GDF15 linked to maternal risk of nausea and vomiting during pregnancy.
GDF15 linked to maternal risk of nausea and vomiting during pregnancy.
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DOI：
10.1038/s41586-023-06921-9
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发表时间：
2024-01
影响因子：
6.7
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中科院分区：
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GDF15是一种作用于脑干的激素，已被认为与妊娠的恶心和呕吐有关，包括其最严重的形式妊娠剧吐(HG)，但缺乏完整的机制了解。在这里，我们报告胎儿产生GDF15和母体对GDF15的敏感性都是导致HG风险的重要因素。我们证实，孕妇血液中较高的GDF15水平与妊娠呕吐和HG有关。使用质谱仪检测一个自然标记的GDF15变体，我们证明了母体血浆中绝大多数GDF15来自胎儿-胎盘单位。通过对罕见和常见遗传变异携带者的研究，我们发现非妊娠状态下低水平的GDF15会增加发生HG的风险。相反，患有β-地中海贫血症的妇女报告的恶心和呕吐水平非常低。在小鼠中，对GDF15团注的急性食物摄入反应受到循环中GDF15先前水平的双向影响，这表明该系统容易脱敏。我们的发现支持胎儿来源的GDF15在人类怀孕的恶心和呕吐中的推定因果作用，母亲的敏感性，至少部分由孕前接触该激素决定，是其严重性的主要影响因素。他们还提出了以机制为基础的治疗和预防HG的方法。孕妇循环中GDF15水平的升高与严重的恶心和呕吐有关，怀孕期间对这些症状的敏感性部分取决于孕前这种激素的水平。
GDF15, a hormone acting on the brainstem, has been implicated in the nausea and vomiting of pregnancy, including its most severe form, hyperemesis gravidarum (HG), but a full mechanistic understanding is lacking. 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 β-thalassaemia, a condition in which GDF15 levels are chronically high, report very low levels of nausea and vomiting of pregnancy. 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 prepregnancy exposure to the hormone, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG. Elevated circulating levels of GDF15 in pregnant women are associated with severe nausea and vomiting, and sensitivity to such symptoms during pregnancy is partly determined by prepregnancy levels of this hormone.