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
N1 - Funding Information:
This study is supported by the NICHD (grant number 1R01HD084532-01A1 ) to R Menon.
Funding Information:
This study is supported by the NICHD (grant number 1R01HD084532-01A1) to R Menon.Authors acknowledge support by all the staff from the Maternal-Fetal Medicine and Perinatal Research Laboratory, University of Texas Medical Branch at Galveston (UTMB), TX, USA. Mass spec was performed at the UTMB Mass Spectrometry Facility with the support and guidance from Drs. William Russell and Xuemei Luo. Cryo-EM was performed at the electron microscopy core laboratory at UTMB with support and guidance from Michael Woodson, Ph.D.
Publisher Copyright:
© 2019 Elsevier Ltd
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
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U2 - 10.1016/j.placenta.2019.10.008
DO - 10.1016/j.placenta.2019.10.008
M3 - Article
C2 - 31675489
AN - SCOPUS:85074030582
SN - 0143-4004
VL - 89
SP - 42
EP - 49
JO - Placenta
JF - Placenta
ER -