Tissue microchimerism is increased during pregnancy: a human autopsy study

Abstract

Microchimerism is the occurrence of small populations of cells with a different genetic background within an individual. Tissue microchimerism is considered to be primarily pregnancy-derived and is often studied relative to female-dominant autoimmune diseases, pregnancy complications, malignancies, response to injury, and transplantation outcomes. A particular distribution pattern of chimeric cells across various organs was recently described in a model of murine pregnancies. Our aim was to determine the frequency and distribution of tissue microchimerism across organs during and after pregnancy in humans. We performed in situ hybridization of the Y chromosome on paraffin-embedded autopsy samples of kidneys, livers, spleens, lungs, hearts and brains that were collected from 26 women who died while pregnant or within 1 month after delivery of a son. Frequencies of chimeric cells in various tissues were compared with those of a control group of non-pregnant women who had delivered sons. Tissue microchimerism occurred significantly more frequently in the lungs, spleens, livers, kidneys and hearts of pregnant women compared with non-pregnant women (all P < 0.01). We showed that some of the chimeric cells were CD3+ or CD34+. After correction for cell density, the lung was most chimeric (470 Y chromosome-positive nuclei per million nuclei scored), followed by the spleen (208 Y+/10(6) nuclei), liver (192 Y+/10(6) nuclei), kidney (135 Y+/10(6) nuclei), brain (85 Y+/10(6) nuclei) and heart (40 Y+/10(6) nuclei). Data from this unique study group of women who died while pregnant or shortly after delivery provide information about the number and physiologic distribution of chimeric cells in organs of pregnant women. We demonstrate that during pregnancy, a boost of chimeric cells is observed in women, with a distribution across organs, that parallels findings in mouse models.

Biologic mechanisms and clinical consequences of pregnancy alloimmunization

“…[22][23][24][25][26] There are, therefore, multiple potential sources of fetal antigen to prime maternal immune cells, including fetal cells, cell-free DNA, and microvesicles. This degree of invasion gives the placenta and the fetus extraordinary access to maternal physiology.…”

“…While the placenta was traditionally thought to represent a barrier surface between mother and offspring, numerous studies in both mice and humans demonstrate that fetal and/or placental components disseminate widely in the maternal bloodstream and deposit in the maternal tissues. [22][23][24][25][26] There are, therefore, multiple potential sources of fetal antigen to prime maternal immune cells, including fetal cells, cell-free DNA, and microvesicles. [22][23][24][25][26] This semiallogeneic antigen load within the mother has yet to be accurately quantitated but is thought to escalate throughout gestation and become significant by term delivery.…”

“…[22][23][24][25][26] There are, therefore, multiple potential sources of fetal antigen to prime maternal immune cells, including fetal cells, cell-free DNA, and microvesicles. [22][23][24][25][26] This semiallogeneic antigen load within the mother has yet to be accurately quantitated but is thought to escalate throughout gestation and become significant by term delivery. 26,27 Critical experiments from Erlebacher et al have revealed that antigen derived from the fetus is presented in the context of maternal MHC 28 in the secondary lymphoid organs, suggesting that maternal T cells are primed via indirect allorecognition.…”

Immunological implications of pregnancy-induced microchimerism

“…The number of fetal cells in maternal blood progressively increases throughout pregnancy, reaching peak levels of more than 100 fetal cells per mL of maternal blood at parturition 20,21 . Similarly, fetal DNA-containing cells have been found in the cadaveric lung, spleen, liver, kidney and heart tissues of women during pregnancy 8 . Importantly, fetal microchimeric cells are intact cells and represent a completely distinct source of fetal DNA from the placenta-derived, cell-free fetal DNA in the serum of mothers during pregnancy that is increasingly being used for prenatal analysis.…”

“…Beginning early in pregnancy, fetal cells are found in the maternal blood and tissues, with the number of these cells progressively increasing until term 8,9 . Reciprocally, maternal cells are found in human fetal tissues beginning in the second trimester of pregnancy 10,11 .…”