2023-12-13 ケンブリッジ大学
◆つわりは妊娠の7割に影響し、一部では重度化し入院が必要となることもある。現在の治療法が不十分な中、GDF15によるつわりのメカニズム解明は治療法の開発に繋がる可能性があります。
<関連情報>
- https://www.cam.ac.uk/stories/pregnancy-sickness-cause
- https://www.cam.ac.uk/stories/pregnancy-sickness-cause
GDF15が妊娠中の吐き気と嘔吐の母体リスクに関連 GDF15 linked to maternal risk of nausea and vomiting during pregnancy
M. Fejzo,N. Rocha,I. Cimino,S. M. Lockhart,C. J. Petry,R. G. Kay,K. Burling,P. Barker,A. L. George,N. Yasara,A. Premawardhena,S. Gong,E. Cook,D. Rimmington,K. Rainbow,D. J. Withers,V. Cortessis,P. M. Mullin,K. W. MacGibbon,E. Jin,A. Kam,A. Campbell,O. Polasek,G. Tzoneva,F. M. Gribble,G. S. H. Yeo,B. Y. H. Lam,V. Saudek,I. A. Hughes,K. K. Ong,J. R. B. Perry,A. Sutton Cole,M. Baumgarten,P. Welsh,N. Sattar,G. C. S. Smith,D. S. Charnock-Jones,A. P. Coll,C. L. Meek,S. Mettananda,C. Hayward,N. Mancuso & S. O’Rahilly
Nature Published:13 December 2023
DOI:https://doi.org/10.1038/s41586-023-06921-9
We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.
Abstract
GDF15, a hormone acting on the brainstem, has been implicated in the nausea and vomiting of pregnancy (NVP) including its most severe form, Hyperemesis Gravidarum (HG), but a full mechanistic understanding is lacking [1-4]. Here we report that fetal production of GDF15, and maternal sensitivity to it, both contribute substantially to the risk of HG. We confirmed that higher GDF15 levels in maternal blood are associated with vomiting in pregnancy and HG. Using mass spectrometry to detect a naturally-labelled GDF15 variant we demonstrate that the vast majority of GDF15 in the maternal plasma is derived from the feto-placental unit. By studying carriers of rare and common genetic variants we found that low levels of GDF15 in the non-pregnant state increase the risk of developing HG. Conversely, women with beta-thalassemia, a condition where GDF15 levels are chronically high [5], report very low levels of NVP. In mice, the acute food intake response to a bolus of GDF15 is influenced bi-directionally by prior levels of circulating GDF15 in a manner suggesting that this system is susceptible to desensitization. Our findings support a putative causal role for fetally-derived GDF15 in the nausea and vomiting of human pregnancy, with maternal sensitivity, at least partly determined by pre-pregnancy exposure to the hormone, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG.
