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Biological Chemistry

Researchers link fetal hormone to pregnancy nausea

Prior exposure level governs severity, suggesting a druggable mechanism

by Laurel Oldach
December 13, 2023

A crystal structure of a dimeric peptide hormone.
Credit: Xiong et al./RCSB Protein Data Bank
Growth/differentiation factor 15 (pictured) is released in response to cell stress in adult tissues.

Most people who become pregnant spend at least a little time feeling nauseous—but the cause, like many basic biological facts about pregnancy, has been elusive. In a small subset of pregnancies, vomiting is severe and incessant enough to send expecting parents to the hospital.

In a study published today, a team led by researchers at the University of Southern California and the University of Cambridge report that a peptide hormone called growth/differentiation factor 15, or GDF-15, likely causes pregnancy-related nausea (Nature 2023, DOI: 10.1038/s41586-023-06921-9) . They hope that prophylactic exposure to GDF-15 before pregnancy may mitigate the worst symptoms.

In an earlier genetic study, the researchers found a correlation between extreme vomiting during pregnancy and increases in GDF-15, which is known to signal part of the brain involved in nausea (Nat. Commun. 2018, DOI: 10.1038/s41467-018-03258-0) . But the hormone’s role was difficult to ascertain because it is produced in both adult and fetal tissues and because a common genetic variant interferes with an antibody-based assay that researchers once used to determine its levels.

After resolving the immunoassay problem, researchers used the genetic variant to their advantage. Using mass spectrometry in plasma from people with a different GDF-15 genotype than their fetuses’, they traced the bulk of circulating GDF-15 to the fetus and placenta. They also found that people with a genetic disorder that raises GDF-15 levels outside pregnancy are much less likely to feel queasy when pregnant—an effect they attributed to desensitization. Then, in mice, they observed that chronic low exposure reduces the effect of a large dose of GDF-15, suggesting that GDF-15 exposure before conception could help prevent severe vomiting in people.



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