Unravelling the impact of intrauterine growth restriction on heart development: insights into mitochondria and sexual dimorphism from a non-hominoid primate.
Clin Sci (Lond)
; 135(14): 1767-1772, 2021 07 30.
Article
em En
| MEDLINE
| ID: mdl-34313297
ABSTRACT
Fetal exposure to an unfavorable intrauterine environment programs an individual to have a greater susceptibility later in life to non-communicable diseases, such as coronary heart disease, but the molecular processes are poorly understood. An article in Clinical Science recently reported novel details on the effects of maternal nutrient reduction (MNR) on fetal heart development using a primate model that is about 94% genetically similar to humans and is also mostly monotocous. MNR adversely impacted fetal left ventricular (LV) mitochondria in a sex-dependent fashion with a greater effect on male fetuses, although mitochondrial transcripts increased more so in females. Increased expression for several respiratory chain and adenosine triphosphate (ATP) synthase proteins were observed. However, fetal LV mitochondrial complex I and complex II/III activities were significantly decreased, likely contributing to a 73% decreased LV ATP content and increased LV lipid peroxidation. Moreover, MNR fetal LV mitochondria showed sparse and disarranged cristae. This study indicates that mitochondria are targets of the remodeling and imprinting processes in a sex-dependent manner. Mitochondrial ROS production and inadequate energy production add another layer of complexity. Altogether these observations raise the possibility that dysfunctional mitochondria in the fetus may contribute in turn to epigenetic memory of in utero stress in the adult. The role of mitoepigenetics and involvement of mitochondrial and genomic non-coding RNAs in mitochondrial functions and nuclei-mitochondria crosstalk with in utero stress awaits further investigation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Caracteres Sexuais
/
Retardo do Crescimento Fetal
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Coração
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Mitocôndrias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Clin Sci (Lond)
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos