Endothelial deletion of ADAM10, a key regulator of Notch signaling, causes impaired decidualization and reduced fertility in female mice.
ADAM10 (a disintegrin and metalloprotease 10)
Endometrial vasculature
Endothelial cells
Infertility
Notch
Journal
Angiogenesis
ISSN: 1573-7209
Titre abrégé: Angiogenesis
Pays: Germany
ID NLM: 9814575
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
02
12
2019
accepted:
23
04
2020
pubmed:
10
5
2020
medline:
7
7
2021
entrez:
10
5
2020
Statut:
ppublish
Résumé
During the initiation of pregnancy, the vasculature of the implantation site expands rapidly, yet little is known about this process or its role in fertility. Here, we report that endothelial-specific deletion of a disintegrin and metalloprotease 10 (ADAM10), an essential regulator of Notch signaling, results in severe subfertility in mice. We found that implantation sites develop until 5.5 days post conception (dpc) but are resorbed by 6.5 dpc in A10ΔEC mice. Analysis of the mutant implantation sites showed impaired decidualization and abnormal vascular patterning compared to controls. Moreover, RNA-seq analysis revealed changes in endothelial cell marker expression consistent with defective ADAM10/Notch signaling in samples from A10ΔEC mice, suggesting that this signaling pathways is essential for the physiological function of endometrial endothelial cells during early pregnancy. Our findings raise the possibility that impaired endothelial cell function could be a cause for repeated pregnancy loss (RPL) and infertility in humans.
Identifiants
pubmed: 32385775
doi: 10.1007/s10456-020-09723-z
pii: 10.1007/s10456-020-09723-z
pmc: PMC8603441
mid: NIHMS1753889
doi:
Substances chimiques
Membrane Proteins
0
Receptors, Notch
0
Amyloid Precursor Protein Secretases
EC 3.4.-
ADAM10 Protein
EC 3.4.24.81
Adam10 protein, mouse
EC 3.4.24.81
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
443-458Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM064750
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD028934
Pays : United States
Organisme : Eunice Kennedy Shriver National Institute of Child Health and Human Development
ID : P50-HD28934
Pays : International
Organisme : NIGMS NIH HHS
ID : R35 GM134907
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL082098
Pays : United States
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