Open AccessEndothelial deletion of ADAM10, a key regulator of Notch signaling, causes impaired decidualization and reduced fertility in female mice
Author(s) -
Nicole Lustgarten Guahmich,
Gregory Farber,
Shiva Shafiei,
Dylan McNally,
David Redmond,
Eleni Kallinos,
Heidi Stuhlmann,
Daniel Dufort,
Daylon James,
Carl P. Blobel
Publication year - 2020
Publication title -
angiogenesis (london)
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.061
H-Index - 88
eISSN - 1573-7209
pISSN - 0969-6970
DOI - 10.1007/s10456-020-09723-z
Subject(s) - decidualization , notch signaling pathway , angiogenesis , regulator , biology , adam10 , microbiology and biotechnology , endothelial stem cell , endocrinology , medicine , endometrium , signal transduction , andrology , disintegrin , cancer research , metalloproteinase , matrix metalloproteinase , genetics , gene , in vitro
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.