期刊
ANGIOGENESIS
卷 23, 期 3, 页码 443-458出版社
SPRINGER
DOI: 10.1007/s10456-020-09723-z
关键词
Endothelial cells; ADAM10 (a disintegrin and metalloprotease 10); Notch; Endometrial vasculature; Infertility
资金
- NIH [R01 HL082098, R01 GM64750, R35 GM134907]
- March of Dimes Research Foundation [6-FY14-411]
- American Heart Association Predoctoral Fellowship [17PRE33380001]
- Eunice Kennedy Shriver NICHD/NIH (NCTRI) [P50-HD28934]
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 A10 Delta EC 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 A10 Delta EC 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.
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