L in water at 25 °C isomers can also exist as the ammonium, Vapour pressure: 0.0023 kPa at 20 °C (extrap- sodium, or potassium salt (Nielsen, 2012). olated); 0.127 kPa at 59.25 °C (measured) Fig. 1.1 presents the few isomers and salts (ATSDR, 2009); 0.070 kPa at 25 °C that have Chemical Abstracts Service (CAS) Stability: When heated to decomposition it references.
    [Show full text]
  • Development of Novel Synthetic Routes to the Epoxyketooctadecanoic Acids
    DEVELOPMENT OF NOVEL SYNTHETIC ROUTES TO THE EPOXYKETOOCTADECANOIC ACIDS (EKODES) AND THEIR BIOLOGICAL EVALUATION AS ACTIVATORS OF THE PPAR FAMILY OF NUCLEAR RECEPTORS By ROOZBEH ESKANDARI Submitted in partial fulfillment of the requirements for The Degree of Doctor of Philosophy Thesis Advisor: Gregory P. Tochtrop, Ph.D. Department of Chemistry CASE WESTERN RESERVE UNIVERSITY January, 2016 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of ROOZBEH ESKANDARI Candidate for the Ph.D degree *. (signed) Anthony J. Pearson, PhD (Chair of the committee) Gregory P. Tochtrop, PhD (Advisor) Michael G. Zagorski, PhD Blanton S. Tolbert, PhD Witold K. Surewicz, PhD (Department of Physiology and Biophysics) (date) 14th July, 2015 *We also certify that written approval has been obtained for any proprietary material contained therein. I dedicate this work to my sister Table of Contents Table of Contents ........................................................................................................................ i List of Tables .............................................................................................................................. vi List of Figures ........................................................................................................................... vii List of Schemes .......................................................................................................................... ix Acknowledgements ..................................................................................................................
    [Show full text]
  • Perfluorooctanoic Acid Exposure Alters Polyunsaturated Fatty Acid
    Chemosphere 158 (2016) 143e153 Contents lists available at ScienceDirect Chemosphere journal homepage: www.elsevier.com/locate/chemosphere Perfluorooctanoic acid exposure alters polyunsaturated fatty acid composition, induces oxidative stress and activates the AKT/AMPK pathway in mouse epididymis ** * Yin Lu a, Yitao Pan a, Nan Sheng a, Allan Z. Zhao b, , Jiayin Dai a, a Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China b Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, 210029, China highlights PFOA exposure altered polyunsaturated fatty acid composition in epididymides. Triglyceride level and AKT/AMPK signaling strength were detected. PFOA exposure resulted in oxidative stress in the epididymis. article info abstract Article history: Perfluorooctanoic acid (PFOA) is a degradation-resistant compound with a carbon-fluorine bond. Received 25 February 2016 Although PFOA emissions have been reduced since 2000, it remains persistent in the environment. Received in revised form Several studies on laboratory animals indicate that PFOA exposure can impact male fertility. Here, adult 2 May 2016 male mice received either PFOA (1.25, 5 or 20 mg/kg/d) or an equal volume of water for 28 d consec- Accepted 22 May 2016 utively. PFOA accumulated in the epididymis in a dose-dependent manner and resulted in reduced Available online 1 June 2016 epididymis weight, lower levels of triglycerides (TG), cholesterol (CHO), and free fatty acids (FFA), and Handling Editor: A. Gies activated AKT/AMPK signaling in the epididymis. Altered polyunsaturated fatty acid (PUFA) composi- tions, such as a higher arachidonic acid:linoleic acid (AA:LA) ratio, concomitant with excessive oxidative Keywords: stress, as demonstrated by increased malonaldehyde (MDA) and decreased glutathione peroxidase (GSH- PUFA Px) in the epididymis, were observed in epididymis tissue following treatment with PFOA.
    [Show full text]