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Neuroscience Bulletin logoLink to Neuroscience Bulletin
. 2013 Dec 17;30(1):81–89. doi: 10.1007/s12264-013-1392-1

Fetal cell microchimerism in the maternal mouse spinal cord

Guohui Zhang 1,3, Yunan Zhao 3, Xin-Min Li 2, Jiming Kong 1,3,
PMCID: PMC5562577  PMID: 24346789

Abstract

Fetal cell microchimerism refers to the persistence of fetal cells in the maternal tissues following pregnancy. It has been detected in peripheral organs and the brain, but its existence in the spinal cord has not been reported. Our aim was to detect fetal cell microchimerism in the spinal cord of maternal mice. C57BL/6 female mice were crossed with GFP transgenic male mice and sacrificed after their first or third delivery. GFP-positive cells, which were presumably from fetuses whose fathers were GFP transgenic, were detected in the spinal cord by fluorescence microscopy and immunohistochemistry. PCR was also performed to detect GFP DNA, which must come from GFP hemizygous fetuses. We found GFP-positive cells and detectable GFP DNA in most of the maternal spinal cords. Twenty percent (1/5) of the mice that were only pregnant once had detectable fetal cells, while 80% (4/5) of those that were pregnant three times had detectable fetal cells. Some fetal cells, which not only emitted green fluorescence but also expressed NeuN, were detected in the spinal cords from maternal mice. These results indicate that fetal cells migrate into the spinal cord of a maternal mouse during and/or after the gestational period, and the fetal cells may differentiate into neurons in the spinal cord.

Keywords: fetal cell microchimerism, green fluorescent protein, spinal cord, mouse

