Maternal placenta modulates a deleterious fetal mutation†

Abstract

Intrauterine growth restriction (IUGR) is caused by dysregulation of placental metabolism. Paternally inherited IUGR mutations in the fetus influence maternal physiology via the placenta. However, it is not known whether the maternal placenta also affects the extent of IUGR in such fetuses. In cattle and other ruminants, maternal-fetal communication occurs primarily at the placentomes. We previously identified a 3΄ deletion in the noncoding MER1 repeat containing imprinted transcript 1 (MIMT1) gene that, when inherited from the sire, causes IUGR and late abortion in Ayshire cattle with variable levels of severity. Here, we compared the transcriptome and genomic imprinting in fetal and maternal placentome components of wild-type and MIMT1Del/WT fetuses before IUGR became apparent, to identify key early events. Transcriptome analysis revealed fewer differentially expressed genes in maternal than fetal MIMT1Del/WT placentome. AST1, within the PEG3 domain, was the only gene consistently reduced in IUGR in both fetal and maternal samples. Several genes showed an imprinting pattern associated with IUGR, of which only secernin 3 (SCRN3) and paternally expressed 3 (PEG3) were differentially imprinted in both placentome components. Loss of strictly monoallelic, allele-specific expression (∼80:20) of PEG3 in the maternal MIMT1Del/WT placenta could be associated with incomplete penetrance of MIMT1Del. Our data show that dysregulation of the PEG3 domain is involved in IUGR, but also reveal that maternal placental tissues may affect the penetrance of the paternally inherited IUGR mutation.

Analysis of Gene Expression Profiles in the Liver of Rats With Intrauterine Growth Retardation

“…Combined with this method, pathway analysis can map gene expression data into appropriate pathway maps based on their molecular associations and functional annotations. By now, a limited number of studies have focused on gene expression patterns in IUGR ( 11 – 13 ). Therefore, we used Affymetrix Gene Chip to evaluate differential gene expression profiling by comparing IUGR newborn rats liver with control.…”

Investigation of allele-specific expression of genes involved in adipogenesis and lipid metabolism suggests complex regulatory mechanisms of PPARGC1A expression in porcine fat tissues

“…The frequency of ASE varies with species, tissue and individual physiological status, and analysis of its pattern may elucidate underlying regulatory mechanisms affecting many complex traits [ 8 , 9 ]. About 20% of human genes are estimated to preferentially express one allele [ 10 , 11 ], and recent high throughput RNA sequencing studies suggest it may be even more widespread [ 12 ]. For example, 52% of genes exhibit ASE in pig brain [ 13 ], and 89% of bovine genes showed allelic imbalance in at least one of 18 tissues tested in a single individual [ 14 ].…”