183 research outputs found

    Forever connected: the lifelong biological consequences of fetomaternal and maternofetal microchimerism

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    BACKGROUND: Originally studied as a mechanism to understand eclampsia-related deaths during pregnancy, fetal cells in maternal blood have more recently garnered attention as a noninvasive source of fetal material for prenatal testing. In the 21st century, however, intact fetal cells have been largely supplanted by circulating cell-free placental DNA for aneuploidy screening. Instead, interest has pivoted to the ways in which fetal cells influence maternal biology. In parallel, an increasing appreciation of the consequences of maternal cells in the developing fetus has occurred.CONTENT: In this review, we highlight the potential clinical applications and functional consequences of the bidirectional trafficking of intact cells between a pregnant woman and her fetus. Fetal cells play a potential role in the pathogenesis of maternal disease and tissue repair. Maternal cells play an essential role in educating the fetal immune system and as a factor in transplant acceptance. Naturally occurring maternal microchimerism is also being explored as a source of hematopoietic stem cells for transplant in fetal hematopoietic disorders.SUMMARY: Future investigations in humans need to include complete pregnancy histories to understand maternal health and transplant success or failure. Animal models are useful to understand the mechanisms underlying fetal wound healing and/or repair associated with maternal injury and inflammation. The lifelong consequences of the exchange of cells between a mother and her child are profound and have many applications in development, health, and disease. This intricate exchange of genetically foreign cells creates a permanent connection that contributes to the survival of both individuals.IP2Immunopathology of vascular and renal diseases and of organ and celltransplantatio

    Breast cancer stroma frequently recruits fetal derived cells during pregnancy

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    Breast carcinomas associated with pregnancy display a high frequency of inflammatory types, multifocal lesions and lymph node metastasis. Because pregnancy results in transfer to mothers of foetal stem cells that can migrate and differentiate into various tissues, we addressed the issue of whether such cells are present in breast carcinoma associated with pregnancy

    Germline variants are associated with increased primary melanoma tumor thickness at diagnosis

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    Germline genetic variants have been identified, which predispose individuals and families to develop melanoma. Tumor thickness is the strongest predictor of outcome for clinically localized primary melanoma patients. We sought to determine whether there is a heritable genetic contribution to variation in tumor thickness. If confirmed, this will justify the search for specific genetic variants influencing tumor thickness. To address this, we estimated the proportion of variation in tumor thickness attributable to genome-wide genetic variation (variant-based heritability) using unrelated patients with measured primary cutaneous melanoma thickness. As a secondary analysis, we conducted a genome-wide association study (GWAS) of tumor thickness. The analyses utilized 10 604 individuals with primary cutaneous melanoma drawn from nine GWAS datasets from eight cohorts recruited from the general population, primary care and melanoma treatment centers. Following quality control and filtering to unrelated individuals with study phenotypes, 8125 patients were used in the primary analysis to test whether tumor thickness is heritable. An expanded set of 8505 individuals (47.6% female) were analyzed for the secondary GWAS meta-analysis. Analyses were adjusted for participant age, sex, cohort and ancestry. We found that 26.6% (SE 11.9%, P = 0.0128) of variation in tumor thickness is attributable to genome-wide genetic variation. While requiring replication, a chromosome 11 locus was associated (P < 5 × 10−8) with tumor thickness. Our work indicates that sufficiently large datasets will enable the discovery of genetic variants associated with greater tumor thickness, and this will lead to the identification of host biological processes influencing melanoma growth and invasion
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