Stadtmauer Daniel J
Department of Genetics, Harvard Medical School, Boston, MA, USA.
Department of Evolutionary Biology, University of Vienna, Vienna, Wien, Austria.
Evol Med Public Health. 2025 Sep 18;13(1):307-330. doi: 10.1093/emph/eoaf025. eCollection 2025.
Evolutionary biologists have long been fascinated by pregnancy sickness, the heritable, stereotyped syndrome in early pregnancy that usually consists of benign nausea and vomiting and in around 1% of cases progresses to the pathological extreme hyperemesis gravidarum. Identification of the placental hormone GDF15 as a principal causal factor justifies reassessment of its proximate and ultimate causes. This Review synthesizes knowledge of pregnancy sickness at the four levels of analysis of classical ethology-mechanism, development, phylogeny, and adaptive function. Emerging insight into GDF15's role in innate sickness behaviors suggests pregnancy sickness is a heightened state of pre-existing behavioral defenses triggered by placental production of an emetogenic hormone which may hold a different primary function. Comparison of transcriptomes reveals that placental production rose 100- to 1000-fold to human-like levels in catarrhine primates, and is low or absent in New World monkeys, rodents, and other mammals, with the possible exception of elephants. This suggests that pregnancy sickness is phylogenetically restricted yet not human-specific, and associates with innovations in syncytiotrophoblast biology rather than diet. I re-evaluate leading adaptive hypotheses (prophylactic, metabolic rewiring, placental growth, and anti-rejection) and argue that the key to adjudicating among them hinges on whether GDF15 acts locally through non-canonical receptors and whether additional factors distinguish pregnancy sickness from sickness behavior. Finally, I evaluate explanations for the persistent risk of hyperemesis gravidarum in modern humans, including trade-offs, mismatch, and conflict. With recent advances, pregnancy sickness is not just a curiosity of human evolution, but a compelling opportunity to investigate the mechanistic bases of complex adaptive behaviors.
长期以来，进化生物学家一直对妊娠反应着迷，这是一种在妊娠早期出现的可遗传的、刻板的综合征，通常表现为良性恶心和呕吐，约1%的病例会发展为病理性的妊娠剧吐。胎盘激素生长分化因子15（GDF15）被确定为主要致病因素，这使得有必要重新评估其近因和终极原因。本综述综合了经典动物行为学四个分析层面（机制、发育、系统发育和适应功能）关于妊娠反应的知识。对GDF15在先天性疾病行为中作用的新见解表明，妊娠反应是由胎盘产生的一种致吐激素触发的、预先存在的行为防御的增强状态，而这种激素可能具有不同的主要功能。转录组比较显示，在旧世界猴中，胎盘产生量增加了100至1000倍，达到类人水平，而在新大陆猴、啮齿动物和其他哺乳动物（大象可能除外）中则很低或不存在。这表明妊娠反应在系统发育上受到限制，但并非人类特有的，并且与合体滋养层生物学的创新而非饮食有关。我重新评估了主要的适应性假说（预防、代谢重组、胎盘生长和抗排斥），并认为在这些假说中进行裁决的关键在于GDF15是否通过非经典受体在局部起作用，以及是否有其他因素将妊娠反应与疾病行为区分开来。最后，我评估了现代人类中妊娠剧吐持续存在风险的解释，包括权衡、不匹配和冲突。随着最近的进展，妊娠反应不仅是人类进化中的一个奇特现象，而且是研究复杂适应性行为机制基础的一个引人注目的机会。
