Babies use a 'greedy gene' to control mum

A new study has shown that babies use a ‘greedy’ gene in the placenta that connects the developing baby to its mother to ‘remote-control’ the mum’s metabolism into feeding them extra food before they are born. We - and the mice used in the study - inherit copies of this gene from both our parents, but only the version that comes from dad is turned on. Amanda Sferruzzi-Perri studies fetal and placental physiology at the University of Cambridge…

Amanda - The placenta is connected to the foetus, and within the foetal blood there are messages communicating foetal demands for nutrients. So the amazing thing about the placenta is it's responding to both the mother and the foetus at the same time to try and control how the foetus is growing to best grow it healthy and large enough, but without compromising the mother.

Chris - So the placenta is sensing what the baby needs, the developing baby, and it's sensing what the mum's got to give away. And if there's a disparity, then it's going to provoke the mother to liberate more resources so that it meets the demands of the developing baby?

Amanda - That's right. And that's exactly what we tried to test. We selectively altered the signalling cells in the placenta that are responsible for communicating that need of the foetus to the mother.

Chris - Do you know what the nature of the signal is? What is the message that the developing baby is putting into the mum to make her liberate more energy and so on?

Amanda - Yeah. We identified several hormones that we think are really important in mediating this communication with the mum. They regulate the way in which the mother's tissues produce and respond to insulin, which is a key hormone that controls glucose and fat levels in the mother's circulation during normal pregnancy. A critical thing that the mother has to undergo is to reduce her ability to respond to insulin. And so the hormones that are coming out of the placenta are causing lowered insulin sensitivity so that the mother's liver, her skeletal muscle, her fat tissue doesn't suck up those nutrients. Instead they're made available in the circulation so they can be transferred to the foetus for growth.

Chris - So what happened when you shut off the ability of the placenta to make that signal?

Amanda - The mum held onto more nutrients, particularly glucose and lipids, and she used them instead for her body. And what that meant was that the foetus received fewer nutrients. They were born smaller. And surprisingly, when we looked at the health of the baby as it grew older, we found that they also had problems themselves in terms of their metabolism in later life.

Chris - Biologists often talk about a conflict between what the dad wants and what the mum wants because dad wants the biggest, healthiest, bounciest baby that he can breed in that mum to have the greatest chance of survival. And the mum wants the easiest baby she can give birth to with less cost to her health. So is that part and parcel of what you're seeing here, that argument?

Amanda - Yeah, it actually is. And you raised a really important point: the one way in which we studied this was to manipulate or alter the expression of the particular gene that is turned on when it is inherited from the dad. And actually, if you delete that gene from the placental signalling cells, the mum didn't free up the sugars, the lipids and the foetus was born growth restricted. And so we were able to really study this conflict between the parents operating at the level of the placenta, which was important in governing foetal growth.

Chris - So that's fascinating. You can inherit that gene from your mum and you can inherit it from your dad, but when you inherit it from your dad, it seems to have this effect of liberating resources from the mum. And if you turn it off, it stops that happening, but not the version you get from your mum?

Amanda - No, and that's because the mother's copy is normally turned off. And these types of genes are really unique. It's a small proportion of all the genes that we express in our body, but in this case, the gene is called IGF2. It's only turned on if we inherited it from our dad.

Chris - Wow. And given the relevance of insulin and diabetes in pregnancy, because some women succumb to gestational diabetes they develop a diabetic state when they are pregnant, it does have implications for their health later in life, is that tied up to this as well then?

Amanda - It is. And interestingly, women who develop gestational diabetes may have overproduction of hormones from the placenta. And there's also some data that suggests that if the copy of IGF2, this important gene in the placenta that is turned on from the father, if that's produced even more in pregnancy, there is a greater chance that the mother will develop diabetes in pregnancy.