Molecular pathways of senescence regulate placental structure and function.
EMBO J
; 38(18): e100849, 2019 09 16.
Article
em En
| MEDLINE
| ID: mdl-31424120
ABSTRACT
The placenta is an autonomous organ that maintains fetal growth and development. Its multinucleated syncytiotrophoblast layer, providing fetal nourishment during gestation, exhibits characteristics of cellular senescence. We show that in human placentas from pregnancies with intrauterine growth restriction, these characteristics are decreased. To elucidate the functions of pathways regulating senescence in syncytiotrophoblast, we used dynamic contrast-enhanced MRI in mice with attenuated senescence programs. This approach revealed an altered dynamics in placentas of p53-/- , Cdkn2a-/- , and Cdkn2a-/- ;p53-/- mice, accompanied by histopathological changes in placental labyrinths. Human primary syncytiotrophoblast upregulated senescence markers and molecular pathways associated with cell-cycle inhibition and senescence-associated secretory phenotype. The pathways and components of the secretory phenotype were compromised in mouse placentas with attenuated senescence and in human placentas from pregnancies with intrauterine growth restriction. We propose that molecular mediators of senescence regulate placental structure and function, through both cell-autonomous and non-autonomous mechanisms.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Placenta
/
Proteína Supressora de Tumor p53
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Inibidor p16 de Quinase Dependente de Ciclina
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Redes Reguladoras de Genes
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Retardo do Crescimento Fetal
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Pregnancy
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Israel