Fetal microchimerism and prenatal diagnostic of genetic disorders

Home/2016, Vol. 4, No. 1/Fetal microchimerism and prenatal diagnostic of genetic disorders

Cell and Organ Transplantology. 2016; 4(1):124-131.
DOI: 10.22494/COT.V4I1.2

Fetal microchimerism and prenatal diagnostic of genetic disorders

Lutsenko T. M.
State Institute of Genetic and Regenerative Medicine NAMS, Kyiv, Ukraine

It is often require an invasive diagnosis based on karyotyping of cells from amniotic fluid, chorionic villi and cord blood in case of the fetus pathologies during pregnancy. The performance of these procedures has a risk of pregnancy complications or procedure-induced miscarriage. Therefore the investigators have nowadays been developing several approaches which would be capable to replace invasive diagnosis by alternative and safe non-invasive methods for detection of possible pregnancy pathology. Fetal microchimerism phenomenon and reliable strategies of fetal cells enrichment during early embryogenesis are reviewed. Fetal cells circulating in the peripheral blood of pregnant women has been described as a potential source of fetus genetic material in non-invasive prenatal diagnosis for chromosomal aberrations.

Key words: pregnancy, fetal microchimerism, chromosomal abnormalities, prenatal genetic screening

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1. Firth HV, Boyd PA, Chamberlain PF, et al. Analysis of limb reduction defects in babies exposed to chorionic villus sampling. Lancet. 1994; 343(8905): 1069-71.
2. Kollmann M, Haeusler M, Haas J, et al. Procedure-related complications after genetic amniocentesis and chorionic villus sampling. Ultraschall. Med. 2013; 34(4): 345-48.
3. Tabor A, Philip J, Madsen M, et al. Randomised controlled trial of genetic amniocentesis in 4606 low-risk women. Lancet. 1986; 1(8493): 1287-93.
4. Norwitz ER, Levy B. Noninvasive prenatal testing: the future is now. Rev. Obstet. Gynecol. 2013; 6(2): 48-62.
PMid:24466384 PMCid:PMC3893900
5. Migliaccio G, Migliaccio AR, Petti S, et al. Human embryonic hemopoiesis. Kinetics of progenitors and precursors underlying the yolk sac-liver transition. J Clin Invest. 1986; 78(1): 51-60.
PMid:3722384 PMCid:PMC329530
6. Thomas MR, Williamson R, Craft I, et al. Y chromosome sequence DNA amplified from peripheral blood of women in early pregnancy. Lancet. 1994; 343(8894): 413-14.
7. Millar DS, Davis LR, Rodeck CH, et al. Normal blood cell values in the early mid-trimester fetus. Prenat Diagn.1985; 5(6): 367-73.
8. de Waele M, Foulon W, Renmans W, et al. Hematologic values and lymphocyte subsets in fetal blood. Am J Clin Pathol. 1988; 89(6): 742-46.
9. Forestier F, Daffos F, Catherine N, et al. Developmental hematopoiesis in normal human fetal blood. Blood.1991; 77(11): 2360-63.
10. Ariga H, Ohto H, Busch MP, et al. Kinetics of fetal cellular and cell-free DNA in the maternal circulation during and after pregnancy: implications for noninvasive prenatal diagnosis. Transfusion. 2000; 41(12): 1524-30.
11. Lo YM, Lau TK, Chan LY, et al. Quantitative analysis of the bidirectional fetomaternal transfer of nucleated cells and plasma DNA. Clin. Chem. 2000; 46(9):1301-09.
12. Campagnoli C, Roberts IA, Kumar S, et al. Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood. 2001; 98(8): 2396-402.
13. Mikhail MA, M’Hamdi H, Welsh J, et al. High frequency of fetal cells within a primitive stem cell population in maternal blood. Hum Reprod. 2008; 23(4): 928-33.
14. Khosrotehrani K, Johnson KL, Cha DH, et al. Transfer of fetal cells with multilineage potential to maternal tissue. JAMA. 2004; 292(1): 75-80.
15. Pritchard S, Hoffman AM, Johnson KL, et al. Pregnancy-associated progenitor cells: an under-recognized potential source of stem cells in maternal lung. Placenta. 2011; 32(4): 298-303.
PMid:21546085 PMCid:PMC3157495
