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Title: The control and manipulation of angiogenesis in the primate corpus luteum
Author: Dickson, Sarah
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2001
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In the marmoset luteal angiogenesis was manipulated by the administration of various putative angiogenesis inhibitors specifically targeting early luteal intense angiogenesis and mid-luteal ongoing angiogenesis. Luteal function was assessed by measuring plasma progesterone. Firstly, the effects of the angiogenesis inhibitor, TNP-470, shown to inhibit pregnancy in the mouse, were examined. This failed to affect endothelial cell proliferation or development of the microvasculature, which was confirmed by normal plasma progesterone concentrations, emphasising the need for caution in extrapolating results from the rodent. Secondly, in two studies marmosets were treated with a GnRH antagonist to analyse the control of luteal angiogenesis by the major luteotropic factor, LH in the early and mid-luteal phases. Withdrawal of LH had a devastating effect on the high level of endothelial cell proliferation in the early luteal phase but did not disturb the ongoing mid-luteal phase angiogenesis. Lutein cell morphology was severely disrupted after treatment at both stages, preventing the production and secretion of progesterone. Finally VEGF was immunoneutralised in three separate regimes of treatment in the early, from early to mid-, and specifically in the mid-luteal phase. Treatment suppressed proliferation in the early lateral phase and subsequently prevented formation of the mid-luteal microvascular network. The ongoing angiogenesis of the mid-CL was shown to be VEGF dependent, and VEGF withdrawal affected pericyte recruitment at all stages. To explore the endogenous control of luteal angiogenesis, expression of the angioproteins and their receptor, Tie 2 were analysed in association with expression of VEGF and its receptors in the human, using quantitative RT-PCR. The early luteal phase was associated with peak expression of all factors with slight increases in mRNAs for Ang-2 in the late CL and VEGF in the rescued. Since physiological angiogenesis occurs exclusively in reproductive tissues in the healthy adult, manipulation of angiogenesis may have important clinical implications in the treatment of infertility, in which angiogenesis is lacking, or for the development of anew approach to post-ovulatory fertility control based upon suppression of angiogenesis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available