Humoral pregnancy analyses reveal strategies for fetal protection and aberrancy in miscarriage [3]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE314502 | GEO | 2026/07/11
REPOSITORIES: GEO
Similar Datasets
Project description:The maternal immune system must simultaneously defend against pathogens with 25 tolerance of the antigenically distinct fetus. Despite the central importance of immune modulation during pregnancy, epitope-level analyses of the maternal antibody repertoire remain lacking. Here, we performed high-throughput, multi-isotype longitudinal serology of 119 women from preconception through pregnancy, combining phage display of linear peptides with whole protein-based antigen assays to profile antibody responses to viral and self-antigens. We observed a broad 30 expansion of the maternal IgG repertoire and a relative increase in IgA titers, both tracking with pregnancy progression. These changes may augment transplacental and mucosal immunity in the fetus and newborn, respectively. Notably, pregnancies ending in miscarriage exhibited pronounced IgA titer spikes against both viral and self-antigens unrelated to active infection (sensitivity 14/19, 74%, specificity 95%), indicating an underlying immune perturbation may 35 precede pregnancy loss.
2026-07-11 | GSE314486 | GEO
Project description:The maternal immune system must simultaneously defend against pathogens with 25 tolerance of the antigenically distinct fetus. Despite the central importance of immune modulation during pregnancy, epitope-level analyses of the maternal antibody repertoire remain lacking. Here, we performed high-throughput, multi-isotype longitudinal serology of 119 women from preconception through pregnancy, combining phage display of linear peptides with whole protein-based antigen assays to profile antibody responses to viral and self-antigens. We observed a broad 30 expansion of the maternal IgG repertoire and a relative increase in IgA titers, both tracking with pregnancy progression. These changes may augment transplacental and mucosal immunity in the fetus and newborn, respectively. Notably, pregnancies ending in miscarriage exhibited pronounced IgA titer spikes against both viral and self-antigens unrelated to active infection (sensitivity 14/19, 74%, specificity 95%), indicating an underlying immune perturbation may 35 precede pregnancy loss.
2026-07-11 | GSE314491 | GEO
Project description:Transplacental immune programming refers to the concept that during pregnancy, significant crosstalk occurs between the maternal and fetal immune system, with consequent long‐term effects especially for the offspring. In this study, we searched for evidence of transplacental programming in cellular immunity. We made the surprising observation that there is a stringent and specific correlation of regulatory T cells (Treg) between the mother and the fetus. Gene microarray analysis indicates that interleukin 10 (IL‐10) might be involved in transplacental Treg alignment. This is further supported by the direct correlation of IL‐10 at a protein level between maternal fetal dyads. In vitro data provide evidence that IL‐10 may regulate the homeostatic balance between Tregs and non‐Tregs through selective upregulation of the anti‐apoptotic molecule Bcl‐2 in Tregs. Induction of IL‐10 might be triggered by fetus‐derived estriol (E3), which readily crosses the placenta and correlates with maternal IL‐ 10 levels. Our study represents the first example of transplacental regulation of cellular immunity between the mother and the fetus. These novel findings might have major implications for pregnancy related‐changes in the maternal and fetal immune system, and provide possible mechanistic insights into how prenatal influences can lead to subsequent immunopathologies, such as allergy and autoimmunity. T-reg and non-Treg samples of non pregnant women, and matched cord blood and maternal blood T-regs and non-T-regs
2013-11-04 | E-GEOD-31976 | biostudies-arrayexpress
Project description:Transplacental immune programming refers to the concept that during pregnancy, significant crosstalk occurs between the maternal and fetal immune system, with consequent long‐term effects especially for the offspring. In this study, we searched for evidence of transplacental programming in cellular immunity. We made the surprising observation that there is a stringent and specific correlation of regulatory T cells (Treg) between the mother and the fetus. Gene microarray analysis indicates that interleukin 10 (IL‐10) might be involved in transplacental Treg alignment. This is further supported by the direct correlation of IL‐10 at a protein level between maternal fetal dyads. In vitro data provide evidence that IL‐10 may regulate the homeostatic balance between Tregs and non‐Tregs through selective upregulation of the anti‐apoptotic molecule Bcl‐2 in Tregs. Induction of IL‐10 might be triggered by fetus‐derived estriol (E3), which readily crosses the placenta and correlates with maternal IL‐ 10 levels. Our study represents the first example of transplacental regulation of cellular immunity between the mother and the fetus. These novel findings might have major implications for pregnancy related‐changes in the maternal and fetal immune system, and provide possible mechanistic insights into how prenatal influences can lead to subsequent immunopathologies, such as allergy and autoimmunity.
