کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2789047 1154466 2014 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inhibition of Delta-like 4 mediated signaling induces abortion in mice due to deregulation of decidual angiogenesis
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی تکاملی
پیش نمایش صفحه اول مقاله
Inhibition of Delta-like 4 mediated signaling induces abortion in mice due to deregulation of decidual angiogenesis
چکیده انگلیسی

ObjectiveTo explore whether the Dll4/Notch1 pathway plays a key role in regulating the vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) driven decidual angiogenesis and related pregnancy through induction of a tip/stalk phenotype.MethodsProgesterone-replaced ovariectomized pregnant mice received a single injection of YW152F (Dll4 blocking antibody, BAb) or placebo at embryonic day (E) 4.5. Animals were sacrificed at different time points; blood and uterus were collected for further analysis. Number of embryos and implantation site, uteri weight, and serum progesterone levels were assessed. Alterations in the tip/stalk phenotype were determined by quantitative immunofluorescent analysis of vascularization, Dll4 expression, cellular proliferation and apoptosis in uterine sections.ResultsAbrogation of Dll4 signaling leads to a promiscuous expression of Dll4, increased cell proliferation, apoptosis and vascularization at E 6.5. Such an abrogation was associated with a dramatic disruption of embryo growth and development starting at E 9.5.DiscussionThe observed promiscuous expression of Dll4 and the increase in cell proliferation, apoptosis and vascularization are events compatible with loss of the tip/stalk phenotype. Excessive (although very likely defective) decidual angiogenesis due to such vascular alterations is the most likely cause of subsequent interruption of embryo development and related pregnancy in Dll4 treated mice.ConclusionsDll4 plays a key role in regulating decidual angiogenesis and related pregnancy through induction of a tip/stalk phenotype.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Placenta - Volume 35, Issue 7, July 2014, Pages 501–508
نویسندگان
, , , , , ,