Maternal care boosted by paternal imprinting in mammals

Abstract

In mammals, mothers are the primary caregiver, programmed, in part, by hormones produced during pregnancy. High-quality maternal care is essential for the survival and lifelong health of offspring. We previously showed that the paternally silenced imprinted gene pleckstrin homology-like domain family A member 2 ( Phlda2) functions to negatively regulate a single lineage in the mouse placenta called the spongiotrophoblast, a major source of hormones in pregnancy. Consequently, the offspring’s Phlda2 gene dosage may influence the quality of care provided by the mother. Here, we show that wild-type (WT) female mice exposed to offspring with three different doses of the maternally expressed Phlda2 gene—two active alleles, one active allele (the extant state), and loss of function—show changes in the maternal hypothalamus and hippocampus during pregnancy, regions important for maternal-care behaviour. After birth, WT dams exposed in utero to offspring with the highest Phlda2 dose exhibit decreased nursing and grooming of pups and increased focus on nest building. Conversely, ‘paternalised’ dams, exposed to the lowest Phlda2 dose, showed increased nurturing of their pups, increased self-directed behaviour, and a decreased focus on nest building, behaviour that was robustly maintained in the absence of genetically modified pups. This work raises the intriguing possibility that imprinting of Phlda2 contributed to increased maternal care during the evolution of mammals.

Author summary

Female mammals are primed during pregnancy for their new role as a mother caring for their newborn. Indirect evidence suggests that this behaviour is, in part, instructed by hormones produced by the foetally derived placenta. We previously reported that the Phlda2 gene controls the size of the placental endocrine compartment that produces hormones. Phlda2 is subject to the remarkable epigenetic process called genomic imprinting, in which one parental allele is switched off. In the case of Phlda2, this is the paternal allele. This raises the intriguing possibility that the father’s genome influences the quality of care that offspring receive from their mothers. Here, we show via genetic manipulation of pup embryos that female mice pregnant with pups carrying the highest dose of Phlda2 favour nest building over caring for their young or themselves. In contrast, dams exposed to the lowest Phlda2 dose while pregnant prioritise nurturing and grooming of their young and personal grooming. These changes in maternal focus suggest the possibility that imprinting of Phlda2 contributed to enhanced maternal care in mammals. This study also presents a unique example of how the genetic makeup of offspring can influence maternal behaviour.