Title | Endothelial deletion of ADAM10, a key regulator of Notch signaling, causes impaired decidualization and reduced fertility in female mice. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Guahmich NLustgarten, Farber G, Shafiei S, McNally D, Redmond D, Kallinos E, Stuhlmann H, Dufort D, James D, Blobel CP |
Journal | Angiogenesis |
Volume | 23 |
Issue | 3 |
Pagination | 443-458 |
Date Published | 2020 Aug |
ISSN | 1573-7209 |
Keywords | ADAM10 Protein, Amyloid Precursor Protein Secretases, Animals, Decidua, Female, Fertility, Gene Deletion, Membrane Proteins, Mice, Mice, Knockout, Pregnancy, Receptors, Notch, Signal Transduction |
Abstract | <p>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.</p> |
DOI | 10.1007/s10456-020-09723-z |
Alternate Journal | Angiogenesis |
PubMed ID | 32385775 |
PubMed Central ID | PMC8603441 |
Grant List | R01 GM064750 / GM / NIGMS NIH HHS / United States P50 HD028934 / HD / NICHD NIH HHS / United States P50-HD28934 / / Eunice Kennedy Shriver National Institute of Child Health and Human Development / International R35 GM134907 / GM / NIGMS NIH HHS / United States R01 HL082098 / HL / NHLBI NIH HHS / United States |