Fetal microchimerism and maternal health: A review and evolutionary analysis of cooperation and conflict beyond the womb

Abstract

Summary The presence of fetal cells has been associated with both positive and negative effects on maternal health. These paradoxical effects may be due to the fact that maternal and offspring fitness interests are aligned in certain domains and conflicting in others, which may have led to the evolution of fetal microchimeric phenotypes that can manipulate maternal tissues. We use cooperation and conflict theory to generate testable predictions about domains in which fetal microchimerism may enhance maternal health and those in which it may be detrimental. This framework suggests that fetal cells may function both to contribute to maternal somatic maintenance (e.g. wound healing) and to manipulate maternal physiology to enhance resource transmission to offspring (e.g., enhancing milk production). In this review, we use an evolutionary framework to make testable predictions about the role of fetal microchimerism in lactation, thyroid function, autoimmune disease, cancer and maternal emotional and psychological health.

Microchimerism: Defining and redefining the prepregnancy context – A review

“…The specific impact of FMc on the mother likely depends on several factors including immunogenetic relationships[1] and specific alleles carried by the Mc [3]. In addition, the role of FMc clearly depends on context, as described in detail by Boddy et al, who used an evolutionary framework to predict FMc function considering the relative cooperative versus conflicting interests of mother and offspring in chronological and tissue-specific contexts [4]. An example of a disease in which FMc appears to be a consistent risk factor is systemic sclerosis [5].…”

Ultrasensitive Detection of Chimerism by Single-Molecule Molecular Inversion Probe Capture and High-Throughput Sequencing of Copy Number Deletion Polymorphisms

“…This approach holds promise for many other applications requiring the sensitive detection of genomically distinct minor cell populations, including fetal microchimerism in autoimmune diseases (1), and solid organ graft injury and transplant rejection (2,3). Future work will seek to establish the utility of smMIP capture in monitoring a variety of disease states, as well as in larger cohorts of HSCT patients as a potential surrogate for MRD detection.…”

“…The detection of genomic chimerism, two or more cell populations from differing genetic origins within an individual, has diverse clinical applications including the detection of fetal microchimerism in autoimmune diseases (1), graft injury and transplant rejection (2,3), and the clinical management of allogeneic hematopoietic stem cell transplantation (HSCT) patients. In HSCT, identification of an increasing proportion of host cells in the transplanted marrow is a harbinger of poor outcomes, potentially indicating the expansion of residual malignant cells and subsequent disease relapse(4–7) or stem cell graft rejection (8).…”

Immunological implications of pregnancy-induced microchimerism

“…These human partner-specific benefits of prior pregnancy correspond in animals to the persistence of fetal-specific maternal T reg cells after parturition, their more rapid secondary expansion after re-stimulation with fetal antigen, and protection against fetal wastage induced by the partial depletion of maternal FOXP3 + CD4 + T cells in secondary compared with primary pregnancy 35 . Thus, the persistence of fetal microchimeric cells expressing pre-existing fetal antigens may represent an altruistic act of first children to promote tolerance in their mothers to genetically similar future siblings 66 , and conflict with genetically discordant siblings 67 .…”

“…There is a provocative association between increased FMC and greater susceptibility of women during their reproductive years to various autoimmune disorders (reviewed in REFS 62,66 ). Most of these studies show increased numbers of fetal microchimeric cells in diseased tissue or the circulation of women with autoimmunity, which suggests that alloreactivity to fetal microchimeric cells or tissue seeding by fetal adaptive immune cells may aggravate or initiate autoimmunity.…”