16. Bianchi DW. Fetomaternal cell traffic, pregnancy-associated progenitor cells, and autoimmune disease. Best Pract Res Clin Obstet Gynaecol. 2004; 18(6): 959-75.
17. Pineda-Krch M, Lehtilä K. Costs and benefits of genetic heterogeneity within. J Evol Biol. 2004; 17(6): 1167–77.
18. Allyse M, Minear MA, Berson E, et al. Non-invasive prenatal testing: a review of international implementation and challenges. Int J Womens Health. 2015; 16(7): 113-26.
PMid:25653560 PMCid:PMC4303457
19. Ho SS, O’Donoghue K, Choolani M. Fetal cells in maternal blood: state of the art for non-invasive prenatal diagnosis. Ann Acad Med Singapore. 2003; 32(5): 597-603.
20. Iverson GM, Bianchi DW, Cann HM, et al. Detection and isolation of fetal cells from maternal blood using the flourescence-activated cell sorter (FACS). Prenat Diagn. 1981; 1(1): 61-73.
21. Tavian M, Coulombel L, Luton D, et al. Aorta-Associated CD34+ Hematopoietic Cells in the Early Human Embry. Blood. 1996; 87(1): 67-72.
22. Nierhoff D, Levoci L, Schulte S, et al. New cell surface markers for murine fetal hepatic stem cells identified through high density complementary DNA microarrays. Hepatology. 2007; 46(2): 535-47.
23. Pritchard S, Wick H, Slonim D, et al. Comprehensive Analysis of Genes Expressed by Rare Microchimeric Fetal Cells in the Maternal Mouse Lung. Biol Reprod. 2012; 87(2): 42. doi:10.1095/biolreprod.112.101147
24. Brinch M, Hatt L, Singh R, et al. Identification of circulating fetal cell markers by microarray analysis. Prenat Diagn. 2012; 32(8): 742-51.
25. Hatt L, Brinch M, Singh R, et al. Characterization of fetal cells from the maternal circulation by microarray gene expression analysis–could the extravillous trophoblasts be a target for future cell-based non-invasive prenatal diagnosis? Fetal Diagn Ther. 2013; 35(3): 218-27.
26. Hatt L, Brinch M, Singh R, et al. A new marker set that identifies fetal cells in maternal circulation with high specificity. Prenat Diagn. 2014; 34(11): 1066-72.
27. Sipos PI, Rens W, Schlecht H, et al. Uterine vasculature remodeling in human pregnancy involves functional macrochimerism by endothelial colony forming cells of fetal origin. Stem Cells. 2013; 31(7): 1363-70.
PMid:23554274 PMCid:PMC3813980
28. Mahmood U, O’Donoghue K. Microchimeric fetal cells play a role in maternal wound healing after pregnancy. Chimerism. 2014; 5(2): 40-52.
PMid:24717775 PMCid:PMC4199806
29. Cirello V, Rizzo R, Crippa M, et al. Fetal cell microchimerism: a protective role in autoimmune thyroid diseases. Eur J Endocrinol. 2015; 173(1): 111-18.
30. Covone AE, Kozma R, Johnson PM, et al. Analysis of peripheral maternal blood samples for the presence of placenta-derived cells using Y-specific probes and McAb H315. Prenat Diagn. 1988; 8(8): 591-607.
31. Committee Opinion No. 581: the use of chromosomal microarray analysis in prenatal diagnosis. Obstet Gynecol. 2013; 122(581): 1374-1377. doi: 10.1097/01.AOG.0000438962.16108.d1
32. Lau TK, Chan MK, Lo PS, et al. Clinical utility of noninvasive fetal trisomy (NIFTY) test – early experience. The Journal of Maternal-Fetal and Neonatal Medicine. 2012; 25(10): 1856-59.
PMid:22471583 PMCid:PMC3483059
33. Manegold-Brauer G, Kang Bellin A, Hahn S, et al. A new era in prenatal care: non-invasive prenatal testing in Switzerland. Swiss Med Wkly. 2014; 4(144): w13915.
34. Debeljak M, Freed DN, Welch JA, et al. Haplotype counting by next-generation sequencing for ultrasensitive human DNA detection. J Mol Diagn. 2014; 16(5): 495-503.
35. Everett TR, Chitty LS. Cell-free fetal DNA: the new tool in fetal medicine. Ultrasound Obstet Gynecol. 2015; 45(5): 499-507.
PMid:25483938 PMCid:PMC5029578
36. Xu XP, Gan HY, Li FX, et al. A Method to Quantify Cell-Free Fetal DNA Fraction in Maternal Plasma Using Next Generation Sequencing: Its Application in Non-Invasive Prenatal Chromosomal Aneuploidy Detection. PLoS One. 2016; 11(1): e0146997.
