Reactive oxygen species from mitochondria impacts trophoblast fusion and the production of endocrine hormones by syncytiotrophoblasts.
Cell Fusion
Cells, Cultured
Female
Humans
Membrane Potential, Mitochondrial
/ drug effects
Mitochondria
/ metabolism
Oxidative Stress
/ drug effects
Placental Hormones
/ metabolism
Pregnancy
Reactive Oxygen Species
/ metabolism
Rotenone
/ pharmacology
Signal Transduction
/ drug effects
Trophoblasts
/ drug effects
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
07
05
2019
accepted:
04
02
2020
entrez:
25
2
2020
pubmed:
25
2
2020
medline:
22
5
2020
Statut:
epublish
Résumé
The placenta, a tissue that is metabolically active and rich in mitochondria, forms a critical interface between the mother and developing fetus. Oxidative stress within this tissue, derived from the dysregulation of reactive oxygen species (ROS), has been linked to a number of adverse fetal outcomes. While such outcomes have been associated with mitochondrial dysfunction, the causal role of mitochondrial dysfunction and mitochondrially generated ROS in altering the process of placentation remains unclear. In this study, mitochondrial complex I activity was attenuated using 10 nM rotenone to induce cellular oxidative stress by increasing mitochondrial ROS production in the BeWo choriocarcinoma cell line. Increased mitochondrial ROS resulted in a significant decrease in the transcripts which encode for proteins associated with fusion (GCM1, ERVW-1, and ERVFRD-1) resulting in a 5-fold decrease in the percentage of BeWo fusion. This outcome was associated with increased indicators of mitochondrial fragmentation, as determined by decreased expression of MFN2 and OPA1 along with an increase in a marker of mitochondrial fission (DRP1). Importantly, increased mitochondrial ROS also resulted in a 5.0-fold reduction of human placental lactogen (PL) and a 4.4-fold reduction of insulin like growth factor 2 (IGF2) transcripts; hormones which play an important role in regulating fetal growth. The pre-treatment of rotenone-exposed cells with 5 mM N-acetyl cysteine (NAC) resulted in the prevention of these ROS mediated changes in BeWo function and supports a central role for mitochondrial ROS signaling in the maintenance and function of the materno-fetal interface.
Identifiants
pubmed: 32092105
doi: 10.1371/journal.pone.0229332
pii: PONE-D-19-12972
pmc: PMC7039444
doi:
Substances chimiques
Placental Hormones
0
Reactive Oxygen Species
0
Rotenone
03L9OT429T
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0229332Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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