Imprinted genes and the epigenetic regulation of placental phenotype.
Imprinted genes are expressed in a parent-of-origin manner by epigenetic modifications that silence either the paternal or maternal allele. They are widely expressed in fetal and placental tissues and are essential for normal placental development. In general, paternally expressed genes enhance feto-placental growth while maternally expressed genes limit conceptus growth, consistent with the hypothesis that imprinting evolved in response to the conflict between parental genomes in the allocation of maternal resources to fetal growth. Using targeted deletion, uniparental duplication, loss of imprinting and transgenic approaches, imprinted genes have been shown to determine the transport capacity of the definitive mouse placenta by regulating its growth, morphology and transporter abundance. Imprinted genes in the placenta are also responsive to environmental challenges and adapt placental phenotype to the prevailing nutritional conditions, in part, by varying their epigenetic status. In addition, interplay between placental and fetal imprinted genes is important in regulating resource partitioning via the placenta both developmentally and in response to environmental factors. By balancing the opposing parental drives on resource allocation with the environmental signals of nutrient availability, imprinted genes, like the Igf2-H19 locus, may act as nutrient sensors and optimise the fetal acquisition of nutrients for growth. These genes, therefore, have a major role in the epigenetic regulation of placental phenotype with long term consequences for the developmental programming of adult health and disease.
Department of Physiology, Development and Neuroscience, Downing Street, Cambridge CB23EG, United Kingdom. alf1000@cam.ac.uk
A L
AL
Fowden
P M
PM
Coan
E
E
Angiolini
G J
GJ
Burton
M
M
Constancia
D000328:Adult; D000818:Animals; D044127:Epigenesis, Genetic; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D008431:Maternal-Fetal Exchange; D051379:Mice; D010641:Phenotype; D010929:Placentation; D011247:Pregnancy