How Dad’s Genes Can Prepare Mom for Parenthood

All life shares a common goal: survive and reproduce. But when it comes to parenthood, priorities don’t always translate between sexes. After depositing their genetic contributions, most mammalian dads will exit stage left to impregnate other females. Moms, on the other hand, tend to bear the brunt of the work when it comes to bearing and birthing young.

So how devoted will a mom be? It turns out that even after dad splits, he has a say.

Today, scientists report that a father may have the ability to dictate a mother’s attentiveness to their offspring—before it’s even born. The paternal genes a fetus carries can impact the maternal brain during pregnancy, priming her to allocate more or less of her time to tending to her kids.

A child that procures as many nutrients as possible from mom can secure a father’s lineage at no cost to him—but a mother still needs to prioritize her own wellbeing during pregnancy and early childcare.

This sexual conflict is well exemplified by a gene called Igf2, which drives the rapid growth of fetal cells. Like most of our genetic material, Igf2 is inherited in pairs—one copy from mom and one copy from dad. But in contrast to other genes, only the version from dad gets put to work. The Igf2 from mom, on the other hand, is stifled through a chemical modification that acts like a muffler on an engine. Mom’s Igf2 DNA undergoes no changes—but the gene’s instructions can no longer be heard over the din of the cellular milieu. The silence seems purposeful: If an error occurs that also switches on the mother’s copy of Igf2, the baby quickly balloons in size. This could be good news for dad—a big baby is more likely to survive—but mom can get in serious trouble if she has to carry and birth an unmanageably large fetus.

To guard against this possibility, females have developed their own failsafe: another gene called Igf2r. The “r” stands for “receptor”: the product of this gene can sop up free-floating IGF-2 proteins before they exert their growth-promoting effects. Unsurprisingly, dad’s copy of Igf2r stays quiet—his retort to the reticence of mom’s Igf2—but if paternal Igf2r accidentally mouths off, babies are born weighing too little. Between these two extremes is the typical outcome: a Goldilocks offspring that’s not too big and not too small, expressing dad’s Igf2 and mom’s Igf2r.

Such is the phenomenon of genomic imprinting—a form of non-genetic inheritance in which both copies of a gene exist, but only one parent’s version is left intact. Over 150 imprinted genes have been confirmed in mice, about half of which have conserved counterparts in humans. In effect, imprinting represents the earliest of parenting compromises.

Much of the research so far on imprinted genes has studied the immediate effects on the children that inherit them—for instance, how often a mouse pup cries for its mother. But senior author Rosalind John, a professor of biology at Cardiff University, suspected a father’s genetic heirlooms might also directly skew maternal behavior.

Previous work by John’s research group had found that expression of an imprinted gene called Phlda2 in a fetus hinders the growth of hormone-secreting placental cells. These hormones recruit nutrients to support early development. Unsurprisingly, the offspring’s paternal copy of Phlda2 is kept under wraps. But mothers want their copy to remain switched on: If left unchecked by Phlda2, these sugar-sapping hormones in the placenta could create a hoarder of a fetus, leaving little energy for mom.

Other researchers had noted that these hormones weren’t just working in the placenta, however. Throughout pregnancy, they were actually spreading throughout the mother’s body and accumulating in her brain—leading John to suspect that they could also be encouraging a mother to care for her young.

Pregnancy is a life-altering event—that much is obvious. Even before an infant is born, females undergo vast physiological and psychological changes—including a veritable swarm of hormones—that prime them for the daunting task of motherhood. “A new mother is primed during pregnancy,” explains John. “It’s really important for the wellbeing of the pups.”

And Phlda2’s status as an imprinted gene fell neatly in line with this: Manipulating mom’s parenting approach could be yet another way that a father sneakily exerts his influence over the future wellbeing of his child.

To explore this possibility, a team of researchers that included lead author Hugo Creeth, a biologist working under John’s supervision at Cardiff University, tested the effects of tinkering with fetal Phlda2 expression in mice. Typically, developing mice express only the mother’s copy of Phlda2 to keep these placental hormones from running rampant; silencing dad’s copy effectively halves the output of the gene’s instructions. The researchers genetically manipulated mouse embryos to flip on both copies of Phlda2, an extreme version of the maternal optimum, or neither copy of Phlda2, a condition that favored the fatherly ideal. They then implanted these high-dose and low-dose embryos, along with normal offspring expressing just the mom’s copy of Phlda2, into genetically unmanipulated mothers. As expected, the amount of Phlda2 in the womb altered the expression of neural genes late in pregnancy, confirming that the altered genetics were driving the production (or lack thereof) of placental hormones.

