miRNA在生育、肥胖与应激反应中的跨代与代际效应
The intergenerational and transgenerational effects of miRNAs in fertility, obesity and stress responses
摘要
本文为综述,系统总结miRNA失调在生殖、代谢与应激相关表型中的跨代和代际效应。作者主要通过PubMed以miRNA、transgenerational effect及生殖、激素、精子发生、肥胖、高脂饮食、糖尿病、应激、治疗等主题词检索文献。综述指出,环境污染物和内分泌干扰物可改变miRNA表达,损害性腺发育、减少原始生殖细胞、诱导颗粒细胞凋亡并干扰性激素合成;miRNA依赖通路还影响精子发生、精子功能及卵母细胞发育。父源高脂饮食和妊娠期糖尿病可改变miRNA谱,提高子代肥胖与代谢病风险;慢性应激改变生殖细胞和胚胎miRNA表达,可能影响后代应激反应与行为。总体认为miRNA失调可通过表观遗传机制跨代传递。
原文摘要
MicroRNAs (miRNAs) are key post-transcriptional regulators that play pivotal roles in diverse physiological and pathological processes. They primarily act by inhibiting protein translation and promoting degradation of messenger RNA (mRNA), thereby inducing post-transcriptional regulatory effects. Most miRNAs can travel through blood, in extracellular vesicles, and between maternal and fetal tissues. When altered miRNAs were present in germ cells, this induces epigenetic inheritance, which influences embryonic development after fertilization. Aberrant miRNA expression is associated with a wide range of human diseases. This review article will summarize current evidence on how miRNA dysregulation contributes to transgenerational effects on reproduction, metabolism, and stress-related phenotypes. This research focuses on the impacts of miRNAs on reproductive impairment, obesity, and stress-related phenotypes, and highlights evidence that these epigenetic changes can persist across multiple generations. Relevant studies were identified mainly through PubMed database using "miRNA" and "transgenerational effect", with a third keyword according to the topic of interest, including "reproduction", "hormones", "spermatogenesis", "obesity", "high-fat diet", "diabetes", "stress", and "therapy". In reproduction, environmental pollutants (including endocrine disruptors) can alter miRNA expression, impairing gonadal development, reducing primordial germ cells, inducing granulosa cell apoptosis, and disrupting sex hormone synthesis. miRNA-dependent pathways also affect spermatogenesis, sperm function, and oocyte development. In obesity, miRNAs regulate adipogenesis by modulating signaling pathways and transcription programs that control fat-cell formation. Paternal high-fat diet and gestational diabetes can shift miRNA profiles, raising offspring risk for obesity and metabolic disease. Chronic stress changes miRNA expression in germ cells and embryos, shaping stress reactivity and social behavior in later generations. Prenatal maternal stress is linked to lasting psychiatric vulnerability in offspring, with effects potentially persisting across multiple generations without continued stress. Overall, miRNA dysregulation can impair reproduction, metabolism, and stress responses, and these effects may be transmitted transgenerationally via epigenetic mechanisms.
推荐理由:该综述将miRNA介导的生殖、代谢与应激跨代效应整合起来,对理解配子表观遗传和ART相关环境暴露风险有参考价值;但属于叙述性综述,无原始数据,转化落地有限。
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