Biology subjects

Cnota, J.

Publications and source records attributed to Cnota, J..

3 recordsLinked to original sources

bioRxiv2026

Plasma Extracellular Vesicle and miRNA Profiles in Pregnancies Complicated by Fetal Congenital Heart Defects

Congenital heart defects (CHDs) are the most common form of fetal malformation however, our understanding of trophoblast health and communication throughout gestation in CHD pregnancies remains limited. The purpose of this study was to assess extracellular vesicles (EVs) and microRNA (miRNA) present in maternal and umbilical cord plasma from a spectrum of CHD subtypes during gestation and at time of delivery. We hypothesized that circulating placenta-derived EVs and miRNA will differ in CHD when compared to controls. Maternal plasma samples were collected between 16-24 weeks of gestation and at the time of delivery. Umbilical cord plasma was obtained following delivery. EVs were isolated from plasma samples using nanoscale flow cytometry, and total EV counts as well as counts by cellular origin were determined. MicroRNA was extracted from maternal plasma and levels quantified using qPCR. Maternal plasma from pregnancies complicated by fetal CHD exhibited higher total EV counts at delivery compared to control. Platelets derived extracellular vesicles (pdEVs) were significantly higher both in maternal and cord blood plasma at the time of delivery in CHD pregnancies compared to gestationally age-matched control pregnancies. Circulating miR22 and miR421 levels were reduced, while miR29c levels were increased in maternal plasma from CHD pregnancies between 16-24 weeks but no differences seen at time of delivery. Pregnancies complicated by CHD are associated with an altered in utero environment by changes in extracellular vesicles and miRNA profile in maternal serum. Circulating EVs and miRNA profiles may therefore serve as minimally invasive indicators of placental and maternal vascular dysfunction in CHD.

cell biology↗

bioRxiv2022

Analysis of commonly expressed genes between first trimester fetal heart and placenta cell types in the context of congenital heart disease

Congenital heart disease (CHD) is often associated with fetal growth abnormalities. During the first trimester of pregnancy, the heart and placenta develop concurrently, and share key developmental pathways. Hence, it is hypothesized that defective morphogenesis of either organ is synergistically linked. However, many studies determined to understand the mechanisms behind CHD overlook the contribution of the placenta. In this study, we aimed to identify commonly expressed genes between first trimester heart and placenta cells using two publicly available single cell sequencing databases. Using a systematic computational approach, we identified 328 commonly expressed genes between heart and placenta endothelial cells and enrichment in pathways including Vasculature Development (GO:0001944, FDR 2.90E-30), and Angiogenesis (GO:0001525, FDR 1.18E-27). We also found, in comparison with fetal heart endothelial cells, 197 commonly expressed genes with placenta extravillous trophoblasts, 128 with cytotrophoblasts and 80 with syncytiotrophoblasts, and included genes such as FLT1, GATA2, ENG and CDH5. Finally, comparison of first trimester cardiomyocytes and placenta cytotrophoblasts revealed 53 commonly expressed genes and enrichment in biological processes integral to cellular function including Cellular Respiration (GO:0045333; FDR 5.05E-08), Ion Transport (GO:0006811; FDR 2.08E-02), and Oxidation-Reduction Process (GO:0055114; FDR 1.58E-07). Overall, our results identify specific genes and cellular pathways common between first trimester fetal heart and placenta cells which if disrupted may concurrently contribute to the developmental perturbations resulting in CHD.

genetics↗

bioRxiv2020

Impaired labyrinth formation prevents the establishment of the maternal-fetal interface in conditional Hand1-deficient mice

IntroductionCongenital heart defects (CHD) affect approximately 1% of all live births, and often require complex surgeries at birth. Placental development and function is vital to ensure normal fetal development. We have previously demonstrated abnormal placental development and vascularization in human CHD placentas, and placental expression changes in genes important for heart development. Hand1 has roles in both heart and placental development and is implicated in CHDs including double right outlet, hypoplastic left heart syndrome, and septal defects; however, Hand1 involvement in placental vascularization and development is under-investigated. We utilized the Hand1A126fs/+ murine model to investigate Hand1 in placentation and vascularization. MethodsHand1A126fs/+ female mice were time-mated with Nkx2.5cre (placenta- and heart-specific) males to produce either Nkx2.5cre;Hand1+/+ or Nkx2.5cre;Hand1A126fs/+ fetuses. Feto-placental units were harvested at timepoints from E8.5 to E14.5 for histological analysis; vascular assessment by immunohistochemistry for Hand1, CD-31, and CK-7; and angiogenesis by qPCR. ResultsEmbryonic lethality occurs in Nkx2.5cre/Hand1A126fs/+ by E14.5 due to a failure of placental labyrinth formation and vascularization. Chorionic trophoblasts did not form, although trophoblast giant cell subtypes were present. Fetal vessels failed to develop properly and were significantly lower in the labyrinth by day E12.5. Placental growth factor levels were significantly increased, and Angiopoietin2 expression trended higher in Nkx2.5cre/Hand1 A126fs/+ placental labyrinths compared to control littermates. ConclusionWe demonstrate that Hand1 expression in placental chorion and trophoblast is necessary for proper patterning of the labyrinth and vascularization within the labyrinth. Multiple angiogenic factors known to be expressed in trophoblast were disrupted in Nkx2.5cre/Hand1 A126fs/+ placental labyrinths compared to control littermates. Alterations in Hand1 expression represent a potential mechanism for abnormal placentation and early miscarriage in cases of CHD.

developmental biology↗