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

Endometrial stromal cells of women with recurrent miscarriage fail to discriminate between high- and low-quality human embryos
Endometrial stromal cells of women with recurrent miscarriage fail to discriminate between high- and low-quality human embryos
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.
1932-6203
e41424-[8pp]
Weimar, Charlotte H.E.
d79fad64-abe7-403c-addd-661df3dfea3b
Kavelaars, Annemieke
ab4a504e-74de-4c7b-86b4-acac8363cc77
Brosens, Jan J.
0644527d-213a-44f8-9557-0588eaaac2c9
Gellersen, Birgit
80858181-55c7-43d8-87ed-6b8b7fdb162f
de Vreeden-Elbertse, Johanna M.T.
7e826288-b708-4bc7-a08b-f21141b62e3a
Heijnen, Cobi J.
7327b3c6-a13d-4569-8a8a-f16dec3d9292
Macklon, Nick S.
7db1f4fc-a9f6-431f-a1f2-297bb8c9fb7e
Weimar, Charlotte H.E.
d79fad64-abe7-403c-addd-661df3dfea3b
Kavelaars, Annemieke
ab4a504e-74de-4c7b-86b4-acac8363cc77
Brosens, Jan J.
0644527d-213a-44f8-9557-0588eaaac2c9
Gellersen, Birgit
80858181-55c7-43d8-87ed-6b8b7fdb162f
de Vreeden-Elbertse, Johanna M.T.
7e826288-b708-4bc7-a08b-f21141b62e3a
Heijnen, Cobi J.
7327b3c6-a13d-4569-8a8a-f16dec3d9292
Macklon, Nick S.
7db1f4fc-a9f6-431f-a1f2-297bb8c9fb7e

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, 7 (7), e41424-[8pp]. (doi:10.1371/journal.pone.0041424). (PMID:22848492)

Record type: Article

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.

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Published date: 25 July 2012
Organisations: Human Development & Health

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Local EPrints ID: 346455
URI: http://eprints.soton.ac.uk/id/eprint/346455
ISSN: 1932-6203
PURE UUID: 3fbfb1a0-825e-4a80-96b8-f1e9b05d3866

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Date deposited: 15 Jan 2013 14:53
Last modified: 14 Mar 2024 12:36

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Contributors

Author: Charlotte H.E. Weimar
Author: Annemieke Kavelaars
Author: Jan J. Brosens
Author: Birgit Gellersen
Author: Johanna M.T. de Vreeden-Elbertse
Author: Cobi J. Heijnen
Author: Nick S. Macklon

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