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Hum. Reprod. Advance Access originally published online on September 4, 2008
Human Reproduction 2008 23(12):2782-2790; doi:10.1093/humrep/den298
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© The Author 2008. 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
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Estrogen receptor related beta is expressed in human endometrium throughout the normal menstrual cycle

Vincent Bombail1, Sheila MacPherson1, Hilary O.D. Critchley2 and Philippa T.K. Saunders1,3

1 MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK 2 Division of Reproductive and Developmental Sciences, University of Edinburgh, The Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK

3 Correspondence address. Tel: +44-131-242-6388; E-mail: p.saunders{at}ed.ac.uk or p.saunders{at}hrsu.mrc.ac.uk

BACKGROUND: Estrogen receptor related beta (ERRβ, ESRRB/NR3B2) is an orphan receptor that shares significant sequence homology with estrogen receptors ER{alpha} and ERβ. ERR family members are reported to exhibit constitutive transcriptional activity; however, little is known about the biological function of ERRβ. In an attempt to delineate its role, we examined expression of ERRβ in normal human endometrium, a tissue that undergoes cyclic remodelling under the influence of estrogen and progesterone.

METHODS: Well-characterized endometrial tissue (n = 31), including full-thickness biopsies, was obtained from women with regular menstrual cycles. RT–PCR was used to measure mRNA encoding ERRβ, the peroxisome proliferator activated receptor gamma coactivators (PGC)-1{alpha} and β and to determine whether ERRβ splice variant mRNAs were expressed. ERRβ was immunolocalized using both single and double antibody immunohistochemistry.

RESULTS: Total ERRβ mRNA appeared higher in proliferative phase samples but results did not reach significance. Transcripts corresponding to the long- and short-splice variants of ERRβ as well as PGC1{alpha} and β were detected but ERRβ{Delta}10 was absent. ERRβ protein was localized to cell nuclei within multiple endometrial cell types including the glands, stroma, endothelium and immune cells, including uterine natural killer (uNK) cells and macrophages. Fluorescent immunohistochemistry revealed that some cells co-expressed ERRβ and ER{alpha} or ERβ, for example, endothelial and uNK cells were ERRβ+/ERβ+.

CONCLUSIONS: ERRβ mRNA and protein are expressed in healthy human endometrium. Further studies are warranted to characterize the functional impact of ERRβ on endometrial biology.

Key words: endometrium/estrogen receptor/uterine natural killer cell/macrophage/peroxisome proliferator-activated receptor gamma coactivator

Submitted on March 5, 2008; resubmitted on June 10, 2008; accepted on July 10, 2008.


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