pt9b00050_si_001.pdf (571.82 kB)
Inhibition of Jagged-Specific Notch Activation Reduces Luteal Angiogenesis and Causes Luteal Hemorrhaging of Hormonally Stimulated Ovaries
journal contribution
posted on 2019-09-09, 16:38 authored by Natalie Kofler, L. A. Naiche, Lilli D. Zimmerman, Jan K. KitajewskiRobust
angiogenesis in the corpus luteum is critical for maintenance
of pregnancy and thus mammalian female fertility. During angiogenesis,
blood vessels sprout from pre-existing vasculature and recruit pericytes
to induce maturation and vessel quiescence. Pericytes are associated
with capillaries and regulate endothelial cell proliferation, vessel
diameter, and vascular permeability. Endothelial induction of Notch
signaling in adjacent pericytes helps recruit and maintain pericyte
coverage in some but not all tissue types. We have employed a Notch
decoy, N110–24, which blocks Notch signaling in
a ligand-specific manner, and determined that pharmacological inhibition
of Notch ligand Jagged blocks luteal angiogenesis after normal ovulation,
resulting in reduced luteal vasculature. Conversely, after ovarian
hyperstimulation, a condition which occurs during fertility treatments,
Jagged inhibition causes vascular dilation and hemorrhage. These results
indicate that Jagged inhibition has effects in different ovarian angiogenic
conditions, promoting vascular growth in the corpus luteum and vascular
stability in hyperstimulated ovaries.