Bretelle, F. | Search bioRxiv

bioRxiv2024

Dual specificity phosphate 1 (DUSP1) as a non-invasive circulating biomarker candidate in preeclampsia

BackgroundPreeclampsia (PE) is a multisystem pregnancy complication constituting a major cause of maternal and fetal morbidity and mortality. Factors pointing to a placental origin are the development of the pathology only during pregnancy, and its disappearance in the post-partum period. MethodsHere, we aim to identify new early predictive biomarkers based on a transcriptional signature of PE using RNAseq. Whole blood and serum samples were collected at the time of the first event of PE (V1) and same samples after remote delivery (30-60 postpartum days, V2). These two samples enabled investigation of PE markers found in V1 but absent in V2. To confirm that these candidates are associated with PE, an investigation of associated placental biopsy was also realized (J0). ResultsOur study identified a specific signature of PE including five Gene Ontology clusters including "angiogenesis and differentiation", "cell cycle", "cell adhesion", "inflammatory response" and "cellular metabolism". Interestingly, DUSP1 gene was found specifically modulated in PE. Pregnant women with PE have a higher concentration of DUSP1 in serum compared to healthy donors. Interesting, at a distance from childbirth (V2), DUSP1 finds a rate like the control group showing the predictive interest of DUSP1 as a promising predictive biomarker of PE. ConclusionsThe investigation of DUSP1 in a prospective study with a larger cohort, including the severity aspect of the disease, is necessary to confirm its value as a predictive biomarker in PE.

pathology↗

bioRxiv2024

Normative models combining fetal and postnatal MRI data to characterize neurodevelopmental trajectories during the transition from in- to ex-utero

The perinatal period involves transitioning from an intra- to an extrauterine environment, which requires a complex adaptation of the brain. This period is marked with dynamic and multifaceted cortical changes in both structure and function. Most studies to date have focused either on the fetal or postnatal period, independently. To the best of our knowledge, this is the first neurodevelopmental study targeting the cortical trajectory of typically developing perinatal subjects, combining MRIs from both fetal and postnatal participants. Prior to analysis, preprocessing and segmentation parameters were harmonized across all subjects in order to overcome methodological limitations that arise when studying such different populations. We conducted a normative modeling analysis on a sample of 607 subjects, age ranged 24 to 45 weeks post-conception, to observe changes that arise as participants traverse the birth barrier. We observed that the trajectories of global surface area and several volumetric features, including total gray matter, white matter, brainstem, cerebellum and hippocampi, follow distinct but continuous patterns during this transition. We further report three features presenting a discontinuity in their neurodevelopmental trajectories as participants traverse from a fetal to a postnatal environment: the extra-cerebrospinal fluid volume, the ventricular volume and global gyrification. The current study demonstrates the presence of unique neurodevelopmental patterns for several structural features during the perinatal period, and confirms that not all features are affected in the same way as they cross the birth barrier. SIGNIFICANCE STATEMENTThe perinatal phase comprises the fetal and immediate postnatal period, and is generally described as the time surrounding birth. Comprehensively understanding this period is crucial due to the presence of dynamic and multifaceted brain changes. What makes this investigation unique is that it is the first neurodevelopmental study, to the best of our knowledge, focused on the cortical trajectory of typically developing perinatal subjects through the combination of both fetal and postnatal participants into one analysis. We report that certain brain feature trajectories change drastically as fetuses become newborns, while other features remain continuous. These observations are relevant in both the isolation of biomarkers for later cognitive and physiological disorders and in the understanding of typical cerebral development.

neuroscience↗