Pregnancy causes a tremendous adaptation in the female body as it nurtures and tolerates a growing fetus and supports the placenta. However, the changes in chemicals and hormones that affect maternal organs are still poorly understood. Now, a team of researchers in China is taking a step towards filling this gap by analyzing the metabolic activity of a wide range of organs in pregnant monkeys.
Some organs, including the liver and heart, became hotspots of activity as expected, and the team reported surprising metabolic changes in other tissues, including **. In addition to a better understanding of the molecular processes at play, the authors claim that these findings could reveal metabolic disorders during pregnancy, such as preeclampsia and gestational diabetes, and lead to diagnosis and intervention.
I was surprised to find that metabolic changes during pregnancy go beyond the metabolic organs that are usually relevant," said Yuyu Niu, a developmental biologist at Kunming University of Science and Technology who was not involved in the study. The study, published today in the journal CELL, "should be considered a significant contribution to reproductive biology and women's health research," she added.
Studying the metabolome, or collection of metabolites, such as amino acids, lipids, sugars, and organic acids, which mediate and regulate biochemical processes in the human body, has been challenging. There have been studies on blood and urine during pregnancy in humans, but these studies have not linked metabolites to specific organs. (Sampling requires organ collection, which is not ethically and practically feasible for humans.) Studies of pregnant rodents are not satisfactory because they differ markedly from primate pregnancies. It is important to note that rodents do not naturally experience metabolic diseases such as gestational diabetes, preeclampsia, or hypertension, while some people develop these diseases when they become pregnant.
So the team turned to cynomolgus monkeys, where nearly 300 samples of 23 different tissues were collected from animals that had never been pregnant and animals in early, middle and late stages of pregnancy and their metabolites were evaluated.
The metabolome determines the biological structure and function of an organ," explains Hongmei Wang, a reproductive biologist at the Institute of Zoology of the Chinese Academy of Sciences and one of the authors of the new study. She and her colleagues hypothesized that the dynamics of metabolites drive changes in various organs caused by pregnancy.
Using a technique called liquid chromatography-mass spectrometry to identify and quantify metabolites in samples, the team identified 91 metabolites that have a potential role in helping the body adapt to pregnancy. Notably, levels of certain metabolites rise dramatically, while levels of others drop dramatically, not only in the known major metabolic organs – the liver, pancreas, and heart – but also in tissues that are generally considered not severely affected by pregnancy, including certain muscles and **. In the tissues examined, the concentrations of most metabolites also change as pregnancy progresses.
Brittany Needham, a biochemist at Indiana University School of Medicine, who was not involved in the study, said it was surprising to see the changes in the muscles and the molecules in the **. "However, ask those who have been pregnant if they have only noticed the change in *** officer, and the list of other organizations affected will be longer than the 23 studied here! ”
One of the limitations, said Mads Melbye, an epidemiologist at the Danish Cancer Institute, was that the team only studied the monkeys at three time points during their 165-day gestation. Melbye co-led a study published in the journal Cell in 2020 that looked at metabolites in weekly blood samples from 30 pregnant women and found that metabolic expression patterns "varied greatly in each few days of pregnancy," he said. But he noted that it is not easy to take weekly samples of metabolite levels in organs.
The results of this study may have implications for conditions such as preeclampsia. Preeclampsia can lead to high blood pressure during pregnancy and can be fatal to both the fetus and the mother if left untimed**. In the new study, researchers found high levels of the metabolite corticosterone in the placenta of pregnant monkeys. Then, in laboratory experiments using human stem cells, the team showed that corticosterone is essential for regulating placental function. In addition, they also found that pregnant women with preeclampsia had lower levels of corticosterone in their blood than those without it. Ng Shyh-Chang, a stem cell biologist at IOZ and co-author of the study, said that in many cases, preeclampsia is not detected until the placenta has been destroyed. He and his co-authors wrote: "(Identifying) maternal corticosterone deficiency may be useful in the clinical diagnosis of preeclampsia. ”
Melbye says the link between corticosterone deficiency and preeclampsia is interesting. "What remains to be proven is how clear it is for preeclampsia and how clear it is for early pregnancy," he said. Although the new findings pave the way for a better understanding of pregnancy mechanisms, the significance of many metabolic changes remains to be determined. ”
The authors agree that their** is just a starting point. Their study "sheds a lot of light on potential functional, pregnancy-adaptive metabolites," Ng Shyh-Chang said. "We certainly hope others will find out more details. ”