During the first trimester of pregnancy, it is common to experience nausea or vomiting, and although the exact causes are not known, they have been attributed to a mechanism that protects the fetus against the ingestion of potentially toxic substances present in food. Now, new research carried out by the University of Cambridge (United Kingdom) and the University of Southern California (USC) (USA) has revealed that a hormone produced by the fetus – the protein GDF15 – and the sensitivity of the pregnant woman to This hormone is the cause of nausea and vomiting during pregnancy.
Up to seven out of every 10 pregnant women experience nausea and vomiting, which in some cases becomes so severe (it is estimated that between one and three in every 100 pregnancies) that it can even put the life of the fetus and the mother at risk and require Intravenous fluid replacement to prevent dangerous levels of dehydration. The so-called hyperemesis gravidarum is the most common cause of hospitalization of women during the first three months of pregnancy.
The culprit that causes many women, including the Duchess of Cambridge, to get so sick that they even need to be admitted to the hospital is the GDF15 protein, but the intensity of the pregnant woman’s symptoms depends on a combination of the amount of the hormone produced by the fetus and the exposure the mother had to this hormone before becoming pregnant. The findings have been published in Nature and suggest a potential strategy to prevent hyperemesis gravidarum by exposing mothers to GDF15 before pregnancy so that they develop tolerance to it.
The key to preventing hyperemesis gravidarum
The researchers analyzed data from women recruited for several studies and used a combination of approaches including human genetics, new ways of measuring hormones in pregnant women’s blood, and studies in cells and mice. In this way, they demonstrated that the degree of nausea and vomiting that a woman experiences during pregnancy is directly related to both the amount of GDF15 produced by the fetal part of the placenta that reaches the bloodstream, and her sensitivity to the nauseating effect of this hormone.
GDF15 is produced at low levels in all tissues outside of pregnancy. A woman’s sensitivity to the hormone during pregnancy depends on the amount she was exposed to before conception: women with normally low levels of GDF15 in their blood are at greater risk of experiencing severe nausea and vomiting during pregnancy.
Researchers found that a rare genetic variant that puts women at much higher risk of hyperemesis gravidarum was associated with lower levels of the hormone in blood and tissues outside of pregnancy. Similarly, women with the inherited blood disorder beta-thalassemia, which causes their prepregnancy GDF15 levels to be naturally very high, have little or no nausea or vomiting.
“Hopefully, now that we understand the cause of hyperemesis gravidarum, we are one step closer to developing effective treatments.”
“Most women who become pregnant will experience nausea and discomfort at some point and, although this is not pleasant, for some women it can be much worse: they become so sick that they require treatment and even hospitalization. “Now we know why,” said Professor Sir Stephen O’Rahilly, co-director of the Institute for Metabolic Sciences and director of the Metabolic Diseases Unit at the University of Cambridge Medical Research Council, who led the work.
“Knowing this gives us a clue as to how we can prevent it from happening. “It also gives us more confidence 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 to treat this disorder.”
Mice exposed to high, acute levels of GDF15 showed signs of loss of appetite, suggesting they were experiencing nausea, but mice treated with a long-acting form of GDF15 did not show similar behavior when exposed to acute levels of the drug. hormone. Researchers believe that building a woman’s tolerance to the hormone before pregnancy could be the key to preventing disease.
Co-author Dr. Marlena Fejzo of the Department of Population and Public Health Sciences at the University of Southern California, whose team had previously identified the genetic association between GDF15 and hyperemesis gravidarum, has first-hand experience with this condition. “When I was pregnant, I got so sick that I could barely move without feeling sick. When I tried to find out why, I realized how little was known about my condition, even though morning sickness is very common.” “Hopefully, now that we understand the cause of hyperemesis gravidarum, we are one step closer to developing effective treatments to prevent other mothers from going through what many women and I have experienced,” she concludes.
