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

Lookup NU author(s): Dr Gendie Lash, Barbara Innes, Dr John Drury, Professor Steve RobsonORCiD, Dr Judith Bulmer

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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-R alpha, PDGF-R beta, transforming growth factor (TGF)-beta 1, TGF-beta RI, TGF-beta RII, 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-beta 1, VEGF-R1 and VEGF-R2 was increased while expression of PDGF-BB, TGF-beta RI, TGF-beta RII, 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.

Publication metadata

Author(s): Lash GE, Innes BA, Drury JA, Robson SC, Quenby S, Bulmer JN

Publication type: Article

Publication status: Published

Journal: Human Reproduction

Year: 2012

Volume: 27

Issue: 1

Pages: 183-195

Print publication date: 10/11/2011

ISSN (print): 0268-1161

ISSN (electronic): 1460-2350

Publisher: Oxford University Press

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

DOI: 10.1093/humrep/der376

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