Microchimerism in Reproductive Health: From Infertility and Placental Dysfunction to Cardiovascular Risk
Microchimerism intersects with reproductive health and long-term maternal disease risk, linking placental biology, immune regulation, and vascular pathology. Evidence of microchimeric cells in endometrium and menstrual blood has prompted hypotheses that dysregulated maternal–fetal cell trafficking may contribute to infertility and pregnancy loss. Placental dysfunction—central to complications such as preeclampsia and fetal growth restriction—is associated with altered release of inflammatory mediators and increased fetal microchimerism in maternal circulation. Persistence of fetal-origin cells months to years postpartum, correlations with inflammatory proteomic signatures, and variation by fetal sex support a model in which microchimerism participates in sustained immune activation that may influence later cardiovascular risk. Advances in detection technologies, including digital PCR, high-dimensional proteomics, and highly sensitive HLA-specific flow cytometry capable of isolating rare viable maternal cells from fetal stem cell compartments, are refining mechanistic insight into trafficking and retention. This session covers microchimerism as a potential mediator connecting placental stress, reproductive outcomes, and women’s long-term cardiometabolic health.
Thursday, 28.05.2026, Day 2
Time: 14:00 – 15:30
Microchimerism in infertility and pregnancy loss
Henriette Svarre Nielsen
University of Copenhagen, Denmark
This talk will focus on microchimerism in infertility and pregnancy loss. The talk will give an overview of the presence of microchimerism in the endometrium and menstrual blood. The research leading to the hypothesis that microchimerism could play a role in infertility and pregnancy loss will be summarized and studies exploring the hypothesis will be presented.
Women’s risk of cardiovascular disease after pregnancy complications: does a dysfunctional placenta and fetal microchimerism play a role?
Anne Cathrine Staff
University of Oslo and Oslo University Hospital, Oslo, Norway
Several common obstetric complications are associated with increased risk of future maternal cardiovascular disease (CVD). The risk is especially high after severe and repeated pregnancy complications. The mechanisms for the associations are not clear, but likely involve a synergy of preexisting risk factors (for the obstetric adverse outcome and cardiovascular disease) and risk factors mediated by the pregnancy complication. Common to many of these obstetric complications (e.g. preeclampsia and other hypertensive disorders of pregnancy, fetal growth restriction, preterm birth and gestational diabetes mellitus) is that the placenta is dysfunctional.
In preeclampsia, this placental dysfunction is closely linked to cellular syncytiotrophoblast stress, with an ensuing dysregulated release of proinflammatory and antiangiogenic proteins into maternal circulation. Preeclampsia is also associated with increased presence and quantity of long-lived fetal-origin cells in maternal circulation, termed fetal microchimerism. Our studies from human pregnancy have shown that the levels of fetal microchimeric cells in the mother correlates with placental dysfunction, as well as with severe maternal hypertension. Our human data also support a role for fetal-maternal histocompatibility in fetal microchimerism dynamics, both during pregnancy and postpartum.
The presentation will lay out the limited epidemiological background for linking fetal microchimerism to long-term maternal CVD. It will discuss how fetal microchimerism could potentially drive vascular inflammation in women and thereby contribute to premature maternal cardiovascular disease. Future and ongoing projects to improve the understanding of the role of fetal microchimerism in female cardiovascular health will be discussed.
Fetal Microchimeric Cell Retention Following Preeclampsia
Ina A. Stelzer
Ina A. Stelzer1,2, Joshua Gillard1, Maximilian Sabayev1, Agnes Wieczorek3, Dorien Feyaerts1, Oshra Sedan4, Petra C. Arck3, Brice Gaudilliere1, Mark Hlatky4*, Virginia D. Winn5*
1Department of Anesthesia, Stanford University, CA, USA
2Department of Pathology, University of California San Diego, CA, USA
3Department of Obstetrics and Prenatal Medicine, University Medical Center Hamburg-Eppendorf, Germany
4Department of Medicine and of Health Research and Policy, Stanford University, CA, USA
5Department of Obstetrics and Gynecology, Stanford University, CA, USA
*co-senior authors
Introduction: Fetal microchimerism (FMc), the acquisition and long-term persistence of intact fetal cells in the mother, is increased in the blood of pregnancies with preeclampsia (PE) and may affect immune function and contribute to the higher risk of developing cardiovascular diseases after PE. The aim of this study was to measure levels of FMc in the postpartum period in participants with and without PE, and to examine the association of FMc with the plasma proteome.