References

  • [1].Ariga H, Ohto H, Busch MP, Imamura S, Watson R, Reed W, et al. Kinetics of fetal cellular and cell-free DNA in the maternal circulation during and after pregnancy: implications for noninvasive prenatal diagnosis. Transfusion. 2001;41:1524–1530. doi: 10.1046/j.1537-2995.2001.41121524.x. [DOI] [PubMed] [Google Scholar]
  • [2].Bianchi DW, Zickwolf GK, Weil GJ, Sylvester S, DeMaria MA. Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum. Proc Natl Acad Sci U S A. 1996;93:705–708. doi: 10.1073/pnas.93.2.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [3].Gadi VK, Nelson JL. Fetal microchimerism in women with breast cancer. Cancer Res. 2007;67:9035–9038. doi: 10.1158/0008-5472.CAN-06-4209. [DOI] [PubMed] [Google Scholar]
  • [4].Koopmans M, Kremer Hovinga IC, Baelde HJ, Fernandes RJ, de Heer E, Bruijn JA, et al. Chimerism in kidneys, livers and hearts of normal women: implications for transplantation studies. Am J Transplant. 2005;5:1495–1502. doi: 10.1111/j.1600-6143.2005.00858.x. [DOI] [PubMed] [Google Scholar]
  • [5].Lu JQ, Joseph JT, Nash RA, Storek J, Stevens AM, Metz LM, et al. Neuroinflammation and demyelination in multiple sclerosis after allogeneic hematopoietic stem cell transplantation. Arch Neurol. 2010;67:716–722. doi: 10.1001/archneurol.2010.117. [DOI] [PubMed] [Google Scholar]
  • [6].Lu JQ, Storek J, Metz L, Yong VW, Stevens AM, Nash RA, et al. Continued disease activity in a patient with multiple sclerosis after allogeneic hematopoietic cell transplantation. Arch Neurol. 2009;66:116–120. doi: 10.1001/archneurol.2008.522. [DOI] [PubMed] [Google Scholar]
  • [7].Matsubara K, Uchida N, Matsubara Y, Hyodo S, Ito M. Detection of fetal cells in the maternal kidney during gestation in the mouse. Tohoku J Exp Med. 2009;218:107–113. doi: 10.1620/tjem.218.107. [DOI] [PubMed] [Google Scholar]
  • [8].O’Donoghue K, Chan J, de la Fuente J, Kennea N, Sandison A, Anderson JR, et al. Microchimerism in female bone marrow and bone decades after fetal mesenchymal stem-cell trafficking in pregnancy. Lancet. 2004;364:179–182. doi: 10.1016/S0140-6736(04)16631-2. [DOI] [PubMed] [Google Scholar]
  • [9].Sawaya HH, Jimenez SA, Artlett CM. Quantification of fetal microchimeric cells in clinically affected and unaffected skin of patients with systemic sclerosis. Rheumatology (Oxford) 2004;43:965–968. doi: 10.1093/rheumatology/keh211. [DOI] [PubMed] [Google Scholar]
  • [10].Khosrotehrani K, Johnson KL, Guegan S, Stroh H, Bianchi DW. Natural history of fetal cell microchimerism during and following murine pregnancy. J Reprod Immunol. 2005;66:1–12. doi: 10.1016/j.jri.2005.02.001. [DOI] [PubMed] [Google Scholar]
  • [11].Artlett CM, Cox LA, Ramos RC, Dennis TN, Fortunato RA, Hummers LK, et al. Increased microchimeric CD4+ T lymphocytes in peripheral blood from women with systemic sclerosis. Clin Immunol. 2002;103:303–308. doi: 10.1006/clim.2002.5222. [DOI] [PubMed] [Google Scholar]
  • [12].Evans PC, Lambert N, Maloney S, Furst DE, Moore JM, Nelson JL. Long-term fetal microchimerism in peripheral blood mononuclear cell subsets in healthy women and women with scleroderma. Blood. 1999;93:2033–2037. [PubMed] [Google Scholar]
  • [13].Guetta E, Gordon D, Simchen MJ, Goldman B, Barkai G. Hematopoietic progenitor cells as targets for non-invasive prenatal diagnosis: detection of fetal CD34+ cells and assessment of post-delivery persistence in the maternal circulation. Blood Cells Mol Dis. 2003;30:13–21. doi: 10.1016/S1079-9796(03)00008-1. [DOI] [PubMed] [Google Scholar]
  • [14].Stevens AM, McDonnell WM, Mullarkey ME, Pang JM, Leisenring W, Nelson JL. Liver biopsies from human females contain male hepatocytes in the absence of transplantation. Lab Invest. 2004;84:1603–1609. doi: 10.1038/labinvest.3700193. [DOI] [PubMed] [Google Scholar]
  • [15].Wang Y, Iwatani H, Ito T, Horimoto N, Yamato M, Matsui I, et al. Fetal cells in mother rats contribute to the remodeling of liver and kidney after injury. Biochem Biophys Res Commun. 2004;325:961–967. doi: 10.1016/j.bbrc.2004.10.105. [DOI] [PubMed] [Google Scholar]
  • [16].Bianchi DW, Robert E. Gross Lecture. Fetomaternal cell trafficking: a story that begins with prenatal diagnosis and may end with stem cell therapy. J Pediatr Surg. 2007;42:12–18. doi: 10.1016/j.jpedsurg.2006.09.047. [DOI] [PubMed] [Google Scholar]
