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RNA Sequencing Exposes Adaptive and Immune Responses to Intrauterine Growth Restriction in Fetal Sheep Islets.
- Source :
-
Endocrinology [Endocrinology] 2017 Apr 01; Vol. 158 (4), pp. 743-755. - Publication Year :
- 2017
-
Abstract
- The risk of type 2 diabetes is increased in children and adults who exhibited fetal growth restriction. Placental insufficiency and intrauterine growth restriction (IUGR) are common obstetrical complications associated with fetal hypoglycemia and hypoxia that reduce the β-cell mass and insulin secretion. In the present study, we have defined the underlying mechanisms of reduced growth and proliferation, impaired metabolism, and defective insulin secretion previously established as complications in islets from IUGR fetuses. In an IUGR sheep model that recapitulates human IUGR, high-throughput RNA sequencing showed the transcriptome of islets isolated from IUGR and control sheep fetuses and identified the transcripts that underlie β-cell dysfunction. Functional analysis expanded mechanisms involved in reduced proliferation and dysregulated metabolism that include specific cell cycle regulators and growth factors and mitochondrial, antioxidant, and exocytotic genes. These data also identified immune responses, wnt signaling, adaptive stress responses, and the proteasome as mechanisms of β-cell dysfunction. The reduction of immune-related gene expression did not reflect a change in macrophage density within IUGR islets. The present study reports the islet transcriptome in fetal sheep and established processes that limit insulin secretion and β-cell growth in fetuses with IUGR, which could explain the susceptibility to premature islet failure in adulthood. Islet dysfunction formed by intrauterine growth restriction increases the risk for diabetes.<br /> (Copyright © 2017 Endocrine Society.)
- Subjects :
- Animals
Female
Fetal Growth Retardation genetics
Fetal Growth Retardation metabolism
Fetus
Islets of Langerhans metabolism
Placental Insufficiency genetics
Placental Insufficiency metabolism
Pregnancy
Sequence Analysis, RNA
Sheep
Signal Transduction physiology
Transcriptome
Adaptive Immunity physiology
Fetal Growth Retardation immunology
Islets of Langerhans immunology
Placental Insufficiency immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7170
- Volume :
- 158
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 28200173
- Full Text :
- https://doi.org/10.1210/en.2016-1901