Maternal vitamin A deficiency during pregnancy affects vascularized islet development

Autor: Candy Hsin-Hua Cho, Wan Yu Mao, Ruei Ren Wu, Kuo-I Lin, Hsuan-Shu Lee, David Tosh, Chiao Yun Chien, Chia-Ning Shen
Rok vydání: 2016
Předmět:
0301 basic medicine
Receptors
Retinoic Acid
Endocrinology
Diabetes and Metabolism
Clinical Biochemistry
Retinoic acid
Benzoates
Biochemistry
Fetal Development
Tissue Culture Techniques
Random Allocation
chemistry.chemical_compound
0302 clinical medicine
Pregnancy
Insulin-Secreting Cells
Retinoid
Enzyme Inhibitors
Nutrition and Dietetics
geography.geographical_feature_category
Vitamin A Deficiency
Cell Differentiation
Islet
Vascular endothelial growth factor
Benzaldehydes
Female
Vitamin
medicine.medical_specialty
medicine.drug_class
Neovascularization
Physiologic
Mice
Transgenic
Tretinoin
030209 endocrinology & metabolism
Biology
Islets of Langerhans
Retinoids
03 medical and health sciences
Internal medicine
medicine
Animals
Molecular Biology
geography
Fetus
Retinal Dehydrogenase
Maternal Nutritional Physiological Phenomena
Embryo
Mammalian
medicine.disease
Mice
Inbred C57BL
Vitamin A deficiency
Retinoic acid receptor
030104 developmental biology
Endocrinology
Animals
Newborn
chemistry
Zdroj: The Journal of Nutritional Biochemistry. 36:51-59
ISSN: 0955-2863
DOI: 10.1016/j.jnutbio.2016.07.010
Popis: Vitamin A deficiency is known to affect 20 million pregnant women worldwide. However, the prenatal effects of maternal vitamin A deficiency on pancreas development have not been clearly determined. The present study examined how maternal vitamin A deficiency affects fetal islet development. Vitamin A-deficient mice were generated by feeding female mice with a chemically defined diet lacking vitamin A prior to mating as well as during pregnancy. We found that maternal vitamin A deficiency during pregnancy affected fetal pancreas development. Although the exocrine differentiation appeared normal, development of islet tissue was impaired. In the pancreas of neonatal mice, only a few endocrine cell clusters were formed, and these cell clusters lacked capillary endothelial cells. To further determine how vitamin A metabolites, such as retinoic acid, regulate vascularized islet development, ex vivo culture of embryonic pancreas either in the presence of 4-diethylaminobenzaldehyde (DEAB; an inhibitor of retinaldehyde dehydrogenase), all-trans retinoic acid (atRA) or retinoic acid receptor agonist (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylenyl)-1-propenyl] benzoic acid (TTNPB) was carried out. We found that the addition of DEAB blocked vascularization and suppressed β-cell differentiation. Conversely, atRA or TTNPB promoted β-cell differentiation accompanied by enhanced expression of vascular basement component, laminin. We further demonstrated that atRA regulated vascularization via upregulating vascular endothelial growth factor-A (VEGF-A) secretion in embryonic pancreas and treatment with VEGF-A was able to partially rescue vascularization and β-cell differentiation in DEAB-treated embryonic pancreas cultures. The findings explain why maternal vitamin A deficiency affects fetal islet development and support an essential role of retinoid signaling in regulating vascularized islet development.
Databáze: OpenAIRE
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