Methods: To screen for FMc in maternal blood, we performed PCR in paired cord- and maternal-blood derived DNA to identify deletion-insertion polymorphisms (DIP) that were present only in the fetal DNA (i.e., informative DIPs). After informed consent, we applied digital droplet PCR to maternal postpartum PBMC-derived DNA from 8 subjects with PE (incl. 2 twin pregnancies) and 11 with normotensive pregnancies, and screened for informative DIPs. FMc was quantified as genomic equivalents (fetal cells, gEq) per 1×106 maternal cells, and compared between groups using Mann-Whitney test. We analyzed the maternal postpartum plasma proteome for 7,000 proteins using an aptamer-based platform (SomaLogic), and performed gene set enrichment on the proteins most highly correlated with FMc levels.
Results: FMc cells were detectable in 79% (15/19) of samples up to three years after delivery. There was no significant difference in FMc levels between those with a history of PE compared to controls in this small sample, or according to gravida or maternal age. Interestingly, FMc levels were significantly lower in subjects who had been pregnant with a female fetus (n=11) than with a male fetus (n=10): mean 40 vs. 111 gEq/1×106 maternal cells, p=0.02. This difference appeared to be more pronounced in subjects with a history of PE, but there were relatively few such subjects. Higher FMc levels were significantly associated with higher levels of inflammatory plasma proteins, including toll-like-receptor pathway-associated proteins, and the enriched gene sets ‘TLR7/8 Cascade’, ‘MyD88’, ‘TLR2 Cascade’.
Conclusion: In this pilot study, FMc cells were retained in maternal blood for months to years post-delivery, and FMc levels varied according to fetal sex. FMc levels were positively correlated with an inflammatory proteomic plasma environment. Maternal immune profiles of this and follow-up cohorts will determine whether PE-associated immune dysregulation persists postpartum alongside FMc levels.
Keywords: Fetal microchimerism, Preeclampsia, Postpartum health
An optimized flow cytometry-based method for the isolation of potential microchimeric maternal cells in human mesenchymal stem cells using monoclonal HLA class I specific antibodies
Bernadette L. Bramreiter
Bernadette L. Bramreiter1, Rachel C. Quilang2, Carin van der Keur2, Anne Wagenmakers2, Katja Sallinger1, Emiel Slaats1, Julia Schönberger1, Katharina Schuch1, Hyun-Dong Chang3,4, Dave Roelen2, Thomas Kroneis1, Michael Eikmans2
1: Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical
University of Graz, Graz, Austria
2: Department of Immunology, Leiden University Medical Center, Leiden, Netherlands
3: German Rheumatism Research Center Berlin (DRFZ), Berlin, Germany
4: Institute for Biotechnology, Technische Universität, Berlin, Germany
Objectives
Microchimerism (MC) is defined as the presence of a small population of genetically distinct cells originating from another individual. During pregnancy, cells are trafficking across the feto-maternal interface in both directions, resulting in maternal and fetal MC (mMC, fMC). Microchimeric cells have been reported to exhibit stem and progenitor cell-like properties, suggesting that stem cell compartments may contribute to MC persistence. However, the identity and trafficking pathways of the cells remain poorly understood. This study aimed to develop and optimize a sex-unbiased flow cytometry-based method to isolate viable potential mMC cells from human fetal mesenchymal stem cell (MSC) populations using monoclonal HLA class I-specific antibodies (HuMoAbs).
Methods
HuMoAbs of IgG and IgM isotypes were generated at LUMC from transformed B lymphocytes. Thirteen HuMoAbs targeting HLA-A and HLA-B (e.g. A3 and B8) were selected and validated for the separation of maternal and fetal cells. To improve population discrimination and detection sensitivity, maternal specific HuMoAbs were separately conjugated to PE or FITC and used simultaneously for staining. PE/FITC double-positive cells were considered of maternal origin.