Hum. Reprod. Advance Access originally published online on October 30, 2006
Human Reproduction 2007 22(3):654-661; doi:10.1093/humrep/del426
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Fetal cells participate over time in the response to specific types of murine maternal hepatic injury
1 Division of Genetics, Departments of Pediatrics and Obstetrics and Gynecology, Tufts-New England Medical Center, Boston, MA, USA 2 Laboratoire de Physiopathologie du Développement, Université Pierre et Marie Curie-Paris VI, Paris, France 3 Department of Surgery 4 Department of Pathology and 5 Institute for Clinical Research and Health Policy Studies, Tufts-New England Medical Center, Boston, MA, USA
6 To whom correspondence should be addressed at: Division of Genetics, Department of Pediatrics, Tufts-New England Medical Center, Box 394, 750 Washington Street, Boston, MA 02111, USA. E-mail: dbianchi{at}tufts-nemc.org
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.
Key words: carbon tetrachloride/fetal cell microchimerism/partial hepatectomy/pregnancy/stem cells
Submitted on May 17, 2006; resubmitted on August 2, 2006; resubmitted on September 26, 2006; accepted on October 2, 2006.
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