Fathers' Genomic Imprinting Promotes Mothers' Loving Care

By passing down an epigenetically paternalized gene to their offspring, fathers may indirectly influence mothers to maximize their nurturing behavior after the offspring are born. This effect, which was observed among mice and may be present in other mammals, including humans, concerns the Phlda2 gene, which controls the size of the placental endocrine compartment that produces hormones. Whether this gene is switched “off” (the paternalized state) or “on” (the maternalized state) influences whether the mother mouse spends more time nest building, or nursing and grooming her pups.

These findings appeared in the journal PLOS Biology, in an article titled, “Maternal care boosted by paternal imprinting in mammals.” The article, which was contributed by scientists based at Cardiff University’s School of Biosciences, speculates that imprinting of Phlda2 contributed to increased maternal care during the evolution of mammals.

In the current study, the Cardiff team extends its previous investigations of the hormonal signals given off from the placenta during pregnancy. For example, the team previously reported that a placental gene similar to Phlda2 is linked to prenatal depression.

“We are currently asking whether similar gene changes are associated with poor quality maternal care in the Grown in Wales Study” said Rosalind John, Ph.D., the lead author of the current study and professor and head of biomedicine, at Cardiff’s school of biosciences. “More work must be done to further our understanding in how this works in humans.”

The placenta transports nutrients to the growing fetus during pregnancy and gives off hormonal signals in the mother’s bloodstream to establish and maintain a successful pregnancy. As well as being involved in nurturing the baby throughout the pregnancy, the placental signals are thought to be important for programming a mother’s behavior, preparing them for their new role as a parent.

These hormones are produced by placental cells called spongiotrophoblasts, whose proliferation (and therefore whose hormone output) is held in check by Phlda2. But here’s the twist; like most genes, the developing fetus has two copies of the Phlda2 gene, but unlike most genes, only one copy of Phlda2 is active. This is due to an evolutionarily intriguing phenomenon called genomic imprinting, whereby only the gene copy from one parent is switched on. In the case of Phlda2, it’s the father’s copy that’s silent.

“We show,” the authors of the PLOS Biology article wrote, “that wild-type 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 behavior.

“Female mice pregnant with pups carrying the highest dose of Phlda2 favor nest building over caring for their young or themselves. In contrast, dams exposed to the lowest Phlda2 dose while pregnant prioritize nurturing and grooming of their young and personal grooming.”

Why are these findings important? Parenthood can be seen as a conflict between the interests of the two parents, with the father (and his genes) favoring maximum investment in the offspring, potentially at the expense of the mother’s best interests. The results of this study suggest that the father, by causing his Phlda2 gene to be silent in the fetus, can even affect the nurturing behavior of the mother after his offspring have been born.

The authors speculate that this may have relevance to humans, as levels of Phlda2 gene activity vary between human pregnancies and inversely correlate with placental hormones. Changes in the mother’s priorities during gestation and after birth are critically important for the wellbeing of the new baby and their lifelong mental health.