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Localization of angiogenic growth factors and their receptors in the human endometrium throughout the menstrual cycle and in recurrent miscarriage

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Lash, Gendie E., Innes, Barbara A., Drury, Josephine A., Robson, Samuel Charles, Quenby, Siobhan and Bulmer, Judith N. (2012) Localization of angiogenic growth factors and their receptors in the human endometrium throughout the menstrual cycle and in recurrent miscarriage. Human Reproduction, Volume 27 (Number 1). pp. 183-195. doi:10.1093/humrep/der376

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Official URL: http://dx.doi.org/10.1093/humrep/der376

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Abstract

BACKGROUND:
Angiogenesis is a key feature of endometrial development. Inappropriate endometrial vascular development has been associated with recurrent miscarriage (RM) with increased amounts of perivascular smooth muscle cells surrounding them.
METHODS:
In the current study, we have used immunohistochemistry to study temporal and spatial expression of a series of angiogenic growth factors (AGFs) and their receptors; vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF-D, VEGF-R1, VEGF-R2, VEGF-R3, platelet-derived growth factor (PDGF)-BB, PDGF-Rα, PDGF-Rβ, transforming growth factor (TGF)-β1, TGF-βRI, TGF-βRII, angiopoietin (Ang)-1, Ang-2 and Tie-2, in the proliferative, early secretory and mid-late secretory phase endometrium from control women as well as in the mid-late secretory phase of women with a history of RM. The AGFs and their receptors studied were immunostained and assessed separately in stromal, vascular smooth muscle, endothelial and glandular epithelial cells. Laser capture microdissection and real-time RT-PCR were used to confirm expression patterns observed by immunohistochemistry.
RESULTS:
Most AGFs investigated showed both temporal and spatial expression patterns in normal cycling endometrium. In addition, immunostaining intensity for several AGFs was altered in women with a history of RM, particularly in vascular smooth muscle cells (VSMCs). VSMC expression of TGF-β1, VEGF-R1 and VEGF-R2 was increased while expression of PDGF-BB, TGF-βRI, TGF-βRII, Ang-2, VEGF-A and VEGF-C was reduced.
CONCLUSIONS:
This study confirms that the cycling endometrium is a highly angiogenic tissue and that this process is likely to be altered in women with a history of RM and may contribute to the aetiology of this condition.

Item Type: Journal Article
Divisions: Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Reproductive Health ( - until July 2016)
Faculty of Medicine > Warwick Medical School
Journal or Publication Title: Human Reproduction
Publisher: OUP
ISSN: 0268-1161
Official Date: January 2012
Dates:
DateEvent
January 2012Published
10 October 2011Accepted
Volume: Volume 27
Number: Number 1
Page Range: pp. 183-195
DOI: 10.1093/humrep/der376
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access

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