Some low birth-weight babies could be a result of a battle of the sexes, UK research suggests. A team at the Babraham Institute in Cambridge has found that if you delete a part of a gene inherited from the father, the placenta and ultimately the baby is much smaller.
The finding nicely supports the theory of genetic conflict between parents. According to that theory, it鈥檚 in dad鈥檚 interest to make babies as big and healthy as possible, to give them, and dad鈥檚 genes, the best chances at survival. Mum, on the other hand, needs to preserve her resources so she can have more babies, thereby propagating her genes.
The theory suggests that one of the weapons in the battle is 鈥渋mprinting鈥�. Although children inherit versions of genes from both parents, when genes are imprinted, only one is ever activated. Paternally-expressed genes, the theory goes, will make the baby bigger, while maternally-expressed ones will restrain fetal growth.
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One gene known to be paternally imprinted is Igf2, which codes for insulin-like growth factor II, a growth-promotor. This gene is expressed in both the fetus and the placenta. But Miguel Constancia and colleagues found a way to selectively delete in mice only that portion of that gene that specifically affects the placenta. Just prior to birth, mutant fetuses were only 69 per cent of the normal weight.
Constancia thinks problems with imprinting of this gene might cause low birth-weight in some human babies. 鈥淚f the mechanism is conserved, we鈥檇 like to test growth-restricted babies and see if there are problems with IGF II,鈥� he says. But he cautions that there are many other imprinted genes that appear to affect fetal growth.
Fewer nutrients
After creating the mutant mice, the team monitored both passive and active flow of nutrients from mother to fetus, the size of the placenta and the size of the fetus.
On embryonic day 12 鈥� the mouse typically gestates for 20 days 鈥� the placenta was already unusually small. At day 20, the fetuses were getting only 60 per cent of the nutrients that normal fetuses received.
The selective deletion restricted the size of the placenta just as much as when the whole gene was gone, the researchers found. This suggests it is responsible for how the IGF II protein works in the placenta.
Benjamin Tycko at Columbia University in New York says that the Igf2 gene may not be the best test of the theory, since it sparked it in the first place. 鈥淏ut I am struck by the lack of any knockouts that actively contradict the model,鈥� he says.
Journal reference: Nature (vol 417, p 945)