2013-11-04 | GSE31976 | GEO
Project description:The initiation of labor and preterm labor is a complex and precise physiological process involving a well-orchestrated dialogue between the mother and fetus. Immunological tolerance toward the semiallogeneic fetus is one of many maternal adaptations required for a successful pregnancy. T lymphocyte are major players of the adaptive immune system and balance tolerance and protection at the maternal-fetal interface. However, the dynamics, repertoire and subset programming of T cells across labor are still poorly understood. Here we integrated single-cell RNA sequencing and single-cell ATAC sequencing analyses of human decidua basalis and decidua parietalis from term and preterm labor to depict the composition of T cells at the maternal-fetal interface during late pregnancy and to investigate the potential mechanisms underlying the occurrence of preterm labor.
2026-05-13 | GSE298153 | GEO
Project description:During pregnancy, immune responses must balance fetal protection from infections with tolerance of the semi-allogeneic fetus. However, the mechanisms regulating maternal-fetal tolerance remain poorly understood. Recently, we identified KIR+CD8+ T cells as a previously underappreciated regulatory subset important for suppressing self-reactivity in human autoimmune and infectious diseases. To better understand what other roles these cells might play, we asked whether they are active during pregnancy. We first observed an increased frequency of KIR+CD8+ T cells in the peripheral blood of pregnant women at the second trimester, especially in those carrying a male fetus. In vitro, KIR+CD8+ T cells inhibited the alloreactive responses of maternal T cells against irradiated cord blood cells and suppressed HY-specific CD8+ T cells from mothers with a male fetus. Therefore, the higher induction of KIR+CD8+ T cells in mothers carrying a male fetus may help suppress additional allogenic responses triggered by Y chromosome antigens. Longitudinal analysis showed that KIR+CD8+ T cells undergo expansion and differentiate into functional cytotoxic cells during pregnancy. Single cell RNA-seq analysis of decidual CD8+ T cells from early pregnancy revealed elevated number and activity of KIR+ CD8+ T cells at the maternal-fetal interface. In addition, increased levels of KIR+CD8+ T cells correlated with pregnancy disorders (e.g., spontaneous abortion and preeclampsia). Taken together, our findings suggest an important role of KIR+CD8+ T cells in the maintenance of maternal tolerance by suppressing fetal-specific alloreactive T cells. They may also be useful as predictive biomarkers or drug targets for human pregnancy disorders.
2025-08-01 | GSE281341 | GEO
Project description:Activation of the maternal immune system during pregnancy can fetal development, which can lead to postnatal susceptibility to a wide range of diseases, including cardiovascular, metabolic and psychiatric disorders. During maternal immune activation (MIA), the maternal body must balance its ressources between mounting an immune response and investing resources into continued metabolism and growth : both essential for survival of the fetus and a successful pregnancy. How the placenta responds to MIA over time and how it can protect the fetus is not well understood, and neither are the fetal consequences of MIA. Here, we characterised the response to an induced acute inflammation in maternal lungs over time across maternal and fetal organs, using a combination of omics-methods, imaging and integrative computational analysis. We found that the placenta, unlike other maternal organs, did not react by inducing a typical inflammatory response, but instead initially induced genes associated to strengthen tissue integrity and simultaneously reduced growth to prevent exposure to potential infections. Afterwards, a return to homeostasis was observed, with heightened biosynthesis and expression of endoplasmic reticulum (ER) stress genes. This mechanism likely protects the fetus from inflammation, as we observed no immune response in the fetal liver transcriptome. Instead, we observed metabolic adaptations in the fetus, including a release of docosahexaenoic acid (DHA) Notably, DHA has a crucial function for fetal brain development , and levels of triglyceride and phosphatidylcholine lipids that are necessary for transportation of DHA to the brain were also increased. This metabolic response is likely a combination of the placental MIA response and temporary maternal fasting, caused by MIA-induced fever and lack of nutrient intake. Our study shows, for the first time, the temporal and systemic response to MIA in lungs across maternal and fetal organs.
