title: Endometrial stromal cells of women with recurrent miscarriage fail to discriminate between high- and low-quality human embryos.
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.
  
  
  RESULTS
  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.
authors: Laboratory of Neuroimmunology and Developmental Origins of Disease (NIDOD), University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Charlotte H E
authors: CH
authors: Weimar
authors: Annemieke
authors: A
authors: Kavelaars
authors: Jan J
authors: JJ
authors: Brosens
authors: Birgit
authors: B
authors: Gellersen
authors: Johanna M T
authors: JM
authors: de Vreeden-Elbertse
authors: Cobi J
authors: CJ
authors: Heijnen
authors: Nick S
authors: NS
authors: Macklon
mesh_terms: D000026:Abortion, Habitual / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000328:Adult; D002465:Cell Movement; D002478:Cells, Cultured; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D011247:Pregnancy; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D014327:Trophoblasts / Q000378:metabolism* / Q000473:pathology