313. Fetal microchimerism in pregnancy and placental dysfunction

Abstract

Introduction During pregnancy, bidirectional cell trafficking occurs, generating cellular fetal microchimerism (cFMC). cFMC describes fetal cells that enter maternal tissues and blood, potentially persisting for decades. In the long-term, cFMC may be associated with maternal disease risk (e.g. autoimmunity) and protection (e.g. cancer). In pregnancy, circulating cFMC is augmented in preeclampsia. Preeclampsia is characterized by placental dysfunction, but the underlying mechanisms remain elusive. Other disorders associated with placental dysfunction include HELLP, pregnancy induced hypertension, fetal growth restriction, and pregestational or gestational diabetes mellitus (DM). Objective/hypothesis We hypothesize that placental dysfunction in general, not limited to preeclampsia, correlates with augmented cFMC in maternal circulation. Methods Pregnant women were recruited to the Oslo Pregnancy Biobank (2001–2017) at the time of delivery, prior to active labor. We analyzed 28 pregnancy samples (preeclampsia, n = 9, pregestational or gestational DM, n = 7, uncomplicated pregnancies, n = 6). Buffy coat was isolated from maternal peripheral blood and fetal cord blood. To identify fetus-specific polymorphisms, the samples were genotyped by high resolution sequencing of the human leukocyte antigen (HLA) loci DRB1, DQA1, and DQB1. We identified cFMC using validated HLA polymorphism-specific quantitative polymerase chain reaction assays. Results Our preliminary results showed that of 9 preeclampsia samples, 5 (55.6%) were positive for cFMC; of 7 diabetes samples, 4 (57.1%) were positive. In the control group, only 1 of 6 (16.7%) had cFMC. Discussion We conclude that at the time of delivery, women with preeclampsia or DM (pregestational or gestational) may harbor circulating cFMC more frequently than women with uncomplicated pregnancies. One possible explanation is that dysfunctional placentas could be prone to fetal cell-”leakage”. We speculate that circulating cFMC may promote generalized maternal endothelial inflammation contributing to hypertension and proteinuria, immediately and long-term. A larger cohort is required to investigate cFMC in a wider range of pregnancy complications associated with placental dysfunction.