PMid:26765738 PMCid:PMC4713075
37. Goodfellow CF, Taylor PV. Extraction and identification of trophoblast cells circulating in peripheral blood during pregnancy. Br J Obstet Gynaecol. – 1982; 89(1): 65-68.
38. Chua S, Wilkins T, Sargent I, et al. Trophoblast deportation in pre-eclamptic pregnancy. Br J Obstet Gynaecol. 1991; 98(10): 973-79.
39. Szwajcowska M, Kalinka J, Krajewski P. Nucleated red blood cells (nRBC) as an auxiliary marker of intrauterine infection. J Ped Neonatal. 2005; 2(1): 15-18.
40. Gänshirt D, Garritsent H, Holzgreve W, et al. Fetal cells in maternal blood. Curr. Opin. Obstet. Gyn. 1995; 7(2): 103-8.
41. Nguyen HS, Dubernard G, Aractingi S, et al. Feto-maternal cell trafficking: a transfer of pregnancy associated progenitor cells. Stem Cell Rev. 2006; 2(2): 111–16.
42. Bianchi DW, Zickwolf GK, Weil GJ, et al. Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum. Proc Natl Acad Sci USA. 1996; 93(2): 705–8.
PMid:8570620 PMCid:PMC40117
43. Khosrotehrani K, Reyes RR, Johnson KL, et al. Fetal cells participate over time in the response to specific types of murine maternal hepatic injury. Hum Reprod. 2007; 22(3): 654-61.
44. Covone AE, Mutton D, Johnson PM, et al. Trophoblast cells in peripheral blood from pregnant women. Lancet.1984; 2(8407): 841-43.
45. Hengstschläger M, Bernaschek G. Fetal cells in the peripheral blood of pregnant women express thymidine kinase: a new marker for detection. FEBS Lett.1997; 404(2-3): 299-302.
46. Sargent JL, Johansen M, Chua S, et al. Clinical Experience: Isolating Trophoblasts from Maternal Blood. Annals of the New York Academy of Sciences. 1994; 731(1):154-61.
47. Goldberg JD, Wohlferd MM. Incidence and outcome of chromosomal mosaicism found at the time of chorionic villus sampling. Am J Ohstet Gynecol. 1997; 176(6): 1349-52.
48. Henderson KG, Shaw TE, Barrett IJ, et al. Distribution of mosaicism in human placentae. Hum Genet.1996; 97(5): 650-54.
49. Benirschke K, Willes L. Deportation of trophoblastic emboli to maternal lung. A source of cell-free DNA in maternal blood? Chimerism. 2010; 1(1): 15-18.
PMid:21327145 PMCid:PMC3035106
50. Manegold-Brauer G, Hahn S, Lapaire O. What does next-generation sequencing mean for prenatal diagnosis? Biomark Med. 2014; 8(4): 499-508.
51. Huyhn A, Dommergues M, Izac B, et al. Characterization of hematopoietic progenitors from human yolk sacs and embryos. Blood. 1995; 86(12): 4474-85.
52. Loken MR, Civin CI, Bigbee WL, et al. Coordinate glycosylation and cell surface expression of glycophorin A during normal human erythropoiesis. Blood.1987; 70(6): 1959-61.
53. Bianchi DW, Flint AF, Pizzimenti MF, et al. Isolation of fetal DNA from nucleated erythrocytes in maternal blood. Proc Natl Acad Sci USA. 1990; 87(9): 3279-83.
PMid:2333281 PMCid:PMC53883
54. Zheng YL, Demaria M, Zhen D, et al. Flow sorting of fetal erythroblasts using intracytoplasmic anti-fetal haemoglobin: preliminary observations on maternal samples. Prenat Diagn. 1995; 15(10): 897-905.
55. Mesker WE, Ouwerkerk-van Velzen MC, Oosterwijk JC, et al. Two-colour immunocytochemical staining of gamma (gamma) and epsilon (epsilon) type haemoglobin in fetal red cells. Prenat Diagn. 1998; 18(11): 1131-37.
56. Bianchi DW. Fetal cells in the maternal circulation: feasibility for prenatal diagnosis. British J Haematol. 1999. 105(3): 574–83.
57. van Wijk IJ, van Vugt JM, Mulders MA, et al. Enrichment of fetal trophoblast cells from the maternal peripheral blood followed by detection of fetal deoxyribonucleic acid with a nested X/Y polymerase chain reaction. Am J Obstet Gynecol. 1996. 174(3): 871-78.
58. Pearson HA. Life-span of the fetal red blood cell. The Journal of Pediatrics. 1967; 70(2): 166–71.
59. Simpson JL, Elias S. Isolating fetal cells in maternal circulation lor prenatal diagnosis . Prenat Diagn. 1994; 14(13): 1229-1242.
