Genetic inheritance is a physical link that connects our birth parents; one half of two sets of chromosomes that interlock to form our own unique set of molecular instructions for life.
As cooperative as that sounds, the stakes are not the same for each parent, making these chromosomes the battleground for the future of the mother and offspring.
New research on pregnant mice reveals an example of genetic tricks that manipulate the mother’s response to glucose to provide more sugary nutrients to her growing fetus.
This trick is not so scary and really quite common. Called ‘genetic imprint‘ causes a copy of an inherited gene to be made smothered by removable molecules so that the other copy can be freely expressed.
In this new study, researchers found that mouse fetuses use a copy of an imprinted gene they inherited from their father to leech nutrients from their mother across the placenta.
“It’s the first direct evidence that a gene inherited from the father signals the mother to pass nutrients to the fetus,” says Reproductive biologist Amanda Sferruzzi-Perri from the University of Cambridge is a co-author of the study.
Of the genes a baby inherits, copies from the father tend to promote fetal growth, while copies from the mother limit it. Even if a mother feeds her baby during pregnancy, she must ensure her own survival.
“Although the pregnancy is mostly cooperative, there is a lot of room for potential conflict between the mother and the baby,” says Co-lead author Miguel Constancia, epigeneticist at the University of Cambridge.
Genetics, along with the hormones produced in the placenta, are thought to play a key role in the nutritional ‘tug of war’ of Constancia pregnancy adds.
Scientists assumed that evolution had provided fetuses with ingenious ways to meet their nutritional needs, just as mothers maintained their own nutritional needs. Researchers had even studied a hormone called insulin-like growth factor 1 (Igf2). Notice it “strong effects of fetal growth”.
However, the exact mechanisms remained unclear: The placenta, where Igf2 and many other hormones are produced and act, “is arguably the most important organ in the body, but paradoxically it is also the least understood,” according to a 2015 review article explained.
In a series of animal experiments, Cambridge University physiologist Jorge Lopez-Tello and a team of colleagues tinkered with the gene that codes for Igf2, which resembles the hormone insulin.
insulin helps cells take up glucose from the blood, and expectant mothers become insulin resistant in the later stages of pregnancy to ensure their cells aren’t absorbing the nutrients their babies need.
The mouse experiments showed that Igf2 produced in placenta cells actually increases a pregnant mother’s insulin resistance and thereby transfers more glucose to the fetus.
“This means that the mother’s tissues don’t take up glucose, so nutrients are more readily available in the circulation and can be transferred to the fetus.” explained Sferruzzi-Perri.
“Until now, we didn’t know that part of the Igf2 gene’s role is to regulate signaling to the mother to allocate nutrients to the fetus,” she says adds.
Mice without a working copy of their father’s Igf2 gene in placental cells were smaller at birth because their mother didn’t send them enough nutrients.
This mechanism, if correct, would explain exactly what we see in it some human growth disorders.
The offspring of the animal also showed the first signs of diabetes and obesity later in life, the researchers found.
Further studies on earlier and later stages of pregnancy are needed to understand the full extent to which Igf2 manipulates maternal metabolism in humans and how it interacts with other placental hormones.
The study was published in cellular metabolism.
