Regulation of supply and demand for maternal nutrients in mammals by imprinted genes

Abstract

The placenta has evolved in eutherian mammals primarily to provide nutrients for the developing fetus. The genetic control of the regulation of supply and demand for maternal nutrients is not understood. In this review we argue that imprinted genes have central roles in controlling both the fetal demand for, and the placental supply of, maternal nutrients. Recent studies on Igf2 (insulin-like growth factor 2) knockout mouse models provide experimental support for this hypothesis. These show effects on placental transport capacity consistent with a role of IGF-II in modulating both the placental supply and fetal demand for nutrients. Imprinting of genes with such functions may have coevolved with the placenta and new evidence suggests that transporter proteins, as well as the regulators themselves, may also be imprinted. These data and hypotheses are important, as deregulation of supply and demand affects fetal growth and has long term consequences for health in mammals both in the neonatal period and, as a result of fetal programming, in adulthood.

Mechanisms and evolution of genomic imprinting in plants

“…In agreement with the predictions of this theory, imprinting occurs in placental mammals and flowering plants, both contributing maternal resources to the progeny (Feil and Berger, 2007). Furthermore, many imprinted genes in mammals affect both the demand and supply of nutrients across the placenta, adding additional support to this theory (Reik et al, 2003). In flowering plants, imprinting occurs in embryo and endosperm; with the latter constituting a separate organism that similar to the placenta is dedicated to nourish the developing embryo.…”

Genomic imprinting and the social brain

“…There is ample evidence from a number of mouse studies regarding imprinted genes and resource allocation in utero that appears to support the predictions made by the kinship theory (Reik et al 2003). However, as discussed previously, there is also predicted to be selective pressure for the involvement of imprinted genes in the pre-weaning period, when the offspring are still dependent on their mother for resources (Constancia et al 2004;Isles & Holland 2005).…”

“…With regards to the former (mother-offspring interactions), the predictive actions of maternally and paternally imprinted genes are relatively straightforward, being an extension of previously established effects in utero (Reik et al 2003). However, whereas in utero where the differential interest regards the distribution of nutrient resources across the placenta, in the early postnatal period the definition of resources can be extended to include aspects of maternal care and mother-infant bonding.…”

A supply–demand model of fetal energy sufficiency predicts lipid profiles in male but not female Filipino adolescents

“…Given evidence that the fetal growth trajectory may be reset in response to maternal nutrition or hormonal cues during early pregnancy or the periconceptual period (Godfrey & Robinson, 1998), growth restriction of epigenetic origin might paradoxically protect the developing fetus against nutritional insufficiency by lowering the level of nutritional demand during later gestation. Current work on parent of origin effects (imprinting) on IGF-II and a related cluster of genes suggests a possible epigenetic basis for separate regulation of fetal demand and maternal supply, manifesting as differential expression of fetal growth-promoting and placental-supply limiting genes in the fetus and placenta (Reik et al, 2003). Our results, along with evidence for sex differences in the transgenerational effect of maternal constraint on birth weight (Price & Coe, 2000), suggest that these processes may vary in important ways in males and females.…”