60. Choolani M, O’Donoghue K, Talbert D, et al. Characterization of first trimester fetal erythroblasts for non-invasive prenatal diagnosis. Mol Hum Reprod. 2003; 9(4): 227-235.
61. Price JO, Elias S, Wachtel SS. Prenatal diagnosis with fetal cells isolated from maternal blood by multiparameter flow cytometry. Am J Obstet Gynecol. 1991; 165(6Pt1): 1731-37.
62. Troeger C, Holzgreve W, Hahn S. A comparison of different density gradients and antibodies for enrichment of fetal erythroblasts by MACS. Prenat. Diagn. 1999; 19(6): 521-26.
63. Al-Mufti R, Hambley H, Farzaneh F, et al. Distribution of fetal and embryonic hemoglobins in fetal erythroblasts enriched from maternal blood. Haematologica. 2001; 86(4): 357-62.
64. Kølvraa S, Christensen B, Lykke-Hansen L, et al. The Fetal Erythroblast Is Not the Optimal Target for Non-invasive Prenatal Diagnosis: Preliminary Results. J Histochem Cytochem. 2005; 53(3): 331-36.
65. Walknowska J, Conte FA, Grumbach MM. Practical and theoretical implications of fetal-maternal lymphocyte transfer. Lancet. 1969; 1(7606): 1119-22.
66. Herzenberg LA, Bianchi DW, Schröder J, et al. Fetal cells in the blood of pregnant women: detection and enrichment by fluorescence-activated cell sorting. Proc. Natl. Acad. Sci. USA. 1979; 76(3): 1453-55.
67. Sunami R, Komuro M, Tagaya H, et al. Migration of microchimeric fetal cells into maternal circulation before placenta formation. Chimerism. 2010; 1(2): 66-8.
PMid:21327051 PMCid:PMC3023627
68. Sunami R, Komuro M, Yuminamochi T, et al. Fetal cell microchimerism develops through the migration of fetus-derived cells to the maternal organs early after implantation. J Reprod Immunol. 2010; 84(2): 117-23.
69. Wang Y, Iwatani H, Ito T, et al. Fetal cells in mother rats contribute to the remodeling of liver and kidney after injury. Biochem Biophys Res Commun. 2004; 325(3): 961-67.
70. Tan XY, Liao H, Sun L, et al. Fetal microchimerism in the maternal brain: A novel population of fetal progenitor or stem cells able to cross the blood-brain barrier? Stem Cells. 2005; 23(10): 1443-52.
71. Rina Kara J, Bolli P, Karakikes I, et al. Fetal Cells Traffic to Injured Maternal Myocardium nd Undergo Cardiac Differentiation. Circulation Research. 2012; 110(1): 82-93.
PMid:22082491 PMCid:PMC3365532
72. Nguyen HS, Oster M, Uzan S. Maternal neoangiogenesis during pregnancy partly derives from fetal endothelial progenitor cells. Proc Natl Acad Sci USA. 2007; 104(6): 1871-76.
PMid:17267612 PMCid:PMC1794298
73. Zhong JF, Weiner LP. Role of Fetal Stem Cells in Maternal Tissue Regeneration. Gene Regul Syst Bio. 2007; 1: 111–115.
PMid:19936082 PMCid:PMC2759120
74. O’Donoghue K, Choolani M, Chan J, et al. Identification of fetal mesenchymal stem cells in maternal blood: implications for non-invasive prenatal diagnosis. Mol Hum Reprod. 2003; 9(8): 497-502.
75. Kaufmann P, Black S, Huppertz B. Endovascular trophoblast invasion: implications for the pathogenesis of intrauterine growth retardation and preeclampsia. Biol Reprod. 2003; 69(1): 1-7.
76. Harris LK. Review: trophoblast-vascular cell interactions in early pregnancy: how to remodel a vessel. Placenta. 2010; S93-8. doi: 10.1016/j.placenta.2009.12.012
77. Zhou Y, Fisher SJ, Janatpour M, et al. Human cytotrophoblasts adopt a vascular phenotype as they differentiate. A strategy for successful endovascular invasion?. J Clin Invest.1997; 99(9): 2139-51.
PMid:9151786 PMCid:PMC508044
78. Gordon MY, Levicar N, Pai M, et al. Characterization and clinical application of human CD34+ stem/progenitor cell populations mobilized into the blood by granulocyte colony-stimulating factor. Stem Cells. 2006; 24(7): 1822-30.
79. Parant O, Dubernard G, Challier JC, et al. CD34+ cells in maternal placental blood are mainly fetal in origin and express endothelial markers. Lab Invest. 2009; 89(8): 915-23.
