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In humans, naturally acquired microchimerism has been observed in many tissues and organs. Fetal microchimerism, however, has not been investigated in the human brain. Microchimerism of fetal as well as maternal origin has recently been reported in the mouse brain. In this study, we quantified male DNA in the human female brain as a marker for microchimerism of fetal origin (i.e. acquisition of male DNA by a woman while bearing a male fetus). Targeting the Y-chromosome-specific DYS14 gene, we performed real-time quantitative PCR in autopsied brain from women without clinical or pathologic evidence of neurologic disease (n = 26), or women who had Alzheimer’s disease (n = 33). We report that 63% of the females (37 of 59) tested harbored male microchimerism in the brain. Male microchimerism was present in multiple brain regions. Results also suggested lower prevalence (p = 0.03) and concentration (p = 0.06) of male microchimerism in the brains of women with Alzheimer’s disease than the brains of women without neurologic disease. In conclusion, male microchimerism is frequent and widely distributed in the human female brain.

Loading metrics Open Access Peer-reviewed Research Article Male Microchimerism in the Human Female Brain William F. N. Chan , * E-mail: [email protected] Current address: Department of Biochemistry, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada Affiliation Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America ⨯ Cécile Gurnot, Affiliation Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America ⨯ Thomas J. Montine, Affiliation Department of Pathology, University of Washington, Seattle, Washington, United States of America ⨯ Joshua A. Sonnen, Affiliation Department of Pathology, University of Washington, Seattle, Washington, United States of America ⨯ Katherine A. Guthrie, Affiliation Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America ⨯ J. Lee Nelson Affiliations Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America, Division of Rheumatology, University of Washington, Seattle, Washington, United States of America ⨯ Male Microchimerism in the Human Female Brain William F. N. Chan, Cécile Gurnot, Thomas J. Montine, Joshua A. Sonnen, Katherine A. Guthrie, J. Lee Nelson x Published: September 26, 2012 https://doi.org/10.1371/journal.pone.0045592 Article Authors Metrics Comments Media Coverage Reader Comments Figures Figures AbstractIn humans, naturally acquired microchimerism has been observed in many tissues and organs. Fetal microchimerism, however, has not been investigated in the human brain. Microchimerism of fetal as well as maternal origin has recently been reported in the mouse brain. In this study, we quantified male DNA in the human female brain as a marker for microchimerism of fetal origin (i.e. acquisition of male DNA by a woman while bearing a male fetus). Targeting the Y-chromosome-specific DYS14 gene, we performed real-time quantitative PCR in autopsied brain from women without clinical or pathologic evidence of neurologic disease (n = 26), or women who had Alzheimer’s disease (n = 33). We report that 63% of the females (37 of 59) tested harbored male microchimerism in the brain. Male microchimerism was present in multiple brain regions. Results also suggested lower prevalence (p = 0.03) and concentration (p = 0.06) of male microchimerism in the brains of women with Alzheimer’s disease than the brains of women without neurologic disease. In conclusion, male microchimerism is frequent and widely distributed in the human female brain. Citation: Chan WFN, Gurnot C, Montine TJ, Sonnen JA, Guthrie KA, Nelson JL (2012) Male Microchimerism in the Human Female Brain. PLoS ONE 7(9): e45592. https://doi.org/10.1371/journal.pone.0045592Editor: Martin Gerbert Frasch, Université de Montréal, Canada Received: April 30, 2012; Accepted: August 23, 2012; Published: September 26, 2012Copyright: © Chan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Funding: This work was supported by the National Institutes of Health (NS 071418 and AI-41721 to JLN). WFNC was supported by a Canadian Institutes of Health Research Fellowship Award (SIB-95173). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Competing interests: The authors have declared that no competing interests exist. IntroductionDuring pregnancy, genetic material and cells are bi-directionally exchanged between the fetus and mother [1], following which there can be persistence of the foreign cells and/or DNA in the recipient [2], [3]. This naturally acquired microchimerism (Mc) may impart beneficial or adverse effects on human health. Fetal Mc, which describes the persistence of cells and/or DNA of fetal origin in the mother acquired during pregnancy, has been associated with several different autoimmune diseases as well as implicated in tissue repair and immunosurveillance [4]–[6]. Although there is a broad anatomical distribution of Mc in humans that varies in prevalence and quantity [7]–[13], whether the human brain harbors fetal Mc and with what frequency is not known. Fetal Mc has recently been described in the mouse brain [14], [15]. In limited studies, maternal Mc was described in the human fetal brain [9]. In this study, we performed real-time quantitative PCR (qPCR) to detect and quantify male DNA in multiple brain regions of women, targeting the Y-chromosome-specific DYS14 gene sequence as a marker for Mc of fetal origin. Deceased female subjects had no clinical or pathologic evidence of neurologic disease. We also tested brain specimens from women with Alzheimer’s disease (AD) for Mc. This is because AD has been repo...