Environmental pollutant induced cellular injury is reflected in exosomes from placental explants

Samantha Sheller-Miller, Enkhtuya Radnaa, Yuko Arita, Darios Getahun, Richard J. Jones, Morgan R. Peltier, Ramkumar Menon

Research output: Contribution to journalArticle

Abstract

Introduction: Exosomes are intercellular signaling vesicles whose cargo reflects the physiological status of the cell of their origin and can regulate gene expression in other tissues. Polybrominated diphenyl ethers (PBDEs) and bisphenols (A [BPA], Tetrabromobisphenol A [TBBPA], and 2,4,6-Tribromophenol [TBP]) are common environmental pollutants known to increase the risk for spontaneous preterm birth (PTB). We hypothesized that placental exposure to these environmental pollutants causes exosome cargo changes that reflect exposure associated placental response. Methods: Full-term, C-section placenta explants were treated with PBDE congeners (47, 100, 153, 209), TBBPA, TBP or BPA for 24 h. Exosomes were isolated from media by sequential ultracentrifugation and purified by size exclusion chromatography. Exosomes were characterized by electron microscopy, nanoparticle tracking analysis and Western blot. Proteomics identified differentially expressed exosomal proteins and Ingenuity pathway analysis (IPA) determined biological functions and pathways represented by identified proteins. Results: Regardless of treatment, placental expressed exosomes markers (PLAP, CD9, CD63, 81 and ALIX), had a size distribution between 50 and 175 nm and were present in the conditioned medium at 5–8 x 1011 exosomes/mL. Proteomic analysis identified 2598 proteins which demonstrated that specific pollutants caused differential expression of specific proteins, including alarmin, High Mobility Group Box 1 (HMGB1), MAPK14 (p38 MAPK) and GSK3β. IPA revealed an inhibition of pathways associated with cell survival, tissue repair and proliferation, as well as activation of cell death pathways (e.g. necrosis). Conclusion: Environmental exposure of placental explants did not change the quantity of exosomes or their characteristics. However, exosome cargo composition exposed to some environment pollutants may be involved in placental nuclear and cellular injury and inflammation.

Original languageEnglish (US)
Pages (from-to)42-49
Number of pages8
JournalPlacenta
Volume89
DOIs
StatePublished - Jan 1 2020

Fingerprint

Exosomes
Environmental Pollutants
Wounds and Injuries
Halogenated Diphenyl Ethers
Proteomics
Mitogen-Activated Protein Kinase 14
Proteins
Ultracentrifugation
Premature Birth
Environmental Exposure
p38 Mitogen-Activated Protein Kinases
Conditioned Culture Medium
Nanoparticles
Placenta
Gel Chromatography
Cell Survival
Electron Microscopy
Cell Death
Necrosis
Western Blotting

Keywords

  • Extracellular vesicles
  • Flame retardants
  • Inflammation
  • Persistent organic pollutants
  • Preterm birth

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology
  • Developmental Biology

Cite this

Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. / Sheller-Miller, Samantha; Radnaa, Enkhtuya; Arita, Yuko; Getahun, Darios; Jones, Richard J.; Peltier, Morgan R.; Menon, Ramkumar.

In: Placenta, Vol. 89, 01.01.2020, p. 42-49.

Research output: Contribution to journalArticle

Sheller-Miller, Samantha ; Radnaa, Enkhtuya ; Arita, Yuko ; Getahun, Darios ; Jones, Richard J. ; Peltier, Morgan R. ; Menon, Ramkumar. / Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. In: Placenta. 2020 ; Vol. 89. pp. 42-49.
@article{55128a7c0a2f4f99a18aa3631b68d9ca,
title = "Environmental pollutant induced cellular injury is reflected in exosomes from placental explants",
abstract = "Introduction: Exosomes are intercellular signaling vesicles whose cargo reflects the physiological status of the cell of their origin and can regulate gene expression in other tissues. Polybrominated diphenyl ethers (PBDEs) and bisphenols (A [BPA], Tetrabromobisphenol A [TBBPA], and 2,4,6-Tribromophenol [TBP]) are common environmental pollutants known to increase the risk for spontaneous preterm birth (PTB). We hypothesized that placental exposure to these environmental pollutants causes exosome cargo changes that reflect exposure associated placental response. Methods: Full-term, C-section placenta explants were treated with PBDE congeners (47, 100, 153, 209), TBBPA, TBP or BPA for 24 h. Exosomes were isolated from media by sequential ultracentrifugation and purified by size exclusion chromatography. Exosomes were characterized by electron microscopy, nanoparticle tracking analysis and Western blot. Proteomics identified differentially expressed exosomal proteins and Ingenuity pathway analysis (IPA) determined biological functions and pathways represented by identified proteins. Results: Regardless of treatment, placental expressed exosomes markers (PLAP, CD9, CD63, 81 and ALIX), had a size distribution between 50 and 175 nm and were present in the conditioned medium at 5–8 x 1011 exosomes/mL. Proteomic analysis identified 2598 proteins which demonstrated that specific pollutants caused differential expression of specific proteins, including alarmin, High Mobility Group Box 1 (HMGB1), MAPK14 (p38 MAPK) and GSK3β. IPA revealed an inhibition of pathways associated with cell survival, tissue repair and proliferation, as well as activation of cell death pathways (e.g. necrosis). Conclusion: Environmental exposure of placental explants did not change the quantity of exosomes or their characteristics. However, exosome cargo composition exposed to some environment pollutants may be involved in placental nuclear and cellular injury and inflammation.",
keywords = "Extracellular vesicles, Flame retardants, Inflammation, Persistent organic pollutants, Preterm birth",
author = "Samantha Sheller-Miller and Enkhtuya Radnaa and Yuko Arita and Darios Getahun and Jones, {Richard J.} and Peltier, {Morgan R.} and Ramkumar Menon",
year = "2020",
month = "1",
day = "1",
doi = "10.1016/j.placenta.2019.10.008",
language = "English (US)",
volume = "89",
pages = "42--49",
journal = "Placenta",
issn = "0143-4004",
publisher = "W.B. Saunders Ltd",

