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
Short Bio – Ina Stelzer
Dr. Ina Stelzer is a molecular biologist and systems immunologist (PhD) specializing in understanding how the maternal immune system adapts to pregnancy. She is currently an Assistant Professor at the University of California San Diego and the Director of Reproductive Immunology at the Center for Perinatal Discovery. Her research integrates human immunology and animal models to study individual immune cells and the maternal nervous system in healthy and complicated pregnancies. Identifying determinants of the uterus-brain axis ultimately aims to improve maternal and child health through innovative applications of high-dimensional proteomics, targeted neuromodulation, and multi-omic modeling. Previously, she held research positions at Stanford University, Cincinnati Children’s Hospital, and the University of Hamburg, Germany, with key contributions published in Science Translational Medicine, Nature Communications, and Nature Reviews Immunology. She earned her Ph.D. in Human Biology (summa cum laude) and is a recipient of academic awards.
Characterization of human amniotic fluid stem cells and their potential role in maternal microchimerism
Bernadette L. Bramreiter
Bernadette L. Bramreiter1, Katja Sallinger1, Emiel Slaats1, Julia Schönberger1, Katharina Schuch1, Philipp Klaritsch², Herbert Fluhr², Thomas Kroneis1
1Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria
2Department of Obstetrics and Gynaecology, Medical University of Graz, Graz, Austria
Objective
Microchimerism (MC) is defined as the presence of a small population of genetically distinct cells within a host. During pregnancy, bidirectional cell trafficking across the feto-maternal interface results in maternal and fetal microchimerism. Since microchimeric cells represent cell types derived from all three germ layers, we assume cells with stem cell-like properties to be responsible for the establishment of lifelong MC. However, the cellular routes and mechanisms remain unclear. We hypothesize that maternal cells reach the fetus via ingestion of fetally-derived amniotic fluid (AF) and subsequent transmigration into fetal tissues, potentially through the gastrointestinal tract, and that these cells represent a subpopulation of amniotic fluid stem cells (AFSCs).
Methods
Stem cells were isolated from AF using CD117-targeting microbeads and characterized using a 16-marker multicolor flow cytometry panel designed to identify AFSCs and distinguish them from other progenitor and contaminating populations. Markers included CD27, CD34, CD44, CD45, CD73, CD90, CD105, CD117, HLA-ABC, HLA-DR, SSEA-3, SSEA-4, Tra-1-60, Tra-1-81, and OCT3/4. Pluripotency was assessed by trilineage differentiation into early germ layer intermediates. Potential maternal microchimeric cells were identified in male pregnancies using XIST and RPS4Y1-specific padlock probes and/or X Y-FISH.
Results
AFSCs expressed pluripotency-associated markers, including OCT3/4 and CD117, and lacked lineage-specific markers such as CD34 and CD45. Upon differentiation, AFSCs generated early germ layer intermediates expressing lineage specific morphology and markers such as FOXA2 (endoderm), CD144 (mesoderm), and Nestin (ectoderm). Maternal cells were detected in three of four AFSC samples.
Conclusion
The presence of maternal cells within the AFSC compartment supports a potential role for feto-maternal cell trafficking in the AF and suggests AFSCs as a potential source of maternal microchimeric cells.