New Map Reveals Pregnancy’s Impact on Organ Interactions

Scientists have mapped for the first time the metabolic changes that different parts of a primate's body undergo during pregnancy. The results suggest that pregnancy-related conditions such as preeclampsia and gestational diabetes may be due to “rewiring” errors when these changes occur.

Outside of pregnancy, different body systems normally “supply” each other with molecular nutrients, known as metabolites, in relatively equal exchange.

However, during pregnancy, major changes occur in tissues throughout the body. for example, Heart pumps up to 40% more. However, the thymus gland, which is involved in the immune system, “shrinks very quickly” to prevent rejection of the fetus. See Chan Ng at the Chinese Academy of Sciences in Beijing.

After studying Effects of metabolites on stem cells, Ng was curious about the role they play during pregnancy. During this period, “a lot of things are growing and regenerating…It's something you only see in comic books and superhero movies where people transform,” he says.

To learn more, Ng et al. collected 273 tissue samples from 12 cynomolgus monkeys (cynomolgus monkey), including when the monkey was in each trimester of pregnancy and when it was not pregnant. Samples were taken from 23 body parts, including five areas of her body: uterus, liver, spinal cord, skin, blood and heart.

The researchers analyzed the samples for metabolites and compared each site during non-pregnancy to the equivalent site during the third trimester.

As expected, when the macaques were not pregnant, Ng said, the metabolites were distributed fairly evenly across the body. But to her surprise, pregnancy caused her interactions to be “dramatically reprogrammed.”

For example, during the first trimester, the uterus reduced communication with the heart and skeletal muscles and instead “coupled” with the developing placenta. During the second trimester of pregnancy, the fully formed placenta began pumping “large amounts of metabolites” to the heart, ovaries, and liver. On the other hand, the uterus gradually migrated towards union with the scalp by the third trimester of pregnancy.

Also, during the third trimester, important exchanges between skeletal muscles and the spinal cord took place. Researchers have not investigated why these coupling changes occur.

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

In a separate experiment, researchers took serum samples from 32 pregnant women and found that levels of the metabolite corticosterone were “significantly reduced” in patients with preeclampsia, Ng said. He states: Then, when they removed corticosterone from human placental cells in the lab, they caused pre-eclampsia-like inflammation. “Corticosterone is an important steroid in human pregnancy,” says Ng. “It’s been undervalued.”

The second important metabolite is thought to be palmitoylcarnitine, which helps process fatty acids and regulate immunity. Ongoing human stem cell research led by Ng suggests that human stem cells may be involved in gestational diabetes, he says.

Based on their findings, the researchers developed an “atlas” of 91 metabolites that consistently change in the tissues of pregnant cynomolgus monkeys. This provides a framework for the involvement of metabolites in regulating health during human pregnancy, Ng said. “There is a treasure trove of small molecules and metabolites that we have discovered. [which] I hope this will further encourage research into new treatments,” he says.

Previous studies have investigated metabolic changes such as: While pregnant rats and mice do, cynomolgus monkeys have reproductive systems much more similar to humans, Ng said. Even though macaques have a shorter gestation period than humans (about 26 weeks compared to the average 40 weeks), they still serve as a reliable model for human reproduction, especially pregnancy-related conditions, he said.