Biology subjects

Amabebe, E.

Publications and source records attributed to Amabebe, E..

4 recordsLinked to original sources

bioRxiv2026

From Stress to Survival: Trophoblast-Derived Extracellular Vesicle Proteome Captures Aspirin-Driven Cellular Reprogramming in a Preeclampsia Model.

BackgroundLow-dose aspirin (LDA) reduces preeclampsia (PE) risk by up to 40%, yet its molecular effects on chorion trophoblast cells (CTCs) a fetal membrane lineage at the feto-maternal interface remain obscure. CTCs form a structural and immunoregulatory barrier whose dysfunction drives inflammation-associated membrane pathology in PE. Extracellular vesicles (EVs) released by CTCs may encode cellular stress and adaptation states, offering a molecular window into aspirins timing-dependent effects on PE risk modification. MethodsHuman CTCs were challenged with cigarette smoke extract (CSE) to model oxidative stress-driven PE pathology. Two paradigms were tested: (1) prophylactic aspirin (4 and 40 {micro}g/ml) before and/or flanking CSE, and (2) therapeutic aspirin after CSE challenge. EVs were isolated via ultracentrifugation and size exclusion chromatography, characterized by nanoparticle tracking and immunoblotting, and profiled by quantitative mass spectrometry. Network pathway analysis and machine-learning biomarker selection defined EV-encoded molecular states. ResultsCTC-derived EVs from CSE-exposed cells carried a PE-like proteomic signature marked by suppressed VEGF/ECM remodeling, activated TNF-p53 apoptotic signaling, and heightened inflammation. Prophylactic low-dose aspirin shifted EV cargo toward preserved angiogenic capacity (VEGFA, COL1A1, MMP14) with attenuated apoptotic and NF-{kappa}B signatures. High-dose aspirin produced broad transcriptional suppression without vascular benefit in EVs. Therapeutic aspirin partially rescued injury-associated EV cargo but failed to restore angiogenic signatures. Machine-learning analysis of EV proteomes identified a prophylactic biomarker panel anchored by HSPA8, SERPINF2, COL4A1, and PLOD1, linked to angiogenic recovery and redox balance. ConclusionsCTC-derived EV proteomic signatures capture dose-and timing-dependent aspirin effects, positioning the chorion as a pharmacological "secondary responder" favoring cellular resilience over classical anti-inflammatory suppression. EV-based molecular profiling might offer a framework for stratifying aspirin responders from non-responders toward personalized PE prevention.

cell biology↗

bioRxiv2026

P-glycoprotein exofection between fetal and maternal cells as a mechanism of intercellular material transfer at the feto maternal interface

Cells can recover lost protein functions through a process we term exofection, in which extracellular vesicles deliver functional molecular cargo to recipient cells and transiently reprogram their activity. Here we show that exosomes derived from fetal chorion trophoblast cells (CTCs) restore P-glycoprotein (P-gp) efflux transporter function in inflammation-impaired maternal decidual cells (DECs) at the feto-maternal interface. CTCs maintain high P-gp expression under inflammatory stress, whereas DECs exhibit marked downregulation of transporter genes and proteins. Proteomic analysis revealed that CTC-derived exosomes package P-gp as a stable cargo that enters DECs through clathrin- and heparan sulfate-dependent uptake pathways. Delivery of CTC exosomes reinstated P-gp abundance and efflux capacity in LPS-stimulated or P-gp-deficient DECs, as shown by calcein efflux and immunofluorescence assays. In pregnant P-gp knockout mice, exosome treatment restored systemic clearance of the P-gp substrate tacrolimus and improved pharmacokinetic parameters. These findings establish exofection as a naturally occurring mechanism of transporter rescue at the feto-maternal interface, where fetal exosomes compensate for inflammation-induced maternal loss of efflux capacity. By restoring P-gp-mediated barrier function, exofection provides a protective strategy that limits the accumulation of xenobiotics and cytokines in maternal tissues and safeguards the fetus. This work reveals a previously unrecognized form of intercellular communication with broad implications for fetal protection, placental biology, cellular engineering, and the delivery of therapeutic proteins. One Sentence SummaryExofection is identified as a novel mechanism of transient cellular engineering via exosome-mediated functional protein delivery between cells.

developmental biology↗

bioRxiv2025

Distinct Virome and Bacteriome Profiles of Term and Preterm Placentas from African, Asian and European Women

While the human placental microbiome has been extensively studied, information regarding the virome remains limited. The association between subclinical placental viral infections and spontaneous preterm birth (PTB) is poorly understood. Hence, we examined fresh placenta samples from women in the UK, Bangladesh, and South Africa to elucidate the virome profiles and association with spontaneous PTB. We employed shotgun metagenomics, real-time PCR, and Gram staining, complemented by bioinformatics, to detect both viruses and bacteria in the decidua and chorionic villous tissues. We did not identify any known pathogenic viruses in 236 placental samples, except for one preterm placenta from the Bangladeshi cohort, where human herpesvirus 6 was detected. The majority of the viruses were bacteriophages present at very low abundance and low frequencies across the three cohorts. Lambdavirus lambda was detected in 14% of UK and 11% of Bangladeshi samples but was absent in South African samples. Papiine betaherpesvirus 3 was identified in 62.5% of South African placentas. Punavirus (29.1%) and Streptococcus phages (16.67%) were also prevalent in South African samples. A variety of bacterial species including Moraxella osloensis, Delftia lacustris, Cutibacterium acnes, Escherichia coli and Staphylococcus epidermidis were detected in samples across the three cohorts in variable frequencies but without any notable tissue immune responses. None of the viruses or bacteria exhibited associations with PTB, except D. lacustris, which was significantly more abundant in preterm compared to term placentas in the Bangladeshi cohort. We conclude that the human placenta harbours a virome predominated by bacteriophages and that subclinical viral infection in spontaneous PTB is rare.

microbiology↗

bioRxiv2020

Differential vaginal Lactobacillus species metabolism of glucose, L and D-lactate by 13C-nuclear magnetic resonance spectroscopy

IntroductionCervicovaginal dysbiosis can lead to infection-associated spontaneous preterm birth. ObjectiveTo determine whether vaginal Lactobacillus species, L. crispatus and L. jensenii, differentially metabolise glucose, L- and/or D-lactate to propagate their survival/dominance. MethodsBacteria were incubated anaerobically for 24h at 37{degrees}C, with 13Cu-glucose, 13C3-D-lactate or 13C3-L-lactate (singularly or combined) for 24h. 13C-spectra were acquired using a 9.4T NMR spectrometer. ResultsL. crispatus and L. jensenii (n=6 each) metabolised 13C-glucose to 13C-lactate and 13C-acetate. L. jensenii converted more 13C3-D- or 13C3-L-lactate to 13C-acetate than L. crispatus, p<0.001. ConclusionConversion of glucose and lactate to acetate by L. jensenii compared to L. crispatus, suggests a possibly important pathomechanism of dysbiosis and infection-associated spontaneous preterm birth.

microbiology↗