Cross-species comparison of pregnancy-induced GDF15

Anders Bue Klein, Pablo Ranea-Robles, Trine Sand Nicolaisen, Cláudia Gil, Kornelia Johann, Julia Prats Quesada, Nina Pistoljevic, Kathrine V R Hviid, Line F Olsen, Simone Margaard Offersen, Jørn Wulff Helge, Henriette Svarre-Nielsen, Jaco Bakker, Maximilian Kleinert, Christoffer Clemmensen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

3 Citations (Scopus)
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Abstract

Growth differentiation factor 15 (GDF15) is a stress-induced cytokine. Although the exact physiological function of GDF15 is not yet fully comprehended, the significant elevation of circulating GDF15 levels during gestation suggests a potential role for this hormone in pregnancy. This is corroborated by genetic association studies in which GDF15 and the GDF15 receptor, GDNF Family Receptor Alpha Like (GFRAL) have been linked to morning sickness and hyperemesis gravidarum (HG) in humans. Here, we studied GDF15 biology during pregnancy in mice, rats, macaques, and humans. In contrast to macaques and humans, mice and rats exhibited an underwhelming induction in plasma GDF15 levels in response to pregnancy (~75-fold increase in macaques vs. ~2-fold increase in rodents). The changes in circulating GDF15 levels were corroborated by the magnitude of Gdf15 mRNA and GDF15 protein expression in placentae from mice, rats, and macaques. These species-specific findings may help guide future studies focusing on GDF15 in pregnancy and on the evaluation of pharmacological strategies to interfere with GDF15-GFRAL signaling to treat severe nausea and HG.

Original languageEnglish
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume325
Issue number4
Pages (from-to)E303-E309
ISSN0193-1849
DOIs
Publication statusPublished - 2023

Keywords

  • Faculty of Science
  • GDF15
  • GFRAL
  • Emesis
  • Nausea
  • Pregnancy
  • Placenta
  • Primates
  • Macaques

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