期刊
EMBO JOURNAL
卷 38, 期 18, 页码 -出版社
WILEY
DOI: 10.15252/embj.2018100849
关键词
gelatinase; intrauterine growth restriction; placenta; senescence; syncytiotrophoblast
资金
- European Research Council under the European Union's FP7 [309688]
- Israel Science Foundation [634-15]
- Seventh Framework European Research Council Advanced Grant [232640IMAGO]
- National Institutes of Health [1R01HD086323-01]
- European Research Council (ERC) [309688] Funding Source: European Research Council (ERC)
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.
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