Genomic imprinting, action, and interaction of maternal and fetal genomes

Abstract

Mammalian viviparity (intrauterine development of the fetus) introduced a new dimension to brain development, with the fetal hypothalamus and fetal placenta developing at a time when the fetal placenta engages hypothalamic structures of the maternal generation. Such transgenerational interactions provide a basis for ensuring optimal maternalism in the next generation. This success has depended on genomic imprinting and a biased role of the matriline. Maternal methylation imprints determine parent of origin expression of genes fundamental to both placental and hypothalamic development. The matriline takes a further leading role for transgenerational reprogramming of these imprints. Developmental errors are minimized by the tight control that imprinted genes have on regulation of downstream evolutionary expanded gene families important for placental and hypothalamic development. Imprinted genes themselves have undergone purifying selection, providing a framework of stability for in utero development with most growth variance occurring postnatally. Mothers, not fathers, take the lead in the endocrinological and behavior adaptations that nurture, feed, and protect the infant. In utero coadaptive development of the placenta and hypothalamus has thus required a concomitant development to ensure male masculinization. Only placental male mammals evolved the sex determining SRY, which activates Sox9 for testes formation. SRY is a hybrid gene of Dgcr8 expressed in the developing placenta and Sox3 expressed in hypothalamic development. This hybridization of genes that take their origin from the placenta and hypothalamus has enabled critical in utero timing for the development of fetal Leydig cells, and hence testosterone production for hypothalamic masculinization.genomic imprinting | genomic reprogramming | hypothalamus | placenta | development

Expression of imprinted genes in placenta is associated with infant neurobehavioral development

“…23,24 In addition, a number of GWAS have identified genetic variation at or near imprinted genes associated with autism and other mental deficits. 13 Importantly, the placenta and brain are the 2 organs that have the most active imprinted genome because both organs are under tremendous selective pressure to optimize growth and development, and both are thought to have undergone co-adaptation, leading to co-expression of many of the same imprinted genes. 13,25 Although the expression of imprinted genes is highly regulated, our group and others have demonstrated subtle variation in the expression of these genes in the placenta of healthy newborns 15,26,27 ; yet, little is known about the relationships between this variation in expression and newborn and childhood outcomes.…”

“…13 Importantly, the placenta and brain are the 2 organs that have the most active imprinted genome because both organs are under tremendous selective pressure to optimize growth and development, and both are thought to have undergone co-adaptation, leading to co-expression of many of the same imprinted genes. 13,25 Although the expression of imprinted genes is highly regulated, our group and others have demonstrated subtle variation in the expression of these genes in the placenta of healthy newborns 15,26,27 ; yet, little is known about the relationships between this variation in expression and newborn and childhood outcomes. We demonstrated that infants with specific, coordinated profiles of expression of subset of imprinted genes in the placenta were at increased risk for sub-optimal performance on measures of movement quality and for exhibiting an elevated number of signs of physiologic stress of abstinence.…”

“…11,12 In addition, the pattern of expression of imprinted genes in the placenta demonstrates significant similarity to that observed in the developing brain. 13 Prior investigations examining placental expression of imprinted genes have demonstrated low transcriptional noise, highlighting the importance of the fine-tuned regulation of this gene subset for proper infant development. 14 The specific importance of placental expression of the imprinted gene IGF2 has also been demonstrated through placental specific disruption in mice, resulting in increased reactivity to stress stimuli; this phenotype was not observed in total knockouts.…”

New insights into molecular mechanisms of epigenetic regulation in kidney disease

“…The use of NGS has made it possible to identify the precise positions of epigenetic modification . More and more studies are reporting on the role of epigenetic mechanisms in embryogenesis, cell differentiation, genome imprinting, inactivation of X chromosomes and ageing …”

Epigenetic changes in the developing brain: Effects on behavior

“…Thus, at the Sackler Colloquium mechanisms discussed were those for maternal behaviors (13), sexual behaviors and stress (14), and hypothalamically controlled behaviors (15). Circadian-regulated behaviors (16) clearly represent a case of normal behaviors epigenetically regulated, whereas problematic and abnormal behaviors, such as in Prader-Willi syndrome (17), and changes in behavior during aging were also discussed.…”