小柯机器人

英国剑桥大学S. O’Rahilly研究团队发现，GDF15与孕妇怀孕期间恶心和呕吐的风险有关。相关论文于2023年12月13日在线发表在《自然》杂志上。

研究人员报告了胎儿产生的GDF15和母体对其的敏感性都会大大增加妊娠剧吐（HG）的风险。研究人员证实，母体血液中较高的GDF15水平与妊娠呕吐和HG相关。利用质谱法检测天然标记的GDF15变体，研究人员证明母体血浆中的GDF15绝大多数来自胎盘。通过研究罕见和常见基因变异的携带者，研究人员发现在非怀孕状态下，低水平的GDF15会增加罹患HG的风险。与此相反，β-地中海贫血症（GDF15水平长期处于高水平）妇女的妊娠恶心和呕吐（NVP）水平却很低。

在小鼠中，对栓塞GDF15的急性食物摄入反应受先前循环GDF15水平的双向影响，这表明该系统容易脱敏。这些研究结果支持胎儿衍生的GDF15在人类NVP中可能扮演的因果角色，而母体的敏感性（至少部分由孕前接触该激素决定）是影响恶心和呕吐严重程度的主要因素。这还提出了基于机制的治疗和预防HG的方法。

据了解，GDF15是一种作用于脑干的激素，与NVP（包括最严重的HG）有关，但目前还缺乏对其机理的全面了解。

附：英文原文

Title: GDF15 linked to maternal risk of nausea and vomiting during pregnancy

Author: Fejzo, M., Rocha, N., Cimino, I., Lockhart, S. M., Petry, C. J., Kay, R. G., Burling, K., Barker, P., George, A. L., Yasara, N., Premawardhena, A., Gong, S., Cook, E., Rimmington, D., Rainbow, K., Withers, D. J., Cortessis, V., Mullin, P. M., MacGibbon, K. W., Jin, E., Kam, A., Campbell, A., Polasek, O., Tzoneva, G., Gribble, F. M., Yeo, G. S. H., Lam, B. Y. H., Saudek, V., Hughes, I. A., Ong, K. K., Perry, J. R. B., Sutton Cole, A., Baumgarten, M., Welsh, P., Sattar, N., Smith, G. C. S., Charnock-Jones, D. S., Coll, A. P., Meek, C. L., Mettananda, S., Hayward, C., Mancuso, N., ORahilly, S.

Issue&Volume: 2023-12-13

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.

DOI: 10.1038/s41586-023-06921-9

Source: https://www.nature.com/articles/s41586-023-06921-9

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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