Dataset Information

HCMV infection mitigate the ability of placental EVs to potentiate neurogenesis by altering their miRNA landscape

ABSTRACT: Human cytomegalovirus (HCMV) is the most common virus transmitted in utero and a leading cause of infectious brain malformations and deafness, yet prognosis methods remain unreliable. Although certain central nervous system lesions caused by HCMV are explained, the neuropathogenesis of congenital infection remains poorly understood. The placenta, a key target of HCMV, plays a critical role during infection due to its involvement in maternal-fetal exchanges, particularly via the secretion of extracellular vesicles (EVs). Placental EVs mediate maternal-fetal communication, carrying proteins and RNAs, including microRNAs, that influence placental function, maternal immune tolerance, and viral defense. Our study explored the effects of placental EVs on fetal neural stem cell phenotype, demonstrating that EVs secreted from HCMV-infected placenta alter neurogenesis. Analysis of EV microRNA profiles revealed infection-induced alterations with predicted interference in brain development pathways. These findings highlight the critical role of placental EVs in fetal brain development and their contribution to HCMV neuropathogenesis.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Neuronal Stem Cell

SUBMITTER: Etienne Coyaud

LAB HEAD: Etienne Coyaud

PROVIDER: PXD060921 | Pride | 2026-02-02

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	Raw_files.zip	Other
	report.pg_matrix.tsv	Tabular

Items per page:

1 - 2 of 2

Publications

Placental Extracellular Vesicles Exhibit Reduced Neurogenic Potential Linked to Changes in Their miRNA Landscape Upon HCMV Infection.

Martin Charlène C Martin Hélène H Bergamelli Mathilde M Lobjois Lhorane L Franco Lucie L Bordes Emma E Benchoua Alexandra A Balor Stéphanie S Kantar Diala D Coyaud Etienne E Martins Frédéric F Favereaux Alexandre A Malnou Cécile E CE

Journal of extracellular biology 20260125 1

Extracellular vesicles (EVs) are key mediators of maternal-foetal communication, regulating placental function and foetal development through the transfer of bioactive molecules. Although placental EVs play a crucial role in placental function during pregnancy, their contribution to foetal development, notably foetal brain, remains poorly understood. Human cytomegalovirus (HCMV) is the most common virus transmitted in utero and a leading cause of infectious brain malformations. Although certain ...[more]

PMID: 41589124

Similar Datasets

Project description:The role of extracellular vesicles (EVs), specifically exosomes, in intercellular communication likely plays a key role in placental orchestration of pregnancy and maternal immune sensing of the fetus. While murine models are powerful tools to study pregnancy and maternal-fetal immune interactions, in contrast to human placental exosomes, the content of murine placental and pregnancy exosomes remains largely understudied. Using a recently developed in vitro culture technique, murine trophoblast stem cells derived from B6 mice were differentiated into syncytial-like cells. EVs from the conditioned media, as well as from pregnant and non-pregnant sera, were enriched for exosomes. The RNA composition of these murine trophoblast-derived and pregnancy-associated exosome-enriched-EVs (ExoE-EVs) was determined using RNA-sequencing analysis and expression levels confirmed by qRT-PCR. Differentially abundant miRNAs were detected in syncytial differentiated ExoE-EVs, particularly from the X chromosome cluster (mmu-miR-322-3p, mmu-miR-322-5p, mmu-miR-503-5p, mmu-miR-542-3p, and mmu-miR-450a-5p). These were confirmed to be increased in pregnant mouse sera ExoE-EVs by qRT-PCR analysis. Interestingly, fifteen miRNAs were only present within the pregnancy-derived ExoE-EVs compared to non-pregnant controls. Mmu-miR-292-3p and mmu-miR-183-5p were noted to be some of the most abundant miRNAs in syncytial ExoE-EVs and were also present at higher levels in pregnant versus non-pregnant sera ExoE-EVs. The bioinformatics tool, MultiMir, was employed to query publicly available databases of predicted miRNA-target interactions. This analysis reveals that the X-chromosome miRNAs are predicted to target ubiquitin-mediated proteolysis and intracellular signaling pathways. Knowing the cargo of placental and pregnancy-specific ExoE-EVs as well as the predicted biological targets informs studies using murine models to examine not only maternal-fetal immune interactions but also the physiologic consequences of placental-maternal communication.

Project description:Placental dysplasia critically impairs fetal growth and development by disrupting nutrient supply. Thiamine, predominantly in its bioactive form thiamine pyrophosphate, serves as an essential coenzyme in mitochondrial energy metabolism, yet its regulatory role in placental development remains elusive.ObjectivesThis study systematically unraveled the metabolic network disparities between sows with different reproductive potentials and elucidates the mechanisms by which characterized metabolites enhance placental angiogenesis and nutrient transport efficiency to promote fetal development.MethodsWe initially analyzed plasma and fecal metabolite composition and fecal microbial composition of sows with high and low reproductive potential by 16S rRNA sequencing and untargeted metabolomics. Subsequently, we evaluated the effects of thiamine, the identified characterized metabolite, on the angiogenesis and nutrient transport functions of placenta and the growth and development of offspring in a rat model, as well as verified the effects of thiamine on the cell migration of placental trophoblast cells by in vitro experiment.ResultsSows with high reproductive potential exhibit a distinct metabolic profile with significantly elevated plasma arginine and fecal thiamine levels and the abundance of gut thiamine-synthesizing bacteria increases in parallel. Maternal thiamine supplementation effectively promotes offspring growth and enhances thiamine metabolism in the maternal-placental-fetal axis. Meanwhile, thiamine improves placental function by increasing thiamine-related metabolic enzymes and acetyl-CoA content in the placenta. Furthermore, thiamine facilitates placental angiogenesis via activation of the Notch signaling pathway and initiates the Notch-PI3K/AKT cascade reaction, which regulates placental nutrient metabolism efficiency and transporter expression.ConclusionsMaternal supplementation with thiamine during gestation and lactation promotes placental development and enhances offspring growth through activation of the Notch signaling pathway.