  • [17].Tan XW, Liao H, Sun L, Okabe M, Xiao ZC, Dawe GS. Fetal microchimerism in the maternal mouse brain: a novel population of fetal progenitor or stem cells able to cross the blood-brain barrier? Stem Cells. 2005;23:1443–1452. doi: 10.1634/stemcells.2004-0169. [DOI] [PubMed] [Google Scholar]
  • [18].Hedlund E, Hefferan MP, Marsala M, Isacson O. Cell therapy and stem cells in animal models of motor neuron disorders. Eur J Neurosci. 2007;26:1721–1737. doi: 10.1111/j.1460-9568.2007.05780.x. [DOI] [PubMed] [Google Scholar]
  • [19].Ferguson TA, Elman LB. Clinical presentation and diagnosis of amyotrophic lateral sclerosis. NeuroRehabilitation. 2007;22:409–416. [PubMed] [Google Scholar]
  • [20].Kenner M, Menon U, Elliott DG. Multiple sclerosis as a painful disease. Int Rev Neurobiol. 2007;79:303–321. doi: 10.1016/S0074-7742(07)79013-X. [DOI] [PubMed] [Google Scholar]
  • [21].Baron EM, Young WF. Cervical spondylotic myelopathy: a brief review of its pathophysiology, clinical course, and diagnosis. Neurosurgery. 2007;60:S35–41. doi: 10.1227/01.NEU.0000215383.64386.82. [DOI] [PubMed] [Google Scholar]
  • [22].Schnell SA, Staines WA, Wessendorf MW. Reduction of lipofuscin-like autofluorescence in fluorescently labeled tissue. J Histochem Cytochem. 1999;47:719–730. doi: 10.1177/002215549904700601. [DOI] [PubMed] [Google Scholar]
  • [23].Barden H. Interference filter microfluorometry of neuromelanin and lipofuscin in human brain. J Neuropathol Exp Neurol. 1980;39:598–605. doi: 10.1097/00005072-198009000-00008. [DOI] [PubMed] [Google Scholar]
  • [24].Brizzee KR, Ordy JM, Kaack B. Early appearance and regional differences in intraneuronal and extraneuronal lipofuscin accumulation with age in the brain of a nonhuman primate (Macaca mulatta) J Gerontol. 1974;29:366–381. doi: 10.1093/geronj/29.4.366. [DOI] [PubMed] [Google Scholar]
  • [25].Correa FM, Innis RB, Rouot B, Pasternak GW, Snyder SH. Fluorescent probes of alpha- and beta-adrenergic and opiate receptors: biochemical and histochemical evaluation. Neurosci Lett. 1980;16:47–53. doi: 10.1016/0304-3940(80)90099-3. [DOI] [PubMed] [Google Scholar]
  • [26].Billinton N, Knight AW. Seeing the wood through the trees: a review of techniques for distinguishing green fluorescent protein from endogenous autofluorescence. Anal Biochem. 2001;291:175–197. doi: 10.1006/abio.2000.5006. [DOI] [PubMed] [Google Scholar]
  • [27].Lo YM, Patel P, Wainscoat JS, Sampietro M, Gillmer MD, Fleming KA. Prenatal sex determination by DNA amplification from maternal peripheral blood. Lancet. 1989;2:1363–1365. doi: 10.1016/S0140-6736(89)91969-7. [DOI] [PubMed] [Google Scholar]
  • [28].Herzenberg LA, Bianchi DW, Schroder J, Cann HM, Iverson GM. Fetal cells in the blood of pregnant women: detection and enrichment by fluorescence-activated cell sorting. Proc Natl Acad Sci U S A. 1979;76:1453–1455. doi: 10.1073/pnas.76.3.1453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [29].Thomas MR, Williamson R, Craft I, Yazdani N, Rodeck CH. Y chromosome sequence DNA amplified from peripheral blood of women in early pregnancy. Lancet. 1994;343:413–414. doi: 10.1016/S0140-6736(94)91248-3. [DOI] [PubMed] [Google Scholar]
  • [30].Johnson KL, Zhen DK, Bianchi DW. The use of fluorescence in situ hybridization (FISH) on paraffin-embedded tissue sections for the study of microchimerism. Biotechniques. 2000;29:1220–1224. doi: 10.2144/00296st01. [DOI] [PubMed] [Google Scholar]
  • [31].van Dijk BA, Boomsma DI, de Man AJ. Blood group chimerism in human multiple births is not rare. Am J Med Genet. 1996;61:264–268. doi: 10.1002/(SICI)1096-8628(19960122)61:3<264::AID-AJMG11>3.0.CO;2-R. [DOI] [PubMed] [Google Scholar]
  • [32].Khosrotehrani K, Wataganara T, Bianchi DW, Johnson KL. Fetal cell-free DNA circulates in the plasma of pregnant mice: relevance for animal models of fetomaternal trafficking. Hum Reprod. 2004;19:2460–2464. doi: 10.1093/humrep/deh445. [DOI] [PubMed] [Google Scholar]
  • [33].Khosrotehrani K, Reyes RR, Johnson KL, Freeman RB, Salomon RN, Peter I, et al. Fetal cells participate over time in the response to specific types of murine maternal hepatic injury. Hum Reprod. 2007;22:654–661. doi: 10.1093/humrep/del426. [DOI] [PubMed] [Google Scholar]

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