Maternal vitamin A deficiency during pregnancy affects vascularized islet development.

Abstract

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.

• Authors: Chiao-Yun Chien, Hsuan-Shu Lee, Candy Hsin-Hua Cho, Kuo-I Lin, David Tosh, Ruei-Ren Wu, Wan-Yu Mao, Chia-Ning Shen
• Journal: The Journal of nutritional biochemistry (J Nutr Biochem) Vol. 36 Pg. 51-59 (10 2016) ISSN: 1873-4847 [Electronic] United States
• PMID: 27573099 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Benzaldehydes
• Benzoates
• Enzyme Inhibitors
• Receptors, Retinoic Acid
• Retinoids
• 4-(diethylamino)benzaldehyde
• Tretinoin
• 4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid
• Retinal Dehydrogenase

Topics

• Animals
• Animals, Newborn
• Benzaldehydes (pharmacology)
• Benzoates (pharmacology)
• Cell Differentiation (drug effects)
• Embryo, Mammalian (cytology, pathology)
• Enzyme Inhibitors (pharmacology)
• Female
• Fetal Development (drug effects)
• Insulin-Secreting Cells (drug effects, metabolism, pathology)
• Islets of Langerhans (blood supply, drug effects, metabolism, pathology)
• Maternal Nutritional Physiological Phenomena
• Mice, Inbred C57BL
• Mice, Transgenic
• Neovascularization, Physiologic (drug effects)
• Pregnancy
• Random Allocation
• Receptors, Retinoic Acid (agonists, antagonists & inhibitors, metabolism)
• Retinal Dehydrogenase (antagonists & inhibitors, metabolism)
• Retinoids (pharmacology)
• Tissue Culture Techniques
• Tretinoin (metabolism)
• Vitamin A Deficiency (metabolism, pathology)