Cytochrome c oxidase IV isoform 1 (COX4-1) regulates the proliferation, migration and invasion of trophoblast cells via modulating mitochondrial function.
Placenta
; 151: 48-58, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38718733
ABSTRACT
INTRODUCTION:
Spontaneous miscarriage is a common complication of early pregnancy. Previous studies have shown that mitochondrial function plays an important role in establishment of a successful pregnancy. Cytochrome c oxidase subunit 4 isoform 1 (COX4I1), a component of electron transport chain complex â £, is required for coupling the rate of ATP production to energetic requirements. However, there is very limited research on its role in trophoblast biology and how its dysfunction may contribute to spontaneous miscarriage.METHODS:
Placental villi (7-10 weeks gestational age) collected from either induced termination of pregnancy or after spontaneous miscarriage were examined for expression of COX4I1. COX4I1 was knocked down by siRNA transfection of primary isolates of EVT cells. Real-time cell analysis (RTCA) and 5-Ethynyl-2'-deoxyuridine (EdU) were used to detect changes in proliferation ability after COX4I1 knockdown of EVT cells. Migration and invasion indices were determined by RTCA. Mitochondrial morphology was observed via MitoTracker staining. Oxidative phosphorylation, ATP production, and glycolysis in COX4I1-deficient cells and controls were assessed by a cellular energy metabolism analyzer (Seahorse).RESULTS:
In placental villous tissue, COX4I1 expression was significantly decreased in the spontaneous miscarriage group. Knockdown of COX4I1 inhibited EVT cell proliferation, increased the migration and invasion ability and mitochondrial fusion of EVT cells. Mitochondrial respiration and glycolysis were impaired in COX4I1-deficient EVT cells. Knockdown of MMP1 could rescue the increased migration and invasion induced by COX4I1 silencing.DISCUSSION:
Low expression of COX4I1 leads to mitochondrial dysfunction in EVT, resulting in altered trophoblast function, and ultimately to pregnancy loss.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Trofoblastos
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Aborto Espontâneo
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Movimento Celular
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Complexo IV da Cadeia de Transporte de Elétrons
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Proliferação de Células
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Mitocôndrias
Limite:
Female
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Humans
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Pregnancy
Idioma:
En
Revista:
Placenta
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China