The Library

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

Tools

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

[img]
Preview
 Text
WRAP_Brosens_journal.pone.0041424.pdf - Published Version
Download (2237Kb) | Preview

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 > Translational & Systems Medicine > Reproductive Health
Faculty of Medicine > Warwick Medical School
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)
References:

1. Evers JL (2002) Female subfertility. Lancet 360: 151–159.
2. Macklon NS, Geraedts JP, Fauser BC (2002) Conception to ongoing pregnancy:
the ‘black box’ of early pregnancy loss. Hum Reprod Update 8: 333–343.
3. Teklenburg G, Salker M, Molokhia M, Lavery S, Trew G, et al. (2010) Natural
selection of human embryos: decidualizing endometrial stromal cells serve as
sensors of embryo quality upon implantation. PLoS One 5: e10258.
4. Vanneste E, Voet T, Le CC, Ampe M, Konings P, et al. (2009) Chromosome
instability is common in human cleavage-stage embryos. Nat Med 15: 577–583.
5. Rai R, Regan L (2006) Recurrent miscarriage. Lancet 368: 601–611.
6. Stirrat GM (1990) Recurrent miscarriage. Lancet 336: 673–675.
7. Aplin JD, Hey NA, Li TC (1996) MUC1 as a cell surface and secretory
component of endometrial epithelium: reduced levels in recurrent miscarriage.
Am J Reprod Immunol 35: 261–266.
8. Quenby S, Vince G, Farquharson R, Aplin J (2002) Recurrent miscarriage: a
defect in nature’s quality control? Hum Reprod 17: 1959–1963.
9. Salker M, Teklenburg G, Molokhia M, Lavery S, Trew G, et al. (2010) Natural
selection of human embryos: impaired decidualization of endometrium disables
embryo-maternal interactions and causes recurrent pregnancy loss. PLoS One 5:
e10287.
10. Teklenburg G, Salker M, Heijnen C, Macklon NS, Brosens JJ (2010) The
molecular basis of recurrent pregnancy loss: impaired natural embryo selection.
Mol Hum Reprod 16: 886–895.
11. Wilcox AJ, Baird DD, Weinberg CR (1999) Time of implantation of the
conceptus and loss of pregnancy. N Engl J Med 340: 1796–1799.
12. Grewal S, Carver JG, Ridley AJ, Mardon HJ (2008) Implantation of the human
embryo requires Rac1-dependent endometrial stromal cell migration. Proc Natl
Acad Sci U S A 105: 16189–16194.
13. Grewal S, Carver J, Ridley AJ, Mardon HJ (2010) Human endometrial stromal
cell rho GTPases have opposing roles in regulating focal adhesion turnover and
embryo invasion in vitro. Biol Reprod 83: 75–82.
14. Gellersen B, Reimann K, Samalecos A, Aupers S, Bamberger AM (2010)
Invasiveness of human endometrial stromal cells is promoted by decidualization
and by trophoblast-derived signals. Hum Reprod 25: 862–873.
15. Gonzalez M, Neufeld J, Reimann K, Wittmann S, Samalecos A, et al. (2011)
Expansion of human trophoblastic spheroids is promoted by decidualized
endometrial stromal cells and enhanced by heparin-binding epidermal growth
factor-like growth factor and interleukin-1 beta. Mol Hum Reprod 17: 421–433.
16. Bielanska M, Tan SL, Ao A (2002) Chromosomal mosaicism throughout human
preimplantation development in vitro: incidence, type, and relevance to embryo
outcome. Hum Reprod 17: 413–419.
17. Mansouri-Attia N, Sandra O, Aubert J, Degrelle S, Everts RE, et al. (2009)
Endometrium as an early sensor of in vitro embryo manipulation technologies.
Proc Natl Acad Sci U S A 106: 5687–5692.
18. Carp H, Toder V, Aviram A, Daniely M, Mashiach S, et al. (2001) Karyotype of
the abortus in recurrent miscarriage. Fertil Steril 75: 678–682.
19. Lakovschek IC, Streubel B, Ulm B. (2011) Natural outcome of trisomy 13,
trisomy 18, and triploidy after prenatal diagnosis. Am J Med Genet A 155:
2626–2633.
20. Leese HJ, Sturmey RG, Baumann CG, McEvoy TG (2007) Embryo viability
and metabolism: obeying the quiet rules. Hum Reprod 22: 3047–3050.
21. Leese HJ, Baumann CG, Brison DR, McEvoy TG, Sturmey RG (2008)
Metabolism of the viable mammalian embryo: quietness revisited. Mol Hum
Reprod 14: 667–672.
22. Stokes PJ, Hawkhead JA, Fawthrop RK, Picton HM, Sharma V, et al. (2007)
Metabolism of human embryos following cryopreservation: implications for the safety and selection of embryos for transfer in clinical IVF. Hum Reprod 22:
829–835.
23. Picton HM, Elder K, Houghton FD, Hawkhead JA, Rutherford AJ, et al. (2010)
Association between amino acid turnover and chromosome aneuploidy during
human preimplantation embryo development in vitro. Mol Hum Reprod 16:
557–569.
24. Redman CW, Sargent IL (2008) Circulating microparticles in normal pregnancy
and pre-eclampsia. Placenta 29 Suppl A: S73–S77.
25. Popovici RM, Betzler NK, Krause MS, Luo M, Jauckus J, et al. (2006) Gene
expression profiling of human endometrial-trophoblast interaction in a coculture
model. Endocrinology 147: 5662–5675.
26. Baart EB, Martini E, van den Berg I, Macklon NS, Galjaard RJ, et al. (2006)
Preimplantation genetic screening reveals a high incidence of aneuploidy and
mosaicism in embryos from young women undergoing IVF. Hum Reprod 21:
223–233.
27. Musters AM, Repping S, Korevaar JC, Mastenbroek S, Limpens J, et al. (2011)
Pregnancy outcome after preimplantation genetic screening or natural
conception in couples with unexplained recurrent miscarriage: a systematic
review of the best available evidence. Fertil Steril 95: 2153–2157.
28. Gardner DK, Lane M, Stevens J, Schlenker T, Schoolcraft WB (2000) Blastocyst
score affects implantation and pregnancy outcome: towards a single blastocyst
transfer. Fertil Steril 73: 1155–1158.
URI: http://wrap.warwick.ac.uk/id/eprint/49234

Request changes or add full text files to a record

Actions (login required)

View Item View Item

Document Downloads

More statistics for this item...