80. O’Donoghue K, Chan J, de la Fuente J, et al. Microchimerism in female bone marrow and bone decades after fetal mesenchymal stem-cell trafficking in pregnancy. Lancet. 2004; 364(9429): 179-82.
81. Guillot PV, Gotherstrom C, Chan J, et al. Human first-trimester fetal MSC express pluripotency markers and grow faster and have longer telomeres than adult MSC. Stem Cells. 2007; 25(3): 646-54.
82. Kennea NL, Waddington SN, Chan J, et al. Differentiation of human fetal mesenchymal stem cells into cells with an oligodendrocyte phenotype .Cell Cycle. 2009; 8(7): 1069-79.
83. Wu G, Schöler HR. Role of Oct4 in the early embryo development. Cell Regen (Lond). 2014; 3(1). doi: 10.1186/2045-9769-3-7
84. Zheng S, Tong X, Wu L, et al. A comparison of in vitro culture of fetal nucleated erythroblasts from fetal chorionic villi and maternal peripheral blood for noninvasive prenatal diagnosis. Fetal Diagn Ther. 2012; 32(3): 194-200.
85. Risau W. Embryonic angiogenesis factors. Pharmacol Ther.1991; 51(3): 371-76.
86. Risau W, Flamme I. Vasculogenesis . Annu Rev Cell Dev Biol. 1995; 11:73-91.
87. Gussin HA, Bischoff FZ, Hoffman R, et al. Endothelial precursor cells in the peripheral blood of pregnant women. J Soc Gynecol Investig. 2002; 9(6): 357-61.
88. Rafii S. Circulating endothelial precursors: mystery, reality, and promise. J Clin Invest. 2000; 105(1): 17-19.
PMid:10619857 PMCid:PMC382591
89. Gussin HA, Elias S. Culture of fetal cells from maternal blood for prenatal diagnosis. Hum Reprod Update. 2002; 8(6): 523-27.
90. Lo YM, Tein MS, Lau TK, et al. Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am. J. Hum. Genet. 1998; 62(4): 768–75.
PMid:9529358 PMCid:PMC1377040
91. Van der Schoot CE, Hahn S, Chitty LS Non-invasive prenatal diagnosis and determination of fetal Rh status. Semin. Fetal Neonatal Med. 2008; 13(2): 63-8.
92. Ehrich M, Deciu C, Zwiefelhofer T, et al. No-ninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting. Am. J. Obstet. Gynecol. 2011; 204(3): 205.e1-11.
93. Palomaki GE, Kloza EM, Lambert-Messerlian GM, et al. DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study. Genet Med. 2011; 13(11): 913-20.
94. Bianchi DW, Platt LD, Goldberg JD, et al. Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing. Obstet. Gynecol. 2012; 119(5): 890-901.
95. Sparks AB, Struble CA, Wang ET, et al. Non-invasive prenatal detection and selective analysis of cell-free DNA obtained from maternal blood: evaluation for trisomy 21 and trisomy 18. Am. J. Obstet. Gynecol. 2012; 206(4): 319.e1-9.
96. Ashoor G, Syngelaki A, Wagner M, et al. Chromosome-selective sequencing of maternal plasma cell-free DNA for first-trimester detection of trisomy 21 and trisomy 18. Am. J. Obstet. Gynecol. 2012; 206(4): 322.e1–5.
97. Norton ME, Brar H, Weiss J, et al. Non-Invasive Chromosomal Evaluation (NICE) Study: results of a multicenter prospective cohort study for detection of fetal trisomy 21 and trisomy 18. Am. J. Obstet. Gynecol. 2012; 207(2): 137.e1–8.
98. Zimmermann B, Hill M, Gemelos G, et al. Noninvasive prenatal aneuploidy testing of chromosomes 13, 18, 21, X, and Y, using targeted sequencing of polymorphic loci. Prenat Diagn. 2012; 32(13): 1233-41.
PMid:23108718 PMCid:PMC3548605
99. Nicolaides KH, Syngelaki A, Gil M, et al. Validation of targeted sequencing of single-nucleotide polymorphisms for non-invasive prenatal detection of aneuploidy of chromosomes 13, 18, 21, X, and Y. Prenat. Diagn. 2013; 33(6): 575-79.
100. Samango-Sprouse C, Banjevic M, Ryan A, et al. SNP-based non-invasive prenatal testing detects sex chromosome aneuploidies with high accuracy. Prenat. Diagn. 2013; 33(7): 643-49.
PMid:23712453 PMCid:PMC3764608

Lutsenko TM. Fetal microchimerism and prenatal diagnostic of genetic disorders. Cell and Organ Transplantology. 2016; 4(1):124-131. doi: 10.22494/COT.V4I1.2


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