Morning sickness in pregnant women is caused by a protein (GDF15) – Research

The fetus’s hormone, GDF15, is the cause. It is a protein causes morning sickness in pregnant women.

Research headed by Cambridge has revealed the reasons behind the nausea and vomiting that many pregnant women have, as well as the reasons why some women become so ill that they require hospital admission.

The fetus’s hormone, GDF15, is the cause. It is a protein. However, the amount of the hormone generated by the fetus and the mother’s prior exposure to the hormone before becoming pregnant both influence how ill the mother feels.

The finding, which was published in Nature, suggests that exposing moms to GDF15 before becoming pregnant may help them become more resilient and reduce pregnancy illness.

Nausea and vomiting can afflict up to seven out of 10 pregnant women. It can be severe in some women, and it impacts one to three out of every 100 pregnancies; in these cases, the mother’s and the fetus’ lives may be in jeopardy, necessitating intravenous fluid replacement to prevent dangerously high levels of dehydration. The most frequent reason for hospital admissions among pregnant women in the first trimester is a condition known as hyperemesis gravidarum.

Pregnancy sickness may be treated with some therapies that are at least somewhat successful, but many women who suffer from it receive insufficient care due to a combination of factors including a general lack of knowledge about the problem and a fear of taking medicine while pregnant.

Pregnancy sickness was completely unknown till recently. Recent data from genetic and biochemical research has hinted that it may be related to the placenta’s synthesis of the hormone GDF15, which operates on the mother’s brain to induce nausea and vomiting.

Researchers from the University of Cambridge, Scotland, the USA, and Sri Lanka collaborated on an international study that has significantly advanced our understanding of the function of GDF15 in pregnancy illness, particularly hyperemesis gravidarum.

The group examined data from women who were chosen for various studies, such as those conducted at Peterborough City Hospital, which is part of the North West Anglia NHS Foundation Trust, and the Rosie Maternity Hospital, which is part of Cambridge University Hospitals NHS Foundation Trust. They employed a variety of methods, such as investigations in cells and mice, novel techniques for detecting hormones in the blood of expectant mothers, and human genetics.

The group examined data from women who were chosen for various studies, such as those conducted at Peterborough City Hospital, which is part of the North West Anglia NHS Foundation Trust, and the Rosie Maternity Hospital, which is part of Cambridge University Hospitals NHS Foundation Trust. They employed a variety of methods, such as investigations in cells and mice, novel techniques for detecting hormones in the blood of expectant mothers, and human genetics.

All tissues produce minimal amounts of GDF15 outside of pregnancy. The amount of the hormone the mother was exposed to before becoming pregnant affects how sensitive she is to it during pregnancy; women whose blood levels of GDF15 are typically low are more likely to have severe nausea and vomiting during pregnancy.

The scientists discovered that lower levels of the hormone in the blood and tissues outside of pregnancy were linked to a unique genetic mutation that significantly increases the risk of hyperemesis gravidarum in women. Similarly, little to no nausea or vomiting occurs in women who have the genetic blood condition beta-thalassemia, which results in naturally very high levels of GDF15 before pregnancy.

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Most women who become pregnant will experience nausea and sickness at some point, and while this is not pleasant, for some women it can be much worse – they’ll become so sick they require treatment and even hospitalisation. We now know why.

The baby growing in the womb is producing a hormone at levels the mother is not used to. The more sensitive she is to this hormone, the sicker she will become.

Knowing this gives us a clue as to how we might prevent this from happening. It also makes us more confident that preventing GDF15 from accessing its highly specific receptor in the mother’s brain will ultimately form the basis for an effective and safe way of treating this disorder.

Professor Stephen O’Rahilly, University of Cambridge

Mice given with a long-acting version of GDF15 did not exhibit comparable behaviour when exposed to acute amounts of the hormone, whereas mice subjected to acute, high levels of the hormone had symptoms of appetite loss, suggesting that they were experiencing nausea. The secret to avoiding illness, according to the experts, may lay in increasing a woman’s tolerance to the hormone before becoming pregnant.

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When I was pregnant, I became so ill that I could barely move without being sick. When I tried to find out why, I realised how little was known about my condition, despite pregnancy nausea being very common.

Hopefully, now that we understand the cause of hyperemesis gravidarum, we’re a step closer to developing effective treatments to stop other mothers going through what I and many other women have experienced.

Dr Marlena Fejzo, University of Southern California

The research involved collaboration between scientists at the University of Cambridge, University of Southern California, University of Edinburgh, University of Glasgow and Kelaniya University, Colombo, Sri Lanka.


Source: University of Cambridge Stories | With Creative Commons Attribution 4.0 International License

Journal Reference: Fejzo, M., Rocha, N., Cimino, I., Lockhart, S. M., Petry, C. J., Kay, R. G., Burling, K., Barker, P., George, A. L., Yasara, N., Premawardhena, A., Gong, S., Cook, E., Rimmington, D., Rainbow, K., Withers, D. J., Cortessis, V., Mullin, P. M., MacGibbon, K. W., . . . Mancuso, N. (2023). GDF15 linked to maternal risk of nausea and vomiting during pregnancy. Nature, 1-3. https://doi.org/10.1038/s41586-023-06921-9


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