When the mouse pups were born, the researchers scrutinized the new mothers’ behavior during the first few days after birth, when childcare was most critical. New mouse mothers raise their offspring without any input from fathers, and must divide their time between self-care, nurturing several new pups, and maintaining their homes. There’s only so much time in the day—so a mom’s priorities strongly inform how she allocates her time to these tasks. The team was pleased to find that mouse moms who had carried pups with minimal Phlda2 (and a boost in maternal hormones) spent more time nursing their offspring and grooming themselves, and less time building nests. On the other hand, moms exposed to extra Phlda2 (and fewer maternal hormones) devoted themselves to nest building—a show of mouse “housekeeping,” according to Creeth—in lieu of fussing excessively over their young.

The researchers were somewhat surprised to see moms acting on the effects of muted Phlda2 spending more time on not only their young, but also themselves. Was this counterintuitive with the father’s priorities? But Creeth reasoned that the mice were ensuring their own wellbeing so they could adequately tend to their children. The logic is perhaps comparable to putting on your own oxygen mask before helping your child with hers—skip the first step, and you’re likely to both suffer the consequences.

“We had to rethink what defines good mothering,” Creeth explains. “There’s not a gold standard. It’s a sliding scale of priorities.”

However, because Phlda2 also affects the nourishment of the fetus, pups carrying extra Phlda2 also weighed less at birth. To ensure that the brain changes during pregnancy, and not how the pups looked or acted, were driving the changes in behavior, the researchers repeated their experiment, letting the mothers gestate with different doses of fetal Phlda2. But this time, immediately after the pups were born, they were swapped for newborns with normally imprinted Phlda2—and the results were the same.

This sealed the deal for John and her team. “Lots of studies had hinted at this before, but there had been no experiments,” she says. “It was a shot in the dark when we decided to do this experiment.” But the results were clear: the differences in fetal gene expression during pregnancy had been enough to rewire mom’s brain in a lasting way.

David Haig, a professor of evolutionary biology at Harvard University who studies genomic imprinting, praised the “elegant” study and its “very cool results.” “We’ve known for a long time that pregnancy affects maternal behavior after birth, but to show that there’s an effect from genes in the fetus is new,” says Haig, who was not affiliated with the work.

The team’s work lends credence to the idea that fathers don’t dictate the health of children through genetic inheritance alone. In cases like these, they can even utilize the fetus as a chemical envoy in this battle between male and female, swaying a mother’s priorities towards more attentive childcare.

Marisa Bartolomei, a professor of developmental biology at the University of Pennsylvania who studies genomic imprinting, highlighted the study’s “clever and creative” design. “This is the first time we’ve seen that the genes of the fetus affect parental care, irrespective of the mother’s genes,” says Bartolomei, who was not involved in the research. “This isn’t an idea that [many scientists] have talked about.”

In future work, John and her team hope to gain a better understanding of which exact hormones drive the effects they’ve observed. Additionally, although the pups in this study didn’t seem to suffer any ill effects from shifts in maternal care, there could be long-term changes not captured in this short time span. John is especially concerned about psychological outcomes, as low birth weight and postpartum depression have been linked to neurodevelopmental disorders in human children. Finally, because problems with Phlda2 have been found in some children with low birth weight, John hopes to use these findings and others to inform human reproductive health in the future.

Even before birth, children communicate their fathers’ intent in a way that sticks. The priorities of male and female don’t always match up—and in a way, imprinting is evolution timidly waving a white flag between the clashing sexes. But at the end of the day, a treatise, however tenuous, is reached: All’s fair in the war of love. “It’s all about balance,” says Creeth. “What [they both] ultimately want… is the best for the offspring.”

Katherine J. Wu | | READ MORE

Katherine J. Wu is a Boston-based science journalist and Story Collider senior producer whose work has appeared in National Geographic, Undark magazine, Popular Science and more. She holds a Ph.D. in Microbiology and Immunobiology from Harvard University, and was Smithsonian magazine's 2018 AAAS Mass Media Fellow.