Growth impairment, increased placental glucose uptake and altered transplacental transport in VIP deficient pregnancies: Maternal vs. placental contributions
Autor: | Rosanna Ramhorst, Vanesa Hauk, Daniel Paparini, Zaira Naguila, James A. Waschek, Daiana Vota, Fátima Merech, Laura Fernández, Claudia Perez Leiros |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Male medicine.medical_specialty Glucose uptake Placenta Vasoactive intestinal peptide 03 medical and health sciences Mice 0302 clinical medicine Pregnancy Internal medicine medicine Animals Molecular Biology Mice Knockout Fetus Glucose Transporter Type 1 Fetal Growth Retardation biology Chemistry TOR Serine-Threonine Kinases Glucose transporter Placentation Transplacental Biological Transport Trophoblasts Mice Inbred C57BL Pregnancy Complications 030104 developmental biology Endocrinology medicine.anatomical_structure Glucose embryonic structures biology.protein Molecular Medicine GLUT1 Female hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery Vasoactive Intestinal Peptide |
Zdroj: | Biochimica et biophysica acta. Molecular basis of disease. 1867(10) |
ISSN: | 1879-260X |
Popis: | Glucose uptake by the placenta and its transfer to the fetus is a finely regulated process required for placental and fetal development. Deficient placentation is associated with pregnancy complications such as fetal growth restriction (FGR). The vasoactive intestinal peptide (VIP) has embryotrophic effects in mice and regulates human cytotrophoblast metabolism and function. Here we compared glucose uptake and transplacental transport in vivo by VIP-deficient placentas from normal or VIP-deficient maternal background. The role of endogenous VIP in placental glucose and amino acid uptake was also investigated. Wild type C57BL/6 (WT) or VIP+/- (VIP HT) females were mated with WT, VIP knock-out (VIP KO) or VIP HT males. Glucose uptake and transplacental transport were evaluated by the injection of the fluorescent d-glucose analogue 2-NBDG in pregnant mice at gestational day (gd) 17.5. Glucose and amino acid uptake in vitro by placental explants were measured with 2-NBDG or 14C-MeAIB respectively. In normal VIP maternal background, fetal weight was reduced in association with placental VIP deficiency, whereas placental weight was unaltered. Paradoxically, VIP+/- placentas presented higher glucose uptake and higher gene expression of GLUT1 and mTOR than VIP+/+ placentas. However, in a maternal VIP-deficient environment placental uptake and transplacental transport of glucose increased while fetal weights were unaffected, regardless of feto-placental genotype. Results point to VIP-deficient pregnancy in a normal background as a suitable FGR model with increased placental glucose uptake and transplacental transport. The apparently compensatory actions are unable to sustain normal fetal growth and could result in complications later in life. |
Databáze: | OpenAIRE |
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