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Fetal-origin cells in maternal circulation correlate with placental dysfunction, fetal sex, and severe hypertension during pregnancy.
- Source :
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Journal of reproductive immunology [J Reprod Immunol] 2024 Mar; Vol. 162, pp. 104206. Date of Electronic Publication: 2024 Jan 20. - Publication Year :
- 2024
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Abstract
- Fetal microchimerism (FMc) arises when fetal cells enter maternal circulation, potentially persisting for decades. Increased FMc is associated with fetal growth restriction, preeclampsia, and anti-angiogenic shift in placenta-associated proteins in diabetic and normotensive term pregnancies. The two-stage model of preeclampsia postulates that placental dysfunction causes such shift in placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFLt-1), triggering maternal vascular inflammation and endothelial dysfunction. We investigated whether anti-angiogenic shift, fetal sex, fetal growth restriction, and severe maternal hypertension correlate with FMc in hypertensive disorders of pregnancy with new-onset features (n = 125). Maternal blood was drawn pre-delivery at > 25 weeks' gestation. FMc was detected by quantitative polymerase chain reaction targeting paternally inherited unique fetal alleles. PlGF and sFlt-1 were measured by immunoassay. We estimated odds ratios (ORs) by logistic regression and detection rate ratios (DRRs) by negative binomial regression. PlGF correlated negatively with FMc quantity (DRR = 0.2, p = 0.005) and female fetal sex correlated positively with FMc prevalence (OR = 5.0, p < 0.001) and quantity (DRR = 4.5, p < 0.001). Fetal growth restriction no longer correlated with increased FMc quantity after adjustment for correlates of placental dysfunction (DRR = 1.5, p = 0.272), whereas severe hypertension remained correlated with both FMc measures (OR = 5.5, p = 0.006; DRR = 6.3, p = 0.001). Our findings suggest that increased FMc is independently associated with both stages of the two-stage preeclampsia model. The association with female fetal sex has implications for microchimerism detection methodology. Future studies should target both male and female-origin FMc and focus on clarifying which placental mechanisms impact fetal cell transfer and how FMc impacts the maternal vasculature.<br />Competing Interests: Declaration of Competing Interest Angiogenic protein reagents (sFlt-1 and PlGF) were donated in-kind to Anne Cathrine Staff by Roche Diagnostics. Some of the microchimerism data have been generated at Chimerocyte Inc., at which Sami B Kanaan is founder. The data were generated in a blinded fashion and Chimerocyte had no role in the final interpretation of the data. The remaining authors report no conflicts of interest.<br /> (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1872-7603
- Volume :
- 162
- Database :
- MEDLINE
- Journal :
- Journal of reproductive immunology
- Publication Type :
- Academic Journal
- Accession number :
- 38309014
- Full Text :
- https://doi.org/10.1016/j.jri.2024.104206