Distinct effects of short- and long-term type 1 diabetes to the placental extracellular matrix and fetal development in mice

Sanches, Juliane Cristina Trevisan; Favaro, Rodolfo R.; Barrence, Fernanda C; Bevilacqua, Estela; Fortes, Zuleica Bruno; Zorn, Telma Maria Tenório

doi:10.1016/j.placenta.2017.03.005

Cited by 6 publications

(1 citation statement)

References 37 publications

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“…We previously showed in our growth-restricted reduced uteroplacental perfusion pressure (RUPP) mouse placenta study (an animal model of preeclampsia) that collagen was reduced in the RUPP placentae [ 10 ], and in a separate study that maternal exposure to Δ9-THC during pregnancy alters the placental fetal blood spaces and vessel-associated expression of collagen IV [ 11 ]. A mouse study looking at the long- and short-term effects of placental ECM and fetal development identified modification to the synthesis and turnover of ECM before the changes in placental weight [ 73 ]. Furthermore, a study of secreted human placental proteins revealed that those uniquely altered in gestational diabetes mellitus are involved in ECM organization while those altered in intrauterine growth restriction affect collagen and laminin formation [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

Extracellular Matrix Influences Gene Expression and Differentiation of Mouse Trophoblast Stem Cells

Natale

Kotadia

Gustin

et al. 2023

Stem Cells and Development

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Trophoblast stem (TS) cells were first isolated from the mouse placenta; however, little is known about their maintenance and niche in vivo. TS cells, like other stem cells, have a unique microenvironment in which the extracellular matrix (ECM) is a component. Placental pathology is associated with ECM change. However, how these changes and the individual ECM components impact the maintenance or differentiation of TS cells has not been established. This study identified which ECM component(s) maintain the greatest expression of markers associated with undifferentiated mouse trophoblast stem (mTS) cells and which alter the profile of markers of differentiation based on mRNA analysis. mTS cells cultured on individual ECM components and subsequent quantitative polymerase chain reaction analysis revealed that laminin promoted the expression of markers associated with undifferentiated TS cells, fibronectin promoted gene expression associated with syncytiotrophoblast (SynT) layer II cells, and collagen IV promoted the expression of genes associated with differentiated trophoblast. To investigate whether pathological placental ECM influenced the expression of genes associated with different trophoblast subtypes, the mouse model of streptozotocin (STZ)-induced pancreatic β cell ablation and diabetes was used. Female mice administered STZ (blood glucose ≥300 mg/dL) or control (blood glucose ≤150 mg/dL) were mated. Placental pathology at embryonic day (E)14.5 was confirmed with reduced fetal blood space area, reduced expression of the pericyte marker αSMA, and decreased expression of ECM proteins. mTS cells cultured on ECM isolated from STZ placenta were associated with reduced expression of undifferentiated mTS markers and increased expression of genes associated with terminally differentiated trophoblast [ Gcm-1 and SynA (SynT) and junctional zone Tpbpa and Prl2c2 ]. Altogether, these results support the value of using ECM isolated from the placenta as a tool for understanding trophoblast contribution to placental pathology.

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