Imprinted Genes, Placental Development and Fetal Growth

Abstract

In mammals, imprinted genes have an important role in feto-placental development. They affect the growth, morphology and nutrient transfer capacity of the placenta and, thereby, control the nutrient supply for fetal growth. In particular, the reciprocally imprinted Igf2–H19 gene complex has a central role in these processes and matches the placental nutrient supply to the fetal nutrient demands for growth. Comparison of Igf2P0 and complete Igf2 null mice has shown that interplay between placental and fetal Igf2 regulates both placental growth and nutrient transporter abundance. In turn, epigenetic modification of imprinted genes via changes in DNA methylation may provide a mechanism linking environmental cues to placental phenotype, with consequences for development both before and after birth. Changes in expression of imprinted genes, therefore, have major implications for developmental programming and may explain the poor prognosis of the infant born small for gestational age and the wide spectrum of adult-onset diseases that originate in utero.

Litter-size-dependent intrauterine growth restriction in sheep

“…These results clearly suggest that in multi-foetal pregnancies, reduced placentome number does not account for foetal IUGR. Possible explanations for litter-size-dependent IUGR might be the inability of the maternal system fully to meet nutrient demands of multiple conceptuses, mutual growth interference among sibling foetuses, and maternal inhibition of placental and foetal growth in the case of multiple conceptuses by downregulation genes controlling placental growth and nutrient transport, as was noted in the case of maternal genomic imprinting (Isles and Holland, 2005;Angiolini et al, 2006;Cattanach et al, 2006;Fowden et al, 2006b). …”

“…A substantial proportion of known imprinted genes are involved in the control of foetal growth and placental development (Reik and Walter, 2001). In general, paternally expressed genes enhance placental growth, while Gootwine, Spencer and Bazer maternally expressed genes reduce placental size and its nutrient-transport ability (Isles and Holland, 2005;Angiolini et al, 2006;Cattanach et al, 2006;Fowden et al, 2006b).…”

Expression profiles of genes regulating dairy cow fertility: recent findings, ongoing activities and future possibilities

“…Imprinted genes may account for only a fraction of the genome (e.g. , 0.3% (Miozzo and Simoni, 2002)), but these affect early development strongly and may have a major impact on fertility (Fowden et al, 2006). , Gebert et al (2006 compared bovine oocyte to sperm DNA and reported on a differentially methylated region in the imprinted insulin-like growth factor 2 gene and this allows further work on gene-specific methylation patterns during pre-implantation development.…”

Dysregulation of methylation and expression of imprinted genes in oocytes and reproductive tissues in mice of advanced maternal age

“…The intergenomic conflict hypothesis theorizes that maternal expression (paternal silencing/methylation) of imprinted genes distribute maternal nutrient resources equally among current and future offspring, while maintaining the health of the female. Paternally expressed genes (maternal silencing/methylation) promote fetal and placental growth by maximizing maternal resources to the current offspring at the expense of the maternal health and future generations [17][18][19]. Knockout studies of maternally expressed genes result in fetal and placental overgrowth, whereas knockout of paternally expressed genes result in fetal and placental growth restriction [17].…”

“…Paternally expressed genes (maternal silencing/methylation) promote fetal and placental growth by maximizing maternal resources to the current offspring at the expense of the maternal health and future generations [17][18][19]. Knockout studies of maternally expressed genes result in fetal and placental overgrowth, whereas knockout of paternally expressed genes result in fetal and placental growth restriction [17]. Dysregulation of methylation patterns may be an indicator for epigenetic instability which could result in infertility [20].…”