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Gestational folate deficiency alters embryonic gene expression and cell function.

ABSTRACT: Folic acid is a nutrient essential for embryonic development. Folate deficiency can cause embryonic lethality or neural tube defects and orofacial anomalies. Folate receptor 1 (Folr1) is a folate binding protein that facilitates the cellular uptake of dietary folate. To better understand the biological processes affected by folate deficiency, gene expression profiles of gestational day 9.5 (gd9.5) Folr1^-/- embryos were compared to those of gd9.5 Folr1^+/+ embryos. The expression of 837 genes/ESTs was found to be differentially altered in Folr1^-/- embryos, relative to those observed in wild-type embryos. The 837 differentially expressed genes were subjected to Ingenuity Pathway Analysis. Among the major biological functions affected in Folr1^-/- mice were those related to 'digestive system development/function', 'cardiovascular system development/function', 'tissue development', 'cellular development', and 'cell growth and differentiation', while the major canonical pathways affected were those associated with blood coagulation, embryonic stem cell transcription and cardiomyocyte differentiation (via BMP receptors). Cellular proliferation, apoptosis and migration were all significantly affected in the Folr1^-/- embryos. Cranial neural crest cells (NCCs) and neural tube explants, grown under folate-deficient conditions, exhibited marked reduction in directed migration that can be attributed, in part, to an altered cytoskeleton caused by perturbations in F-actin formation and/or assembly. The present study revealed that several developmentally relevant biological processes were compromised in Folr1^-/- embryos.

SUBMITTER: Seelan RS

PROVIDER: S-EPMC7855679 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Arsenic is a contaminant found worldwide in drinking water and food. Epidemiological studies have correlated arsenic exposure with reduced weight gain and improper muscular development, while in vitro studies show that arsenic exposure impairs myogenic differentiation. The purpose of this study was to use Fundulus heteroclitus or killifish as a model organism to determine if embryonic-only arsenic exposure permanently reduces the number or function of muscle satellite cells. Killifish embryos were exposed to 0, 50, 200, or 800 ppb arsenite (AsIII) until hatching, and then juvenile fish were raised in clean water. At 28, 40, and 52 weeks after hatching, skeletal muscle injuries were induced by injecting cardiotoxin into the trunk of the fish just posterior to the dorsal fin. Muscle sections were collected at 0, 3 and 10 days post-injury. Collagen levels were used to assess muscle tissue damage and recovery, while levels of proliferating cell nuclear antigen (PCNA) and myogenin were quantified to compare proliferating cells and newly formed myoblasts. At 28 weeks of age, baseline collagen levels were 105% and 112% greater in 200 and 800 ppb groups, respectively, and at 52 weeks of age, were 58% higher than controls in the 200 ppb fish. After cardiotoxin injury, collagen levels tend to increase to a greater extent and take longer to resolve in the arsenic exposed fish. The number of baseline PCNA(+) cells were 48-216% greater in 800 ppb exposed fish compared to controls, depending on the week examined. However, following cardiotoxin injury, PCNA is reduced at 28 weeks in 200 and 800 ppb fish at day 3 during the recovery period. By 52 weeks, there are significant reductions in PCNA in all exposure groups at day 3 of the recovery period. Based on these results, embryonic arsenic exposure increases baseline collagen levels and PCNA(+) cells in skeletal muscle. However, when these fish are challenged with a muscle injury, the proliferation and differentiation of satellite cells into myogenic precursors is impaired and instead, the fish appear to be favoring a fibrotic resolution to the injury.

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Gestational folate deficiency alters embryonic gene expression and cell function.

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