Neha Sharma
Email Address
obgneha@nus.edu.sg
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Publication Persistent human KIT receptor signaling disposes murine placenta to premature differentiation resulting in severely disrupted placental structure and functionality(MDPI AG, 2020) Kaiser, F.; Hartweg, J.; Jansky, S.; Pelusi, N.; Kubaczka, C.; Sharma, N.; Nitsche, D.; Langkabel, J.; Schorle, H.; OBSTETRICS & GYNAECOLOGYActivating mutations in the human KIT receptor is known to drive severe hematopoietic disorders and tumor formation spanning various entities. The most common mutation is the substitution of aspartic acid at position 816 to valine (D816V), rendering the receptor constitutively active independent of ligand binding. As the role of the KIT receptor in placental signaling cascades is poorly understood, we analyzed the impact of KITD816V expression on placental development using a humanized mouse model. Placentas from KITD816V animals present with a grossly changed morphology, displaying a reduction in labyrinth and spongiotrophoblast layer and an increase in the Parietal Trophoblast Giant Cell (P-TGC) layer. Elevated differentiation to P-TGCs was accompanied with reduced differentiation to other Trophoblast Giant Cell (TGC) subtypes and by severe decrease in proliferation. The embryos display growth retardation and die in utero. KITD816V-trophoblast stem cells (TSC) differentiate much faster compared to wild type (WT) controls. In undifferentiated KITD816V-TSCs, levels of Phosphorylated Extracellular-signal Regulated Kinase (P-ERK) and Phosphorylated Protein Kinase B (P-AKT) are comparable to wildtype cultures differentiating for 3–6 days. Accordingly, P-TGC markers Placental Lactogen 1 (PL1) and Proliferin (PLF) are upregulated as well. The results reveal that KIT signaling orchestrates the fine-tuned differentiation of the placenta, with special emphasis on P-TGC differentiation. Appropriate control of KIT receptor action is therefore essential for placental development and nourishment of the embryo. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.Publication A review of the role of inositols in conditions of insulin dysregulation and in uncomplicated and pathological pregnancy(Taylor & Francis, 2020-12-07) Oliver Watkins; Hannah Yong; Neha Sharma; Shiao-Yng Chan; OBSTETRICS & GYNAECOLOGYInositols, a group of 6-carbon polyols, are highly bioactive molecules derived from diet and endogenous synthesis. Inositols and their derivatives are involved in glucose and lipid metabolism and participate in insulin-signaling, with perturbations in inositol processing being associated with conditions involving insulin resistance, dysglycemia and dyslipidemia such as polycystic ovary syndrome and diabetes. Pregnancy is similarly characterized by substantial and complex changes in glycemic and lipidomic regulation as part of maternal adaptation and is also associated with physiological alterations in inositol processing. Disruptions in maternal adaptation are postulated to have a critical pathophysiological role in pregnancy complications such as gestational diabetes and pre-eclampsia. Inositol supplementation has shown promise as an intervention for the alleviation of symptoms in conditions of insulin resistance and for gestational diabetes prevention. However, the mechanisms behind these affects are not fully understood. In this review, we explore the role of inositols in conditions of insulin dysregulation and in pregnancy, and identify priority areas for research. We particularly examine the role and function of inositols within the maternal-placental-fetal axis in both uncomplicated and pathological pregnancies. We also discuss how inositols may mediate maternal-placental-fetal cross-talk, and regulate fetal growth and development, and suggest that inositols play a vital role in promoting healthy pregnancy.