Crisóstomo Luís, Bourgery Matthieu, Rato Luís, Raposo João F, Batterham Rachel L, Kotaja Noora, Alves Marco G
Departamento de Anatomia, e UMIB-Unidade Multidisciplinar de Investigação em Biomedicina, ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal.
Laboratory for Integrative and Translational Research in Population Health (ITR), University of Porto, 4050-600 Porto, Portugal.
Biomedicines. 2022 Apr 15;10(4):909. doi: 10.3390/biomedicines10040909.
Excessive adiposity caused by high-fat diets (HFDs) is associated with testicular metabolic and functional abnormalities up to grand-offspring, but the mechanisms of this epigenetic inheritance are unclear. Here we describe an association of sperm small non-coding RNA (sncRNA) with testicular "inherited metabolic memory" of ancestral HFD, using a transgenerational rodent model. Male founders were fed a standard chow for 200 days (CTRL), HFD for 200 days (HFD), or standard chow for 60 days followed by HFD for 140 days (HFDt). The male offspring and grand-offspring were fed standard chow for 200 days. The sncRNA sequencing from epidydimal spermatozoa revealed signatures associated with testicular metabolic plasticity in HFD-exposed mice and in the unexposed progeny. Sperm tRNA-derived RNA (tsRNA) and repeat-derived small RNA (repRNA) content were specially affected by HFDt and in the offspring of HFD and HFDt mice. The grand-offspring of HFD and HFDt mice showed lower sperm counts than CTRL descendants, whereas the sperm miRNA content was affected. Although the causality between sperm sncRNAs content and transgenerational epigenetic inheritance of HFD-related traits remains elusive, our results suggest that sperm sncRNA content is influenced by ancestral exposure to HFD, contributing to the sperm epigenome up to the grand-offspring.
高脂饮食（HFD）导致的过度肥胖与直至孙代的睾丸代谢和功能异常有关，但其表观遗传遗传机制尚不清楚。在这里，我们使用跨代啮齿动物模型描述了精子小非编码RNA（sncRNA）与祖先HFD的睾丸“遗传代谢记忆”之间的关联。雄性奠基者分别喂食标准饲料200天（CTRL）、HFD 200天（HFD）或标准饲料60天，然后HFD 140天（HFDt）。雄性后代和孙代喂食标准饲料200天。来自附睾精子的sncRNA测序揭示了与暴露于HFD的小鼠和未暴露后代的睾丸代谢可塑性相关的特征。精子tRNA衍生RNA（tsRNA）和重复序列衍生小RNA（repRNA）含量特别受HFDt以及HFD和HFDt小鼠后代的影响。HFD和HFDt小鼠的孙代精子数量低于CTRL后代，而精子miRNA含量受到影响。虽然精子sncRNAs含量与HFD相关性状的跨代表观遗传遗传之间的因果关系仍然难以捉摸，但我们的结果表明，精子sncRNA含量受祖先HFD暴露的影响，直至孙代都对精子表观基因组有贡献。
