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Umbilical Cord Maternal Microchimerism in Normal and Preeclampsia Pregnancies

  • Maternal Fetal Medicine/Biology: Original Article
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Abstract

Bidirectional exchange of cells between mother and fetus establishes microchimerism (Mc). Mc can persist for decades and is associated with later-life health and disease. Greater fetal Mc is detected in the maternal compartment in preeclampsia (PE), but whether maternal Mc (MMC) in umbilical cord blood (CB) is altered in PE is unknown. We evaluated MMc in CB from normal and PE pregnancies. DNA from CB mononuclear cells following placental delivery (n = 36 PE, n = 37 controls) and maternal blood was extracted and genotyped. MMc, quantified by qPCR assays targeting maternal-specific nonshared polymorphisms in CB, was compared using logistic and negative binomial regression models. Clinically and statistically relevant confounders were included, and included the total number of cell equivalents tested, gravidity, mode of delivery, birthweight, and fetal sex. PE participants delivered at earlier gestational ages, with higher Cesarean rates, and lower infant birthweights. CB MMc detection was similar between PE and controls (52.8% vs. 51.3%, respectively, p = 0.90) and unchanged after adjustment for confounders. MMc concentration was not different between groups (mean 73.7 gEq/105 gEq in PE vs. mean 22.8 gEq/105 in controls, p = 0.56), including after controlling for confounders (p = 0.64). There was no difference in CB MMc detection or concentration between PE and normal pregnancies, despite previously noted greater fetal Mc in the maternal compartment. This suggests possible differential transfer of cells at the maternal fetal interface in PE. Phenotypic evaluation of Mc cells may uncover underlying mechanisms for differential cellular exchange between mother and fetus in PE.

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References

  1. Lo YM, et al. Two-way cell traffic between mother and fetus: biologic and clinical implications. Blood. 1996;88(11):4390–5.

    Article  CAS  PubMed  Google Scholar 

  2. Adams Waldorf KM, et al. Dynamic changes in fetal microchimerism in maternal peripheral blood mononuclear cells, CD4+ and CD8+ cells in normal pregnancy. Placenta. 2010;31(7):589–94. https://doi.org/10.1016/j.placenta.2010.04.013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Nelson JL. The otherness of self: microchimerism in health and disease. Trends Immunol. 2012;33(8):421–7. https://doi.org/10.1016/j.it.2012.03.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Gammill HS, Harrington WE. Microchimerism: defining and redefining the prepregnancy context — a review. Placenta. 2017;60:130–3. https://doi.org/10.1016/j.placenta.2017.08.071.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Chen C-P, et al. Trafficking of multipotent mesenchymal stromal cells from maternal circulation through the placenta involves vascular endothelial growth factor receptor-1 and integrins. Stem Cells. 2008;26(2):550–61. https://doi.org/10.1634/stemcells.2007-0406.

    Article  CAS  PubMed  Google Scholar 

  6. Hall JM, Lingenfelter P, Adams SL, Lasser D, Hansen JA, Bean MA. Detection of maternal cells in human umbilical cord blood using fluorescence in situ hybridization. Blood. 1995;86(7):2829–32.

    Article  CAS  PubMed  Google Scholar 

  7. Petit T, Dommergues M, Socié G, Dumez Y, Gluckman E, Brison O. Detection of maternal cells in human fetal blood during the third trimester of pregnancy using allele-specific PCR amplification. Br J Haematol. 1997;98(3):767–71.

    Article  CAS  PubMed  Google Scholar 

  8. Jonsson AM, Uzunel M, Götherström C, Papadogiannakis N, Westgren M. Maternal microchimerism in human fetal tissues. Am J Obstet Gynecol. 2008;198(3):325.e1-6. https://doi.org/10.1016/j.ajog.2007.09.047.

    Article  CAS  PubMed  Google Scholar 

  9. Mold JE, et al. Maternal alloantigens promote the development of tolerogenic fetal regulatory T cells in utero. Science. 2008;322(5907):1562–5. https://doi.org/10.1126/science.1164511.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Dutta P, et al. Microchimerism is strongly correlated with tolerance to noninherited maternal antigens in mice. Blood. 2009;114(17):3578–87. https://doi.org/10.1182/blood-2009-03-213561.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Buxmann H, et al. Maternal CD4+ microchimerism in HIV-exposed newborns after spontaneous vaginal delivery or caesarean section. Early Hum Dev. 2016;98:49–55. https://doi.org/10.1016/j.earlhumdev.2016.06.004.

