Advanced maternal age causes premature placental senescence and malformation via dysregulated α-Klotho expression in trophoblasts.
advanced maternal age
placenta
senescence
trophoblast
α-klotho
Journal
Aging cell
ISSN: 1474-9726
Titre abrégé: Aging Cell
Pays: England
ID NLM: 101130839
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
revised:
20
05
2021
received:
11
11
2020
accepted:
24
05
2021
pubmed:
10
6
2021
medline:
3
2
2022
entrez:
9
6
2021
Statut:
ppublish
Résumé
Advanced maternal age (AMA) pregnancy is associated with higher risks of adverse perinatal outcomes, which may result from premature senescence of the placenta. α-Klotho is a well-known antiaging protein; however, its expression and effect on the placenta in AMA pregnancies have not yet been fully elucidated. The expression patterns of α-Klotho in mouse and human placentas from AMA pregnancies were determined by Western blotting and immunohistochemistry (IHC) staining. α-Klotho expression in JAR cells was manipulated to investigate its role in trophoblastic senescence, and transwell assays were performed to assess trophoblast invasion. The downstream genes regulated by α-Klotho in JAR cells were first screened by mRNA sequencing in α-Klotho-knockdown and control JAR cells and then validated. α-Klotho-deficient mice were generated by injecting klotho-interfering adenovirus (Ad-Klotho) via the tail vein on GD8.5. Ablation of α-Klotho resulted in not only a senescent phenotype and loss of invasiveness in JAR cells but also a reduction in the transcription of cell adhesion molecule (CAM) genes. Overexpression of α-Klotho significantly improved invasion but did not alter the expression of senescence biomarkers. α-Klotho-deficient mice exhibited placental malformation and, consequently, lower placental and fetal weights. In conclusion, AMA results in reduced α-Klotho expression in placental trophoblasts, therefore leading to premature senescence and loss of invasion (possibly through the downregulation of CAMs), both of which ultimately result in placental malformation and adverse perinatal outcomes.
Identifiants
pubmed: 34105233
doi: 10.1111/acel.13417
pmc: PMC8282245
doi:
Substances chimiques
Klotho Proteins
EC 3.2.1.31
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13417Informations de copyright
© 2021 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
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