We now have a map of how pregnancy changes the way organs interact

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Written By Margonoe Tumindax

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Mapping how interactions between different organs change during pregnancy could help us better understand conditions such as pre-eclampsia

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For the first time, scientists have mapped the metabolic changes that different parts of the body go through during a primate’s pregnancy. The results suggest that pregnancy-related conditions such as pre-eclampsia and gestational diabetes might be due to “rewiring” errors when these changes occur.

Outside of pregnancy, different bodily systems usually “feed” each other molecular nutrients, known as metabolites, in a relatively even exchange.

But tissues throughout the body undergo significant changes during pregnancy. For instance, the heart increases its pumping volume by up to 40 per cent. But the thymus, involved in the immune system, “shrinks away really fast” to prevent rejection of the fetus, says Shyh-Chang Ng at the Chinese Academy of Sciences in Beijing.

Having studied the effects of metabolites on stem cells, Ng was curious about the role they play in pregnancy. During this time, “a lot of things are growing and regenerating… That’s something you only see in cartoons or superhero movies where the person transforms”, he says.

To learn more, Ng and his colleagues took 273 tissue samples from 12 crab-eating macaques (Macaca fascicularis), including when the monkeys were in each of the three trimesters of pregnancy, as well as when they weren’t pregnant. The samples came from 23 bodily sites, including the uterus, liver, spinal cord, skin, blood and five regions of the heart.

The researchers analysed the samples for metabolites, comparing each site during the non-pregnant state with its equivalent during the three trimesters.

As expected, when the macaques weren’t pregnant, their metabolites were shared fairly evenly across parts of the body, says Ng. But to his surprise, pregnancy resulted in the exchange getting “reprogrammed dramatically”.

In the first trimester, for example, the uterus decreased its exchanges with the heart and skeletal muscles, “coupling” instead with the developing placenta. During the second trimester, the fully formed placenta started sending out “a whole host of metabolites” to the heart, ovaries and liver, while the uterus gradually shifted towards coupling with the scalp by the third trimester.

Also in late pregnancy, the skeletal muscles had significant exchanges with the spinal cord. The researchers didn’t investigate why any of these coupling changes occur.

When the “reprogrammed” flow of metabolites deviates from what is considered normal during pregnancy, certain conditions could arise, says Ng.

In another experiment, the researchers took blood serum samples from 32 pregnant women, finding a “huge drop” in levels of the metabolite corticosterone among those with pre-eclampsia, says Ng. They then deprived human placenta cells of corticosterone in the laboratory, which resulted in pre-eclampsia-like inflammation. “Corticosterone is a key steroid in human pregnancy,” says Ng. “It’s been underappreciated.”

A second key metabolite appears to be palmitoylcarnitine, which helps process fatty acids and regulate immunity. An ongoing human stem cell study led by Ng suggests it might play a role in gestational diabetes, he says.

Off the back of their findings, the researchers have developed an “atlas” of 91 metabolites that consistently change in the tissues of pregnant crab-eating macaques. This provides a framework for the involvement of metabolites in regulating health during human pregnancy, says Ng. “There’s a treasure trove of small molecules and metabolites that we found, [which] I hope will help spur further research into new therapeutics,” he says.

Previous studies have investigated metabolic changes in pregnant rats and mice, but crab-eating macaques have a far more human-like reproductive system, says Ng. Despite having shorter pregnancies than people – averaging about 26 weeks versus 40 weeks – the macaques still serve as reliable models for human reproduction, particularly for pregnancy-related conditions, he says.

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