Fetal microchimerism and women's health: a new paradigm.
ABSTRACT Pregnancy is associated with transfer of maternal cells to the fetus and fetal cells to the mother. In both cases, the transferred cells are described as microchimeric. Fetal microchimeric cells include semi-allogeneic stem cells, which are few in number and are capable of long-term survival in the "foreign" host. They are recognized by the maternal immune system but not rejected or attacked. These cells appear to survive and even thrive for years in a mother's body, perhaps for her lifetime. Previously regarded as potentially dangerous interlopers that might propagate autoimmune and even malignant disease, fetal microchimeric cells are now increasingly being recognized and analyzed for their healing, reparative, and perhaps regenerative roles. Fetal microchimerism (MC) may make significant and previously unknown positive contributions to women's health, longevity, and risk of disease. This article reviews the history, major discoveries, and current concepts and gaps in knowledge in the field of fetal MC.
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ABSTRACT: Effects of parental genotype or parent-offspring genetic interaction are well established in model organisms for a variety of traits. However, these transgenerational genetic models are rarely studied in humans. We have utilized an autism case-control study with 735 mother-child pairs to perform genome-wide screening for maternal genetic effects and maternal-offspring genetic interaction. We used simple models of single locus parent-child interaction and identified suggestive results (P<10(-4)) that cannot be explained by main effects, but no genome-wide significant signals. Some of these maternal and maternal-child associations were in or adjacent to autism candidate genes including: PCDH9, FOXP1, GABRB3, NRXN1, RELN, MACROD2, FHIT, RORA, CNTN4, CNTNAP2, FAM135B, LAMA1, NFIA, NLGN4X, RAPGEF4, and SDK1. We attempted validation of potential autism association under maternal-specific models using maternal-paternal comparison in family-based GWAS datasets. Our results suggest that further study of parental genetic effects and parent-child interaction in autism is warranted.PLoS ONE 10/2013; 8(10):e76978. DOI:10.1371/journal.pone.0076978 · 3.53 Impact Factor
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ABSTRACT: Stroke is a significant unmet clinical need. The current stroke treatment of tissue plasminogen activator is limited to the very acute 4.5 h after disease onset which benefits only less than 3% of ischemic stroke patients. Our overarching hypothesis advances the notion that gender, which has been established as a comorbidity factor of stroke, plays a key role in regenerative medicine, in particular stem cell therapy. We hypothesize that gender is a key factor in culture-induced stemness of adult stem cells. Our goal is to provide new evidence supporting gender effects on stroke and stem cells for the purpose of enhancing our understanding of the pathophysiology of the disease and developing novel stem cell-based therapeutics targeting gender-relevant stress hormones as manifested in a stroke-postpartum depression paradigm.CNS Neuroscience & Therapeutics 10/2014; DOI:10.1111/cns.12339 · 3.78 Impact Factor
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ABSTRACT: Little is known about the recovery of the immune system from normal pregnancy and whether the postpartum period is a uniquely adapted immune state. This report extends previous observations from our group of decreased natural killer (NK) cell cytotoxicity in the postpartum period. NK cytotoxicity was measured from 1 week through 9 months postpartum. In addition, NK cytotoxicity was assayed in the presence or absence of pooled plasmas collected from either postpartum or nonpostpartum women. Samples of cells were stained for inhibitory receptors and analyzed by flow cytometry. NK cytotoxicity remained decreased in postpartum women compared to controls through the first 6 postpartum months, returned to normal levels by 9 months, and remained normal at 12 months. NK cytotoxicity during the first 6 months was further inhibited by the addition of pooled plasma to NK cultures from postpartum women, but the addition of pooled plasma from the control group did not affect that group's NK cultures. There were differences in inhibitory receptor staining between the two groups, with decreased CD158a and CD158b and increased NKG2A expression on postpartum NK cells during the first 3 postpartum months. These data suggest that NK cytotoxicity postpartum inhibition lasts 6 months and is influenced by unidentified postpartum plasma components. The effect may also involve receptors on NK cells.Biological Research for Nursing 08/2013; 16(3). DOI:10.1177/1099800413498927 · 1.34 Impact Factor