}

TY - JOUR

T1 - Environmental pollutant induced cellular injury is reflected in exosomes from placental explants

AU - Sheller-Miller, Samantha

AU - Radnaa, Enkhtuya

AU - Arita, Yuko

AU - Getahun, Darios

AU - Jones, Richard J.

AU - Peltier, Morgan R.

AU - Menon, Ramkumar

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Introduction: Exosomes are intercellular signaling vesicles whose cargo reflects the physiological status of the cell of their origin and can regulate gene expression in other tissues. Polybrominated diphenyl ethers (PBDEs) and bisphenols (A [BPA], Tetrabromobisphenol A [TBBPA], and 2,4,6-Tribromophenol [TBP]) are common environmental pollutants known to increase the risk for spontaneous preterm birth (PTB). We hypothesized that placental exposure to these environmental pollutants causes exosome cargo changes that reflect exposure associated placental response. Methods: Full-term, C-section placenta explants were treated with PBDE congeners (47, 100, 153, 209), TBBPA, TBP or BPA for 24 h. Exosomes were isolated from media by sequential ultracentrifugation and purified by size exclusion chromatography. Exosomes were characterized by electron microscopy, nanoparticle tracking analysis and Western blot. Proteomics identified differentially expressed exosomal proteins and Ingenuity pathway analysis (IPA) determined biological functions and pathways represented by identified proteins. Results: Regardless of treatment, placental expressed exosomes markers (PLAP, CD9, CD63, 81 and ALIX), had a size distribution between 50 and 175 nm and were present in the conditioned medium at 5–8 x 1011 exosomes/mL. Proteomic analysis identified 2598 proteins which demonstrated that specific pollutants caused differential expression of specific proteins, including alarmin, High Mobility Group Box 1 (HMGB1), MAPK14 (p38 MAPK) and GSK3β. IPA revealed an inhibition of pathways associated with cell survival, tissue repair and proliferation, as well as activation of cell death pathways (e.g. necrosis). Conclusion: Environmental exposure of placental explants did not change the quantity of exosomes or their characteristics. However, exosome cargo composition exposed to some environment pollutants may be involved in placental nuclear and cellular injury and inflammation.

AB - Introduction: Exosomes are intercellular signaling vesicles whose cargo reflects the physiological status of the cell of their origin and can regulate gene expression in other tissues. Polybrominated diphenyl ethers (PBDEs) and bisphenols (A [BPA], Tetrabromobisphenol A [TBBPA], and 2,4,6-Tribromophenol [TBP]) are common environmental pollutants known to increase the risk for spontaneous preterm birth (PTB). We hypothesized that placental exposure to these environmental pollutants causes exosome cargo changes that reflect exposure associated placental response. Methods: Full-term, C-section placenta explants were treated with PBDE congeners (47, 100, 153, 209), TBBPA, TBP or BPA for 24 h. Exosomes were isolated from media by sequential ultracentrifugation and purified by size exclusion chromatography. Exosomes were characterized by electron microscopy, nanoparticle tracking analysis and Western blot. Proteomics identified differentially expressed exosomal proteins and Ingenuity pathway analysis (IPA) determined biological functions and pathways represented by identified proteins. Results: Regardless of treatment, placental expressed exosomes markers (PLAP, CD9, CD63, 81 and ALIX), had a size distribution between 50 and 175 nm and were present in the conditioned medium at 5–8 x 1011 exosomes/mL. Proteomic analysis identified 2598 proteins which demonstrated that specific pollutants caused differential expression of specific proteins, including alarmin, High Mobility Group Box 1 (HMGB1), MAPK14 (p38 MAPK) and GSK3β. IPA revealed an inhibition of pathways associated with cell survival, tissue repair and proliferation, as well as activation of cell death pathways (e.g. necrosis). Conclusion: Environmental exposure of placental explants did not change the quantity of exosomes or their characteristics. However, exosome cargo composition exposed to some environment pollutants may be involved in placental nuclear and cellular injury and inflammation.

KW - Extracellular vesicles

KW - Flame retardants

KW - Inflammation

KW - Persistent organic pollutants

KW - Preterm birth

UR - http://www.scopus.com/inward/record.url?scp=85074030582&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85074030582&partnerID=8YFLogxK

U2 - 10.1016/j.placenta.2019.10.008

DO - 10.1016/j.placenta.2019.10.008

M3 - Article

AN - SCOPUS:85074030582

VL - 89

SP - 42

EP - 49

JO - Placenta

JF - Placenta

SN - 0143-4004

ER -