Impaired Function of Trophoblast Cells Derived from Translocated HESCs May Explain Pregnancy Loss in Women with Balanced Translocation (11;22)

Overview

Journal J Assist Reprod Genet

Publisher Springer

Specialties Genetics
Reproductive Medicine

Date 2016 Aug 10

PMID 27503403

Citations 2

Authors

Alina Shpiz

Dalit Ben-Yosef

Yael Kalma

Affiliations

Soon will be listed here.

Abstract

Purpose: The aim of the study was to study whether the trophoblasts carrying unbalanced translocation 11,22 [t(11;12)] display abnormal expression of trophoblastic genes and impaired functional properties that may explain implantation failure.

Methods: t(11;22) hESCs and control hESCs were differentiated in vitro into trophoblast cells in the presence of BMP4, and trophoblast vesicles (TBVs) were created in suspension. The expression pattern of extravillous trophoblast (EVT) genes was compared between translocated and control TBVs. The functional properties of the TBVs were evaluated by their attachment to endometrium cells (ECC1) and invasion through trans-well inserts.

Results: TBVs derived from control hESCs expressed EVT genes from functioning trophoblast cells. In contrast, TBVs differentiated from the translocated hESC line displayed impaired expression of EVT genes. Moreover, the number of TBVs that were attached to endometrium cells was significantly lower compared to the controls. Correspondingly, invasiveness of trophoblast-differentiated translocated cells was also significantly lower than that of the control cells.

Conclusions: These results may explain the reason for implantation failure in couple carriers of t(11;22). They also demonstrate that translocated hESCs comprise a valuable in vitro human model for studying the mechanisms underlying implantation failure.

Citing Articles

Stem Cell-Based Trophoblast Models to Unravel the Genetic Causes of Human Miscarriages.

Nikitina T, Lebedev I Cells. 2022; 11(12).

PMID: 35741051 PMC: 9221414. DOI: 10.3390/cells11121923.

Specification of trophoblast from embryonic stem cells exposed to BMP4.

Roberts R, Ezashi T, Sheridan M, Yang Y Biol Reprod. 2018; 99(1):212-224.

PMID: 29579154 PMC: 6044404. DOI: 10.1093/biolre/ioy070.

References

Das M, Holzer H . Recurrent implantation failure: gamete and embryo factors. Fertil Steril. 2012; 97(5):1021-7. DOI: 10.1016/j.fertnstert.2012.02.029. View

Staun-Ram E, Shalev E . Human trophoblast function during the implantation process. Reprod Biol Endocrinol. 2005; 3:56. PMC: 1289292. DOI: 10.1186/1477-7827-3-56. View

Elghezal H, Hidar S, Mougou S, Khairi H, Saad A . Prevalence of chromosomal abnormalities in couples with recurrent miscarriage. Fertil Steril. 2007; 88(3):721-3. DOI: 10.1016/j.fertnstert.2006.11.160. View

Hirano T, Higuchi T, Katsuragawa H, Inoue T, Kataoka N, Park K . CD9 is involved in invasion of human trophoblast-like choriocarcinoma cell line, BeWo cells. Mol Hum Reprod. 1999; 5(2):168-74. DOI: 10.1093/molehr/5.2.168. View

Roberts R, Fisher S . Trophoblast stem cells. Biol Reprod. 2010; 84(3):412-21. PMC: 3043125. DOI: 10.1095/biolreprod.110.088724. View

Evsikov S, Cieslak J, Verlinsky Y . Effect of chromosomal translocations on the development of preimplantation human embryos in vitro. Fertil Steril. 2000; 74(4):672-7. DOI: 10.1016/s0015-0282(00)01513-2. View

Franssen M, Musters A, van der Veen F, Repping S, Leschot N, Bossuyt P . Reproductive outcome after PGD in couples with recurrent miscarriage carrying a structural chromosome abnormality: a systematic review. Hum Reprod Update. 2011; 17(4):467-75. DOI: 10.1093/humupd/dmr011. View

Drukker M, Tang C, Ardehali R, Rinkevich Y, Seita J, Lee A . Isolation of primitive endoderm, mesoderm, vascular endothelial and trophoblast progenitors from human pluripotent stem cells. Nat Biotechnol. 2012; 30(6):531-42. PMC: 3672406. DOI: 10.1038/nbt.2239. View

Fraccaro M, LINDSTEN J, Ford C, Iselius L . The 11q;22q translocation: a European collaborative analysis of 43 cases. Hum Genet. 1980; 56(1):21-51. DOI: 10.1007/BF00281567. View

10.

Ben-Yosef D, Malcov M, Eiges R . PGD-derived human embryonic stem cell lines as a powerful tool for the study of human genetic disorders. Mol Cell Endocrinol. 2008; 282(1-2):153-8. DOI: 10.1016/j.mce.2007.11.010. View

11.

Gonzalez M, Neufeld J, Reimann K, Wittmann S, Samalecos A, Wolf A . 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 β. Mol Hum Reprod. 2011; 17(7):421-33. DOI: 10.1093/molehr/gar015. View

12.

Lash G, Hornbuckle J, Brunt A, Kirkley M, Searle R, Robson S . Effect of low oxygen concentrations on trophoblast-like cell line invasion. Placenta. 2006; 28(5-6):390-8. DOI: 10.1016/j.placenta.2006.06.001. View

13.

Thomson J, Itskovitz-Eldor J, Shapiro S, Waknitz M, Swiergiel J, Marshall V . Embryonic stem cell lines derived from human blastocysts. Science. 1998; 282(5391):1145-7. DOI: 10.1126/science.282.5391.1145. View

14.

Reubinoff B, Pera M, Fong C, Trounson A, Bongso A . Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nat Biotechnol. 2000; 18(4):399-404. DOI: 10.1038/74447. View

15.

Moindjie H, Santos E, Loeuillet L, Gronier H, de Mazancourt P, Barnea E . Preimplantation factor (PIF) promotes human trophoblast invasion. Biol Reprod. 2014; 91(5):118. DOI: 10.1095/biolreprod.114.119156. View

16.

Cohen M, Bischof P . Factors regulating trophoblast invasion. Gynecol Obstet Invest. 2007; 64(3):126-30. DOI: 10.1159/000101734. View

17.

Giakoumopoulos M, Golos T . Embryonic stem cell-derived trophoblast differentiation: a comparative review of the biology, function, and signaling mechanisms. J Endocrinol. 2013; 216(3):R33-45. PMC: 3809013. DOI: 10.1530/JOE-12-0433. View

18.

Wagner P, Otomo A, Christians J . Regulation of pregnancy-associated plasma protein A2 (PAPPA2) in a human placental trophoblast cell line (BeWo). Reprod Biol Endocrinol. 2011; 9:48. PMC: 3096916. DOI: 10.1186/1477-7827-9-48. View

19.

Weimar C, Post Uiterweer E, Teklenburg G, Heijnen C, Macklon N . In-vitro model systems for the study of human embryo-endometrium interactions. Reprod Biomed Online. 2013; 27(5):461-76. DOI: 10.1016/j.rbmo.2013.08.002. View

20.

Aplin J . In vitro analysis of trophoblast invasion. Methods Mol Med. 2006; 122:45-57. DOI: 10.1385/1-59259-989-3:45. View