- https://doi.org/10.1038/s41421-025-00856-3
Maternal acute SARS-CoV-2 infection impairs preimplantation embryo development and reprograms the early offspring hematopoietic system
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Take Notes SARS-CoV-2 infection has raised significant concerns regarding its impact on assisted reproductive technology. We found that oocyte retrieval during acute SARS-CoV-2 infection significantly reduced the rates of good-quality blastocyst formation, but the underlying molecular mechanisms remain poorly understood. To address this, we investigated the effects of maternal acute SARS-CoV-2 infection on preimplantation embryo development and the early offspring hematopoietic system. Using single-cell RNA sequencing (scRNA-seq), we identified developmental delays in morphologically normal blastocysts from infected mothers, characterized by prolonged expression of zygotic genome activation-related genes, downregulation of mTORC1 signaling, and altered energy metabolism, including suppressed oxidative phosphorylation (OXPHOS) and enhanced glycolysis. We further revealed that maternal acute infection induced abnormal methylation/demethylation patterns in preimplantation embryos. To assess the potential long-term impact on offspring, we conducted integrated multi-tissue analyses, including bulk RNA-seq and genome-wide DNA methylation profiling of placental tissues, along with scRNA-seq of umbilical cord blood (UCB) cells from neonates delivered by SARS-CoV-2-infected mothers. Neonates exhibited elevated levels of inflammatory cytokines and an increased abundance of monocytes, indicating an activated myelopoiesis response. In addition, hematopoietic stem and progenitor cells (HSPCs) from UCB showed reduced OXPHOS activity and a skewed differentiation bias toward the myeloid lineage, potentially impacting long-term immune function. Collectively, these findings reveal that maternal acute SARS-CoV-2 infection impairs preimplantation embryo development and leaves a lasting imprint on offspring hematopoietic health through dysregulated energy metabolism, epigenetic modifications, and altered immune responses.
- # Hematopoietic Stem And Progenitor Cells
- # Dysregulated Energy Metabolism
- # Altered Energy Metabolism
- # Preimplantation Embryo Development
- # Assisted Reproductive Technology
- # Altered Immune Responses
- # Single-cell RNA Sequencing
- # Umbilical Cord Blood
- # Expression Of Zygotic Genes
- # Prolonged Expression Of Genes
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BackgroundIn the last decades, human full-term cord blood was extensively investigated as a potential source of hematopoietic stem and progenitor cells (HSPCs). Despite the growing interest of regenerative therapies in preterm neonates, only little is known about the biological function of HSPCs from early preterm neonates under different perinatal conditions. Therefore, we investigated the concentration, the clonogenic capacity and the influence of obstetric/perinatal complications and maternal history on HSPC subsets in preterm and term cord blood.MethodsCD34+ HSPC subsets in UCB of 30 preterm and 30 term infants were evaluated by flow cytometry. Clonogenic assays suitable for detection of the proliferative potential of HSPCs were conducted. Furthermore, we analyzed the clonogenic potential of isolated HSPCs according to the stem cell marker CD133 and aldehyde dehydrogenase (ALDH) activity.ResultsPreterm cord blood contained a significantly higher concentration of circulating CD34+ HSPCs, especially primitive progenitors, than term cord blood. The clonogenic capacity of HSPCs was enhanced in preterm cord blood. Using univariate analysis, the number and clonogenic potential of circulating UCB HSPCs was influenced by gestational age, birth weight and maternal age. Multivariate analysis showed that main factors that significantly influenced the HSPC count were maternal age, gestational age and white blood cell count. Further, only gestational age significantly influenced the clonogenic potential of UCB HSPCs. Finally, isolated CD34+/CD133+, CD34+/CD133– and ALDHhigh HSPC obtained from preterm cord blood showed a significantly higher clonogenic potential compared to term cord blood.ConclusionWe demonstrate that preterm cord blood exhibits a higher HSPC concentration and increased clonogenic capacity compared to term neonates. These data may imply an emerging use of HSPCs in autologous stem cell therapy in preterm neonates.
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Adenylate Kinase 2 Links Energy Metabolism and Cell Fate in Hematopoietic Stem and Progenitor Cells
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