Unique patterns of Notch1, Notch4 and Jagged1 expression in ovarian vessels during folliculogenesis and corpus luteum formation

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Abstract

Notch signaling functions to regulate cell-fate decisions by modulating differentiation, proliferation, and survival of cells. Notch receptors and ligands are expressed in embryonic vasculature and are required for the remodeling of the primary embryonic vasculature of mice. Here, we characterize the expression patterns of Notch1, Notch4, and Jagged1 proteins during the process of folliculogenesis and corpus luteum formation in the mouse ovary, an organ with dynamic physiological angiogenic growth. These Notch proteins and ligand are expressed in a subset of ovarian vessels, including both mature ovarian vasculature as well as angiogenic neovessels. Their expression in the ovary was found in both endothelial and vascular associated mural cells. Our data suggest a complex regulatory role for the Notch signaling pathway during mouse oogenesis and ovarian neovascularization.

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Results and discussion

The Notch signaling pathway regulates cell-fate determination and patterning of the vascular system. There are four Notch receptors (Notch1-4) and two families of ligands (Jagged1,2 and Delta-like (Dll) 1,3,4), which are also transmembrane proteins. The Notch signaling pathway is initiated by the interaction between extracellular domains of Notch receptors and their ligands on the surface of adjacent cells (Shawber and Kitajewski, 2004, Weinmaster, 1997). Studies have shown that Notch signaling

Animals and hormone treatment

CD-1 female mice (Charles River Company) were used for all studies. Hypophysectomy was performed on immature, 21–23 day old, female CD1 mice by Charles River Laboratories (Baltimore, MD) using a transpharyngeal approach. Due to the timing of the surgery, which is performed prepubertally, only immature follicles are present in the ovary upon receipt. Four groups of animals (three per group) were analyzed.

Acknowledgements

We would like to thank Dr Gary Nakhuda for helpful discussions. We acknowledge Kiran Manga and Sam Pauli for technical assistance and Victor Vorontchikhin for assistance with figures. This work was supported by NIH RO1 HL538530 (JK), postdoctoral fellowship DOD DAMD17-031-0218 (CS) and training grant NIH 5T32 DK07328 (MV).

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