ArticleReproductive sciences (Thousand Oaks, Calif.)2011
Differential gene expression in the adrenals of normal and anencephalic fetuses and studies focused on the Fras-1-related extracellular matrix protein (FREM2) gene.
Article in Reproductive sciences (Thousand Oaks, Calif.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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7 authors at 4 institutions in 1 country.
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Abstract
precisMany genes are differentially expressed in normal compared to anencephalic human fetal adrenals (HFAs), especially the Fras-1-related extracellular matrix protein (FREM2) gene. FREM2 expression appears to be regulated by adrenocorticotrophic hormone (ACTH). CONTEXT: The expression profiles of genes responsible for cortical growth and zonation in the HFA gland are poorly characterized. The neural tube disorder anencephaly is associated with fetal adrenal hypoplasia with a large size reduction of the fetal zone of the HFA.
objectiveTo determine gene expression profile differences in the adrenals of anencephalic compared to normal HFAs to identify genes that may play important roles in adrenal development. DESIGN AND
methodsFresh tissues were obtained at the time of autopsy from normal and anencephalic human fetuses delivered at mid-gestation. The following techniques were used: cell culture, messenger RNA (mRNA) extraction, microarray analysis, complementary DNA (cDNA) synthesis, quantitative real-time reverse transcriptase polymerase chain reaction (QT-PCR).
resultsWe identified over 40 genes expressed at levels 4-fold or greater in the normal versus anencephalic HFAs and that 28 genes were expressed at increased levels in the anencephalic HFA. The expression of FREM2 at approximately 40-fold greater levels in the normal HFA compared to the HFA of anencephalic fetuses was confirmed by QT-PCR. Expression of FREM2 in the kidney was not significantly different between normal and anencephalic fetuses. In cultured HFA cells, ACTH treatment for 48 hours increased the expression of FREM2 and a gene responsive to ACTH, CYP17, but not tyrosine hydroxylase.
conclusionsAbnormal expression of many genes may be involved in the adrenal hypoplasia seen in anencephaly. FREM2 appears to be regulated by ACTH and is the most differentially expressed gene, which may be important in the development and function of the HFA, particularly the fetal zone of the HFA.
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