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Endometrial stromal cells of women with recurrent miscarriage fail to discriminate between high- and low-quality human embryos

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Weimar, Charlotte H. E., Kavelaars, Annemieke, Brosens, Jan J., Gellersen, Birgit, de Vreeden-Elbertse, Johanna M. T., Heijnen, Cobi J. and Macklon, Nick S.. (2012) Endometrial stromal cells of women with recurrent miscarriage fail to discriminate between high- and low-quality human embryos. PLoS ONE, Vol.7 (No.7). e41424. ISSN 1932-6203

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Abstract

Background
The aetiology of recurrent miscarriage (RM) remains largely unexplained. Women with RM have a shorter time to pregnancy interval than normally fertile women, which may be due to more frequent implantation of non-viable embryos. We hypothesized that human endometrial stromal cells (H-EnSCs) of women with RM discriminate less effectively between high-and low-quality human embryos and migrate more readily towards trophoblast spheroids than H-EnSCs of normally fertile women.

Methodology/Principal Findings
Monolayers of decidualized H-EnSCs were generated from endometrial biopsies of 6 women with RM and 6 fertile controls. Cell-free migration zones were created and the effect of the presence of a high-quality (day 5 blastocyst, n = 13), a low-quality (day 5 blastocyst with three pronuclei or underdeveloped embryo, n = 12) or AC-1M88 trophoblast cell line spheroid on H-ESC migratory activity was analyzed after 18 hours. In the absence of a spheroid or embryo, migration of H-EnSCs from fertile or RM women was similar. In the presence of a low-quality embryo in the zone, the migration of H-EnSCs of control women was inhibited compared to the basal migration in the absence of an embryo (P<0.05) and compared to the migration in the presence of high-quality embryo (p<0.01). Interestingly, the migratory response H-EnSCs of women with RM did not differ between high- and low-quality embryos. Furthermore, in the presence of a spheroid their migration was enhanced compared to the H-EnSCs of controls (p<0.001).

Conclusions
H-EnSCs of fertile women discriminate between high- and low-quality embryos whereas H-EnSCs of women with RM fail to do so. H-EnSCs of RM women have a higher migratory response to trophoblast spheroids. Future studies will focus on the mechanisms by which low-quality embryos inhibit the migration of H-EnSCs and how this is deregulated in women with RM.

Item Type: Journal Article
Subjects: Q Science > QP Physiology
R Medicine > RG Gynecology and obstetrics
Divisions: Faculty of Medicine > Warwick Medical School > Reproductive Health
Library of Congress Subject Headings (LCSH): Miscarriage, Endometrium -- Physiology
Journal or Publication Title: PLoS ONE
Publisher: PLOS
ISSN: 1932-6203
Official Date: 2012
Volume: Vol.7
Number: No.7
Page Range: e41424
Identification Number: 10.1371/journal.pone.0041424
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
Funder: De Drie Lichten (Netherlands)
Grant number: 38/10 (DL)
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URI: http://wrap.warwick.ac.uk/id/eprint/49234

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