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Mol. Hum. Reprod. Advance Access originally published online on September 5, 2007
Molecular Human Reproduction 2007 13(10):729-736; doi:10.1093/molehr/gam056
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Effects of inhibition of vascular endothelial growth factor at time of selection on follicular angiogenesis, expansion, development and atresia in the marmoset

P.D. Taylor1, H. Wilson1, S.G. Hillier2, S.J. Wiegand3 and H.M. Fraser1,4

1Medical Research Council Human Reproductive Sciences Unit, Centre for Reproductive Biology, University of Edinburgh, The Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK 2Division of Reproductive and Developmental Sciences, Centre for Reproductive Biology, University of Edinburgh, The Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK 3 Regeneron Pharmaceuticals, Tarrytown, NY 10591, USA

4Correspondence address. Tel: 0131-242-6222; Fax: 0131-242-6231; E-mail: h.fraser{at}hrsu.mrc.ac.uk

This study determined the effects of inhibiting vascular endothelial growth factor (VEGF) at follicle selection. Marmosets were given an injection of VEGF antagonist, the VEGF Trap on Day 5 of the follicular phase and ovaries were evaluated on Day 10 or 15. Ovaries from controls were assessed on Day 5 (time of selection), Day 10 (peri-ovulatory) and Day 15 (luteal phase). At Day 10, ovaries of four of the five controls contained dominant follicles, while one had ovulated. VEGF Trap-treated ovaries also contained large follicles on Day 10, but VEGF inhibition had suppressed endothelial cell proliferation, leading to reductions in the thecal vascularization and plasma estradiol relative to controls. By Day 15, ovaries of controls contained active corpora lutea whereas ovaries of four of the five treated animals still contained large antral follicles similar in size to pre-ovulatory follicles, and one had small, avascular corpora lutea. However, these follicles had a restricted vasculature, increased incidence of activated caspase-3 staining and morphological features indicating they would become degenerative non-functional cysts. These results show that after follicle selection, VEGF is essential for angiogenesis and the generation of healthy ovulatory follicles and corpora lutea, but fluid accumulation can still occur in selected follicles in the absence of VEGF.

Key words: ovary/angiogenesis/follicle/marmoset monkey/VEGF Trap

Submitted on June 4, 2007; resubmitted on July 17, 2007; accepted on July 18, 2007.


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