    Article  CAS  PubMed  Google Scholar 

  12. Tapia G, et al. Maternal microchimerism in cord blood and risk of childhood-onset type 1 diabetes. Pediatr Diabetes. 2019;20(6):728–35. https://doi.org/10.1111/pedi.12875.

    Article  CAS  PubMed  Google Scholar 

  13. Tapia G, et al. Maternal microchimerism in cord blood and risk of celiac disease in childhood. J Pediatr Gastroenterol Nutr. 2020;71(3):321–7. https://doi.org/10.1097/MPG.0000000000002811.

    Article  CAS  PubMed  Google Scholar 

  14. Opstelten R, et al. Determining the extent of maternal-foetal chimerism in cord blood. Sci Rep. 2019;9(1):5247. https://doi.org/10.1038/s41598-019-41733-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kanold AMJ, Westgren M, Götherström C. Cellular subsets of maternal microchimerism in umbilical cord blood. Cell Transplant. 2019;28(5):522–8. https://doi.org/10.1177/0963689718779783.

    Article  PubMed  Google Scholar 

  16. Haddad ME, et al. Factors predicting the presence of maternal cells in cord blood and associated changes in immune cell composition. Front Immunol. 2021;12:651399. https://doi.org/10.3389/fimmu.2021.651399.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kanaan SB, et al. Maternal microchimerism is prevalent in cord blood in memory T cells and other cell subsets, and persists post-transplant. Oncoimmunology. 2017;6(5):e1311436. https://doi.org/10.1080/2162402X.2017.1311436.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Rowe JH, Ertelt JM, Xin L, Way SS. Pregnancy imprints regulatory memory that sustains anergy to fetal antigen. Nature. 2012;490(7418):102–6. https://doi.org/10.1038/nature11462.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Santner-Nanan B, et al. Systemic increase in the ratio between Foxp3+ and IL-17-producing CD4+ T cells in healthy pregnancy but not in preeclampsia. J Immunol. 2009;183(11):7023–30. https://doi.org/10.4049/jimmunol.0901154.

    Article  CAS  PubMed  Google Scholar 

  20. Stevens AM, Hermes HM, Kiefer MM, Rutledge JC, Nelson JL. Chimeric maternal cells with tissue-specific antigen expression and morphology are common in infant tissues. Pediatr Dev Pathol. 2009;12(5):337–46. https://doi.org/10.2350/08-07-0499.1.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Srivatsa B, Srivatsa S, Johnson KL, Bianchi DW. Maternal cell microchimerism in newborn tissues. J Pediatr. 2003;142(1):31–5. https://doi.org/10.1067/mpd.2003.mpd0327.

    Article  PubMed  Google Scholar 

  22. Peterson SE, et al. Prospective assessment of fetal-maternal cell transfer in miscarriage and pregnancy termination. Hum Reprod. 2012;27(9):2607–12. https://doi.org/10.1093/humrep/des244.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Shree R, et al. Fetal microchimerism by mode of delivery: a prospective cohort study. BJOG. 2019;126(1):24–31. https://doi.org/10.1111/1471-0528.15432.

    Article  CAS  PubMed  Google Scholar 

  24. Khan KS, Wojdyla D, Say L, Gülmezoglu AM, Van Look PF. WHO analysis of causes of maternal death: a systematic review. Lancet. 2006;367(9516):1066–74. https://doi.org/10.1016/S0140-6736(06)68397-9.

    Article  PubMed  Google Scholar 

  25. Shih T, et al. The rising burden of preeclampsia in the United States impacts both maternal and child health. Am J Perinatol. 2016;33(4):329–38. https://doi.org/10.1055/s-0035-1564881.

    Article  PubMed  Google Scholar 

  26. Backes CH, Markham K, Moorehead P, Cordero L, Nankervis CA, Giannone PJ. Maternal preeclampsia and neonatal outcomes. J Pregnancy. 2011;2011. https://doi.org/10.1155/2011/214365

  27. Yıldırım G, Güngördük K, Aslan H, Gül A, Bayraktar M, Ceylan Y. Comparison of perinatal and maternal outcomes of severe preeclampsia, eclampsia, and HELLP syndrome. J Turk Ger Gynecol Assoc. 2011;12(2):90–6. https://doi.org/10.5152/jtgga.2011.22.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Gammill HS, Aydelotte TM, Guthrie KA, Nkwopara EC, Nelson JL. Cellular fetal microchimerism in preeclampsia. Hypertension. 2013;62(6):1062–7.

