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Hum. Reprod. Advance Access published online on October 30, 2006
Human Reproduction, doi:10.1093/humrep/del426
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received May 17, 2006
Revised September 26, 2006
Accepted October 2, 2006

Article

Fetal cells participate over time in the response to specific types of murine maternal hepatic injury

K. Khosrotehrani 1 *, R.R. Reyes 2 *, K.L. Johnson 2, R.B. Freeman 3, R.N. Salomon 4, I. Peter 5, H. Stroh 2, S. Guégan 1, and D.W. Bianchi 2 *

1 Division of Genetics, Departments of Pediatrics and Obstetrics and Gynecology, Tufts-New England Medical Center, Boston, MA, USA; Laboratoire de Physiopathologie du Développement, Université Pierre et Marie Curie-Paris VI, Paris, France
2 Division of Genetics, Departments of Pediatrics and Obstetrics and Gynecology, Tufts-New England Medical Center, Boston, MA, USA
3 Department of Surgery, Tufts-New England Medical Center, Boston, MA, USA
4 Department of Pathology, Tufts-New England Medical Center, Boston, MA, USA
5 Institute for Clinical Research and Health Policy Studies, Tufts-New England Medical Center, Boston, MA, USA

* To whom correspondence should be addressed.
D.W. Bianchi, E-mail: dbianchi{at}tufts-nemc.org


  Abstract

BACKGROUND: In humans, fetal microchimeric cells transferred to maternal tissues during pregnancy can adopt a hepatocyte phenotype. Our objective was to determine whether fetal cells participate in the response to specific murine post-partum hepatic injuries. METHODS: Wild-type female mice were bred to males transgenic for the enhanced green fluorescent protein (GFP) (n = 42). Following delivery, we created models of chemical or surgical injury with carbon tetrachloride (CCl4) injection or by performing partial hepatectomy. Liver injury was assessed histologically. Fetal cells in maternal liver were detected and measured by real-time PCR amplification of the gfp transgene and by immunofluorescence using anti-GFP antibodies. RESULTS: PCR results showed that in chemical but not surgical injury, fetal GFP+ cells were detectable in maternal liver and spleen and that fetal cell presence was significantly increased over time following injury (4 versus 8 weeks, P = 0.006 for liver and P = 0.0006 for spleen). In some animals, following chemical injury, GFP+ cells were detected by immunofluorescence. CONCLUSIONS: The results of this preliminary study suggest that specific types of injury may elicit different fetal cell responses in maternal organs. There is a significant effect of time on fetal cell presence in liver and spleen. Furthermore, real-time PCR amplification is more sensitive than immunofluorescence for the detection of microchimeric fetal cells.

Keywords: carbon tetrachloride/fetal cell microchimerism/partial hepatectomy/pregnancy/stem cells.

These authors contributed equally to this work.


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