Urban PM2.5 Induces Cellular Toxicity, Hormone Dysregulation, Oxidative Damage, Inflammation, and Mitochondrial Interference in the HRT8 Trophoblast Cell Line
(2020) In Frontiers in Endocrinology 11.- Abstract
- Objective: Epidemiological studies have found air pollution to be a driver of adverse pregnancy outcomes, including gestational diabetes, low term birth weight and preeclampsia. It is unknown what biological mechanisms are involved in this process. A first trimester trophoblast cell line (HTR-8/SVneo) was exposed to various concentrations of PM2.5 (PM2.5) in order to elucidate the effect of urban particulate matter (PM) of size <2.5 μm on placental function. Methods: PM2.5 were collected at a site representative of urban traffic and dispersed in cell media by indirect and direct sonication. The HTR-8 cells were grown under standard conditions. Cellular uptake was studied after 24 and 48 h of exposure by transmission electron microscopy... (More)
- Objective: Epidemiological studies have found air pollution to be a driver of adverse pregnancy outcomes, including gestational diabetes, low term birth weight and preeclampsia. It is unknown what biological mechanisms are involved in this process. A first trimester trophoblast cell line (HTR-8/SVneo) was exposed to various concentrations of PM2.5 (PM2.5) in order to elucidate the effect of urban particulate matter (PM) of size <2.5 μm on placental function. Methods: PM2.5 were collected at a site representative of urban traffic and dispersed in cell media by indirect and direct sonication. The HTR-8 cells were grown under standard conditions. Cellular uptake was studied after 24 and 48 h of exposure by transmission electron microscopy (TEM). The secretion of human chorionic gonadotropin (hCG), progesterone, and Interleukin-6 (IL-6) was measured by ELISA. Changes in membrane integrity and H2O2 production were analyzed using the CellToxTM Green Cytotoxicity and ROSGloTM assays. Protease activity was evaluated by MitoToxTM assay. Mitochondrial function was assessed through high resolution respirometry in an Oroboros O2k-FluoRespirometer, and mitochondrial content was quantified by citrate synthase activity. Results: TEM analysis depicted PM2.5 cellular uptake and localization of the PM2.5 to the mitochondria after 24 h. The cells showed aggregated cytoskeleton and generalized necrotic appearance, such as chromatin condensation, organelle swelling and signs of lost membrane integrity. The mitochondria displayed vacuolization and disruption of cristae morphology. At 48 h exposure, a significant drop in hCG secretion and a significant increase in progesterone secretion and IL-6 production occurred. At 48 h exposure, a five-fold increase in protease activity and a significant alteration of H2O2 production was observed. The HTR-8 cells exhibited evidence of increased cytotoxicity with increasing exposure time and dose of PM2.5. No significant difference in mitochondrial respiration or mitochondrial mass could be demonstrated. Conclusion: Following exposure to air pollution, intracellular accumulation of PM may contribute to the placental dysfunction associated with pregnancy outcomes, such as preeclampsia and intrauterine growth restriction, through their direct and indirect effects on trophoblast protein secretion, hormone regulation, inflammatory response, and mitochondrial interference. (Less)
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- author
- organization
-
- Obstetrics and Gynaecology (Lund)
- Ergonomics and Aerosol Technology
- NanoLund: Centre for Nanoscience
- Mitochondrial Medicine (research group)
- MultiPark: Multidisciplinary research focused on Parkinson´s disease
- Nuclear physics
- Applied Mass Spectrometry in Environmental Medicine (research group)
- Division of Occupational and Environmental Medicine, Lund University
- Genetic Occupational and Environmental Medicine (research group)
- EpiHealth: Epidemiology for Health
- Planetary Health (research group)
- publishing date
- 2020-03-12
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Frontiers in Endocrinology
- volume
- 11
- article number
- 75
- publisher
- Frontiers Media S. A.
- external identifiers
-
- scopus:85082665203
- pmid:32226408
- ISSN
- 1664-2392
- DOI
- 10.3389/fendo.2020.00075
- project
- Mitochondrial dysfunction in drug and chemical toxicity: mechanism, target identification and therapeutic development
- language
- English
- LU publication?
- yes
- id
- c8b0a478-6fc4-4e25-8332-b746f2c869ce
- date added to LUP
- 2020-04-17 15:37:56
- date last changed
- 2023-11-20 02:54:08
@article{c8b0a478-6fc4-4e25-8332-b746f2c869ce, abstract = {{Objective: Epidemiological studies have found air pollution to be a driver of adverse pregnancy outcomes, including gestational diabetes, low term birth weight and preeclampsia. It is unknown what biological mechanisms are involved in this process. A first trimester trophoblast cell line (HTR-8/SVneo) was exposed to various concentrations of PM2.5 (PM2.5) in order to elucidate the effect of urban particulate matter (PM) of size <2.5 μm on placental function. Methods: PM2.5 were collected at a site representative of urban traffic and dispersed in cell media by indirect and direct sonication. The HTR-8 cells were grown under standard conditions. Cellular uptake was studied after 24 and 48 h of exposure by transmission electron microscopy (TEM). The secretion of human chorionic gonadotropin (hCG), progesterone, and Interleukin-6 (IL-6) was measured by ELISA. Changes in membrane integrity and H2O2 production were analyzed using the CellToxTM Green Cytotoxicity and ROSGloTM assays. Protease activity was evaluated by MitoToxTM assay. Mitochondrial function was assessed through high resolution respirometry in an Oroboros O2k-FluoRespirometer, and mitochondrial content was quantified by citrate synthase activity. Results: TEM analysis depicted PM2.5 cellular uptake and localization of the PM2.5 to the mitochondria after 24 h. The cells showed aggregated cytoskeleton and generalized necrotic appearance, such as chromatin condensation, organelle swelling and signs of lost membrane integrity. The mitochondria displayed vacuolization and disruption of cristae morphology. At 48 h exposure, a significant drop in hCG secretion and a significant increase in progesterone secretion and IL-6 production occurred. At 48 h exposure, a five-fold increase in protease activity and a significant alteration of H2O2 production was observed. The HTR-8 cells exhibited evidence of increased cytotoxicity with increasing exposure time and dose of PM2.5. No significant difference in mitochondrial respiration or mitochondrial mass could be demonstrated. Conclusion: Following exposure to air pollution, intracellular accumulation of PM may contribute to the placental dysfunction associated with pregnancy outcomes, such as preeclampsia and intrauterine growth restriction, through their direct and indirect effects on trophoblast protein secretion, hormone regulation, inflammatory response, and mitochondrial interference.}}, author = {{Nääv, Åsa and Erlandsson, Lena and Isaxon, Christina and Åsander Frostner, Eleonor and Ehinger, Johannes and Elmer, Eskil and Sporre, Moa and Krais, Annette and Strandberg, Bo and Lundh, Thomas and Malmqvist, Ebba and Hansson, Stefan}}, issn = {{1664-2392}}, language = {{eng}}, month = {{03}}, publisher = {{Frontiers Media S. A.}}, series = {{Frontiers in Endocrinology}}, title = {{Urban PM2.5 Induces Cellular Toxicity, Hormone Dysregulation, Oxidative Damage, Inflammation, and Mitochondrial Interference in the HRT8 Trophoblast Cell Line}}, url = {{http://dx.doi.org/10.3389/fendo.2020.00075}}, doi = {{10.3389/fendo.2020.00075}}, volume = {{11}}, year = {{2020}}, }