    Article  CAS  PubMed  Google Scholar 

  29. Pollack MS, Kirkpatrick D, Kapoor N, Dupont B, O’Reilly RJ. Identification by HLA typing of intrauterine-derived maternal T cells in four patients with severe combined immunodeficiency. N Engl J Med. 1982;307(11):662–6. https://doi.org/10.1056/NEJM198209093071106.

    Article  CAS  PubMed  Google Scholar 

  30. Maloney S, et al. Microchimerism of maternal origin persists into adult life. J Clin Invest. 1999;104(1):41–7. https://doi.org/10.1172/JCI6611.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lu HQ, Hu R. Lasting effects of intrauterine exposure to preeclampsia on offspring and the underlying mechanism. AJP Rep. 2019;9(3):e275–91. https://doi.org/10.1055/s-0039-1695004.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Gestational hypertension and preeclampsia: ACOG practice bulletin, Number 222. Obstet Gynecol. 2020;135(6):e237. https://doi.org/10.1097/AOG.0000000000003891.

  33. Gammill HS, Stephenson MD, Aydelotte TM, Nelson JL. Microchimerism in recurrent miscarriage. Cell Mol Immunol. 2014;11(6):589–94. https://doi.org/10.1038/cmi.2014.82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Lambert NC, et al. Quantification of maternal microchimerism by HLA-specific real-time polymerase chain reaction: studies of healthy women and women with scleroderma. Arthritis Rheum. 2004;50(3):906–14. https://doi.org/10.1002/art.20200.

    Article  CAS  PubMed  Google Scholar 

  35. Kanaan SB, Sensoy O, Yan Z, Gadi VK, Richardson ML, Nelson JL. Immunogenicity of a rheumatoid arthritis protective sequence when acquired through microchimerism. Proc Natl Acad Sci. 2019:201904779. https://doi.org/10.1073/pnas.1904779116.

  36. Guthrie KA, et al. Statistical methods for unusual count data: examples from studies of microchimerism. Am J Epidemiol. 2016;184(10):779–86. https://doi.org/10.1093/aje/kww093.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Kinder JM, et al. Cross-generational reproductive fitness enforced by microchimeric maternal cells. Cell. 2015;162(3):505–15. https://doi.org/10.1016/j.cell.2015.07.006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kinder JM, Stelzer IA, Arck PC, Way SS. Immunological implications of pregnancy-induced microchimerism. Nat Rev Immunol. 2017;17(8):483–94. https://doi.org/10.1038/nri.2017.38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Harrington WE, et al. Maternal microchimerism predicts increased infection but decreased disease due to Plasmodium falciparum during early childhood. J Infect Dis. 2017;215(9):1445–51. https://doi.org/10.1093/infdis/jix129.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Stelzer IA, et al. Vertically transferred maternal immune cells promote neonatal immunity against early life infections. Nat Commun. 2021;12(1):4706. https://doi.org/10.1038/s41467-021-24719-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Czernek L, Düchler M. Exosomes as messengers between mother and fetus in pregnancy. Int J Mol Sci. 2020;21(12):E4264. https://doi.org/10.3390/ijms21124264.

    Article  CAS  Google Scholar 

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Funding

This work was supported by the National Institutes of Health (K08HD067221, K08HL150169, R01HL11737).

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Correspondence to Raj Shree.

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Chimerocyte, Inc. had no role in funding this research, providing testing materials, or analyzing results.

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JLN and SBK have ownership interests in Chimerocyte, Inc., for which highly sensitive and specific detection of allogeneic cells/DNA is its core technology. The remaining authors declare no competing financial interests.

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Shree, R., McCartney, S., Cousin, E. et al. Umbilical Cord Maternal Microchimerism in Normal and Preeclampsia Pregnancies. Reprod. Sci. 30, 1157–1164 (2023). https://doi.org/10.1007/s43032-022-01080-0

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  • DOI: https://doi.org/10.1007/s43032-022-01080-0

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