2024-06-13 | PXD039402 | Pride
Project description:Immunological tolerance towards the semi-allogeneic fetus is one of many maternal adaptations required for a successful pregnancy. T cells are major players of the adaptive immune system and balance tolerance and protection at the maternal-fetal interface, however, their repertoire and subset programming is still poorly understood. Utilizing emerging scRNA-seq technologies we simultaneously obtained transcript, limited protein, and receptor repertoire at the single-cell level, from decidual and matched maternal peripheral T cells. In agreement with previous work, we find that the decidua maintains a tissue-specific distribution of T cells compared to the periphery. We find that decidual T cells maintain a unique transcriptome programming, characterized by restraint of inflammatory pathways by overexpression of negative regulators. Furthermore, we show little clonal overlap between the decidua and periphery, suggesting minimal ongoing traffic between these scites. Overall, our data demonstrate the power of multi-omic analysis in revealing regulation of fetal-maternal immune co-existence.
2023-04-26 | GSE192558 | GEO
Project description:The transplacental transfer of maternal IgG to the developing fetus is critical for infant protection against infectious pathogens in the first year of life. However, factors that modulate the transplacental transfer efficiency of maternal IgG that could be harnessed for maternal vaccine design remain largely undefined. HIV-infected women have impaired placental IgG transfer, yet the mechanism underlying this impaired transfer is unknown, presenting an opportunity to explore factors that contribute to the efficiency of placental IgG transfer. We measured the transplacental transfer efficiency of maternal HIV and other pathogen-specific IgG in historical U.S. (n=120) and Malawian (n=47) cohorts of HIV-infected mothers and their HIV58 exposed uninfected and HIV-infected infants. We then examined the role of maternal HIV disease progression, infant factors, placental Fc receptor expression, and IgG Fc region subclass and glycan signatures and their association with transplacental transfer efficiency of maternal antigen-specific IgG. We established 3 distinct phenotypes of placental IgG transfer efficiency in HIV-infected women, including: 1) efficient transfer of the majority of antigen-specific IgG populations; 2) generally poor IgG transfer phenotype that was strongly associated with maternal CD4+ T cell counts, hypergammaglobulinemia, and frequently yielded non-protective levels of vaccine-specific IgG; and 3) variable transfer of IgG across distinct antigen specificities. Interestingly, maternal IgG characteristics, such as binding to placentally expressed Fc receptors FcgRIIa and FcgRIIIa, IgG subclass frequency, and Fc region glycan profiles were associated with placental IgG transfer efficiency. These maternal IgG transplacental transfer determinants were distinct among different antigen-specific IgG populations. Our findings suggest that in HIV-infected women, both maternal disease progression and Fc region characteristics modulate the selective placental transfer of distinct IgG subpopulations, with implications for both the health of HIV-exposed uninfected infants and maternal vaccine design.
2019-09-11 | GSE129272 | GEO
Project description:In an attempt to unveil the molecular mechanisms of fetal-maternal interactions during early pregnancy, we have performed the pregnancy induced gene expression analysis in the gravid uteri of fetal cotyledons using the Affymetrix GeneChip Genome Array. In this study, we have performed the microarray analysis of the RNA isolated from fetal cotyledon tissue of Bubalus bubalis on less than 45 day of pregnancy. We have identified total of 8587 differentially expressed genes with significance p ≤ 0.05 in four biological replicates. Bioinformatics analysis of microarray data reveal the cluster of genes involved at the placentome level for various functions such as fetus attachment, transport of nutrition, and immune response. Interestingly, we have identified multiple isoforms of pregnancy associated glycoproteins (PAGs) which were highly up regulated with average fold change of 472.93 in pregnant buffaloes. It was observed the genes responsible for increased immune response were down regulated, suggesting an immune suppressive environment which is required to adapt the semiallogenic fetus for successful pregnancy. We have identified the genes and pathways involved during embryo development and the cluster of genes involved in fetal-maternal interaction, attachment, nourishment of fetus, and immune response. The present study will provide future directions for developing pregnancy diagnosis kit in livestock which is highly necessary for increasing the reproductive efficiency of buffaloes.
2017-12-30 | GSE93874 | GEO