Research Description

Angiogenesis is the physiological process that consists of the formation of new blood vessels from preexisting vessels.
The Angiogenesis has increased pathologically in numerous types of cancer, because the tumors find in the phenomenon an ideal solution to supply nutrients and oxygen that permit them to subsist and to be developed in situations of limited growth.
Numerous oncological therapies currently are infact based on the use of antiangiogenic agents beingthe main target of the growth factor of the vascular endothelial (VEGF) or their receptor 2 (VEGFR2).
Nevertheless, the angiogenesis in physiological conditions is not only desirable but indispensable for the embryonic development, growth of the organism and the healing of wounds. Also for more than a decade we know that the angiogenesis develops cyclically in ovary and uterus being indispensable for the formation and regeneration of the reproductive structures in processes such as ovulation and corpus luteum formation.
In fact we suspect that the deregulation of the angiogenesis in these organs can lead to dependent ovarian pathologies with the result of difficulties or impossibilities for women to conceive in an autonomous way Employing present human ovaries in the files of pathological anatomy has been verified that contrary to expectations are the older women and lower reproductive capacity the ones that greater vascularization have in their ovaries.
This phenomenon of apparent paradox as for the functionality of the biggest/smaller angiogenesis originally observed in tumor studies where they tried to determine the effect of the inhibition of system Notch of ligandos and receptors on tumor growth.
In such animals was observed that, paradoxically those animals which had inhibited the Notch system had much more vascularized tumors but that nevertheless they were in size a lot more small that the tumors of the animals in which had not inhibited the notch system.
In particular it seems that the VEGF system originally started the angiogenic process by promoting endothelial cell migration from preexistentes vessels to form new ones.. .
However, the activation of the notch is in charge of controlling initial angiogenesis initial, braking and channeling the proliferation as well as integrating and joining the endoteliales cells to assure the formation of those that contain a central lumen through which blood circulates. When the system Notch is not active the endothelial cells proliferate massively and without control and besides do not give place to vessels with lumen.
In absence of lumen the endothelial cells give rise to aberrant vessels that do not carry nutrients and that limit the growth of the tumors, explaining the apparently paradoxical phenomena described previously.

Our concrete objectives are centered in determining if:

• The system Notch is indispensable and plays a fundamental role in the physiological angiogenesis that occurs during the ovulation and formation of the corpus luteum in physiological conditions
• The blockade, lack of signposting or deregulation in the signposting of Notch leads to failures in the ovarian functionality mainly in the form of::    - Anovulation
     - Defects in the follicular ripening

Effect of the blockade of Notch on the vascularization and follicular structure.

Both images belong to stimulated mouse ovary sections for the ovulation and that have been by means of immunohistochemically technical to visualize PECAM (marker of endothelial) in brown A) Corresponds to section of animal control while B) corresponds to section of animal treated with gamma secretasa for the inhibition of Notch. Note the loss of endothelial continuity in the endotelial structure that surrounds B) and as is completely maintained continues in A).p>

Posted Items

• Delgado-Rosas F, Gaytán M, Morales C, Gómez R, Gaytán F.

  Superficial ovarian cortex vascularization is inversely related to the follicle reserve in normal cycling ovaries and is increased in polycystic ovary syndrome. Hum Reprod. 2009; 5:1142-51

• Gomez R, Jovanovic C, Sauer C, Sauer M, Kitajewski J, Zimmermann C.

  Notch1 signalling regulates sprouting angiogenesis in corpora lutea through tip cells and stalk cells" ESHRE meeting 2010. Abstract P110