Biology subjects

Vaiman, D.

Publications and source records attributed to Vaiman, D..

3 recordsLinked to original sources

bioRxiv2026

Persistent cerebrovascular injury after preeclampsia in the STOX1A mouse model: implications for prokineticin signaling

Preeclampsia (PE) is a pregnancy-related hypertensive disorder associated with neurological complications that may persist beyond pregnancy. Prokineticins (PROK1 and PROK2) and their receptors (PROKR1 and PROKR2) regulate angiogenesis and inflammation and may be involved to PE-associated cerebrovascular injury. This study investigated alterations of the maternal brain prokineticin system during PE and 8 months postpartum, and assessed the consequences of prokineticin receptor inhibition using the PROKR antagonist PC1. Female WT FVB/N mice mated with transgenic males overexpressing STOX1A were used as a model of PE and received PC1 or vehicle during gestation. Circulating and regional brain PROK levels and receptor expression were assessed by ELISA and Western blotting. Long-term cerebral abnormalities were evaluated using high-resolution MRI and GFAP immunostaining. PE mice exhibited hypertension, proteinuria, reduced placental efficiency, and elevated circulating PROK1 and PROK2 levels. PC1 prevented hypertension and attenuated the elevation of circulating PROKs but did not prevent proteinuria or reduced placental efficiency. During PE, hippocampal PROK1 increased while PROK2 decreased; these changes persisted despite treatment. At 7 months postpartum, both PROKs were elevated in the cortex, and these increases were prevented by PC1. Region-specific changes in PROKR1 immunoreactivity and PROKR2 expression showed variable responses to treatment. MRI revealed hippocampal and parieto-temporal T2* hypointensities compatible with microhemorrhagic injury, post-contrast T1 abnormalities supporting blood-brain barrier disruption, and a distinct caudoputamen T1-hyperintense lesion potentially representing a nonhemorrhagic component. PC1 prevented focal cerebral lesions and associated astrocyte reactivity, whereas regional diffusion abnormalities persisted. These findings implicate prokineticin signaling in persistent PE-associated brain injury and support the potential of receptor antagonism to limit selected cerebral alterations.

neuroscience↗

bioRxiv2026

Topological dependent modifications of gene expression in the preeclamptic placenta under aspirin treatment.

Preeclampsia is a hypertensive disorder of pregnancy characterized by systemic endothelial dysfunction and placental inflammatory activation. Low dose aspirin reduces preeclampsia incidence when initiated early, yet its molecular effects on the diseased human placenta remain poorly defined. We performed a topologically resolved transcriptomic analysis of placentas from two independent cohorts of preeclamptic women treated or not with aspirin. Placental samples were obtained either from the villous surface (syncytiotrophoblast rich) or from deep parenchymal regions (stromal and endothelial rich). In villous samples, microarray profiling identified 1,836 differentially expressed genes, predominantly down regulated. Gene set enrichment demonstrated marked suppression of pathways central to hypertensive placental pathology, including TNF/NF {kappa}B signaling, hypoxia responsive programs, glycolysis, and estrogen response cascades. RNA seq analysis of parenchymal samples identified 645 differentially expressed genes, again dominated by down regulation of cell cycle progression, mTORC1 signaling, inflammatory pathways, and metabolic stress responses. Across cohorts, 116 genes were consistently down regulated by aspirin and enriched for hypoxia, NF {kappa}B, estrogen response, and inflammatory signatures. Promoter analysis implicated transcription factors central to vascular inflammation and stress signaling, including NF {kappa}B1, RELA, HIF1A, PPARG, and PARP1. Functional validation in BeWo trophoblasts confirmed aspirin dependent modulation of key placental transcripts and altered secretion of MMP9, ANGPT2, and soluble endoglin (sENG) molecules directly implicated in endothelial dysfunction and hypertensive disease. These findings demonstrate that aspirin attenuates core inflammatory, hypoxic, and metabolic pathways across multiple placental lineages in preeclampsia, providing a mechanistic framework linking early aspirin administration to improved vascular and placental adaptation in hypertensive pregnancy. The action of aspirin upon differentiation of trophoblasts contribute to explain why aspirin protects only when administered early in pregnancy, before the end of the first trimester.

molecular biology↗

bioRxiv2019

Maternal exposure to cigarette smoking induces immediate and durable changes in placental DNA methylation affecting enhancer and imprinting control regions

ObjectiveExposure to cigarette smoking during pregnancy has been robustly associated with cord blood DNA methylation. However, little is known about such effects on the placenta; in particular, whether cigarette smoking before pregnancy could also induce epigenetic alterations in the placenta of former smokers is unknown. Design and resultsPlacental DNA methylation levels were measured in 568 women and compared among non-smokers and women either smoking during their pregnancy or who had ceased smoking before pregnancy. An Epigenome Wide Association Study identified 344 Differentially Methylated Regions (DMRs) significantly associated with maternal smoking status. Among these 344 DMRs, 262 showed "reversible" alterations of DNA methylation, only present in the placenta of current smokers, whereas 44 were also found altered in former smokers, whose placenta had not been exposed directly to cigarette smoking. This observation was further supported by a significant demethylation of LINE-1 sequences in the placentas of both current (-0.43 (-0.83 to -0.02)) and former smokers (-0.55 (-1.02 to -0.08)) compared to nonsmokers. A comparative analysis of the epigenome landscape based on the ENCODE placenta data demonstrated an enrichment of all 344 DMRs in enhancers histone marks. Additionally, smoking-associated DMRs were found near and/or overlapping with 13 imprinting gene clusters encompassing 18 imprinted genes. ConclusionsDNA methylation patterns alterations were found in 344 genomic regions in the placenta of women smoking during their pregnancy, including 44 DMRs and LINE-1 elements, where methylation changes persisted in former smokers, supporting the hypothesis of an "epigenetic memory" of exposure to cigarette smoking before pregnancy. Enhancers regions, including imprinting control regions were also particularly affected by placenta methylation changes associated to smoking, suggesting a biological basis for the sensitivity of these regions to tobacco exposure and mechanisms by which fetal development could be impacted.

genomics↗