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.
Highlights
High-quality maternal care is vitally important for newborn survival and their behavioural and metabolic health later in life, evidenced by the catastrophic consequences when maternal care is poor or absent [1,2,3] (S1 Table)
We previously reported that the pleckstrin homology-like domain family A member 2 (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
Summary
High-quality maternal care is vitally important for newborn survival and their behavioural and metabolic health later in life, evidenced by the catastrophic consequences when maternal care is poor or absent [1,2,3] (S1 Table). Maternal care provision comes at the cost of the mother’s later reproductive fitness, whereas the paternal interest is best served by prolonged care of progeny exclusively by the dam. Imprinted genes, expressed from a single parental allele as a consequence of germline epigenetic events [4], are thought to be a physical embodiment of this conflict between male and female mammals over maternal investment in offspring [5, 6]. ‘paternalisation’ (silencing of paternal allele) is proposed to secure higher maternal investment, while ‘maternalisation’ counteracts to protect maternal reproductive fitness [5]. Examples of increased maternal care providing more compelling evidence for a purposeful phenomenon are exceptionally rare and almost invariably involve hormonal manipulations
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