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A new study titled: Maternal care boosted by paternal imprinting in mammals, published in the open access journal, PLOS Biology, found that a father’s genes, as expressed by the placenta in a pregnant woman, can influence the level of care a mom provides for her growing baby during pregnancy as well as after the baby is born.

Although this is a study with mice, researchers believe that it does have relevance to human pregnancy because placental endocrine dysfunction could contribute to a mood disorder and the researchers have already published that a gene in the same family is abnormally expressed in the placenta of women with depression in pregnancy.

“I have been studying a really remarkable family of genes called ‘imprinted genes’ for the last 20 years,” Rosalind M. John told us. John is a professor of developmental epigenetics and the head of biomedicine at the Cardiff School of Biosciences at Cardiff University in the United Kingdom. In addition to being interested in imprinted genes, John became a lot more interested in pregnancy when she became a mother in 2001.

“Motherhood requires a really amazing change in priorities and one that surprised me as I’ve always been so career-focused,” John told us. “Research on pregnancy, and pregnant women in general, does not get the attention it deserves or the funding. We can send spaceships to Mars but we still can’t tell a mother how big her baby will be or predict which mothers will have problems with their pregnancy or develop a mood disorder. A healthy pregnancy sets the trajectory for health throughout life and deserves much more focus.”

John explained to us that imprinted genes have this name because they carry an imprint from the mother or the father which results in one copy being switched off in the children.

“This is really odd because we are all taught at school that two copies of a gene are important to protect us against mutations, and much safer than only one copy,” John told us. “So why turn off one copy?”

 John’s research group found out that one of these imprinted genes called ‘Phlda2’ plays an important role in the placenta regulating the production of placental hormones. Placental hormones are critically important in pregnancy as they induce adaptations in the mother required for healthy fetal growth. There was also some indirect evidence that placental hormones play a role in inducing maternal instinct. 

“Women are not born with a maternal instinct,” John told us. “This behaviour develops during pregnancy to prepare the mother-to-be for the new and demanding role of caring for her baby. Until now, direct experimental evidence to support the theory that placental hormones trigger this motherly love by acting directly on the brain of the mother has been lacking. This led to my idea that this gene expressed in the offspring’s placenta could influence maternal behaviour, which was entirely novel.” 

To test the theory that our imprinted gene could influence the mother’s behaviour, John and her colleagues generated pregnant mice by in vitro fertilization (IVF) carrying embryos with different copies of Phlda2.

“We used IVF to keep all the mothers genetically identical,” John told us. “This resulted in genetically identical pregnant female mice exposed to different amounts of placental hormones – either too low, normal or too high.”

The researchers found that female mice exposed in pregnancy to low amounts of placental hormones were much more focused on nest building (housekeeping) and spent less time looking after their pups or themselves than normal mice. In contrast, female mice exposed to high placental hormones neglected their nests and spent more time looking after their pups and more time self-grooming.

“We also found changes in the brain before the pups were born so we know that the change in priorities started before birth,” John told us. “I was surprised that it worked! It was such a speculative idea and we really struggled to get funding to do the work.” 

John explained to us that it is possible that problems with the placenta could mis-program maternal nurturing in a human pregnancy potentially manifesting as a mood disorder. One in seven mothers experience postpartum depression and one in four women experience significant anxiety while pregnant.

“After we found out that Phlda2 could influence maternal behaviour in mice, we asked whether there were changes in this gene in human placenta from pregnancies where women were either diagnosed with clinical depression or self reported depression in pregnancy,” John told us.

Phlda2 seems to be ok according to John, but the researchers found another gene that belongs to the same imprinted gene family called ‘PEG3’ that is expressed at lower than normal levels.

“Strangely, this seems to only be in placenta from boys,” John told us. She and her colleagues will be exploring this further with their own human cohort study called ‘Grown in Wales’ at Cardiff University. “We are now looking at placental hormones in the mother’s blood and gene expression in the placenta to test the idea that the genes we are studying in mice are misregulated in the placenta of pregnancies where the mothers suffer with depression and/or anxiety.”