Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Departments of Genetics and Pediatrics - Penn Epigenetics Institute, Institute of Regenerative Medicine, and Center for Women's Health and Reproductive Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Departments of Genetics and Pediatrics - Penn Epigenetics Institute, Institute of Regenerative Medicine, and Center for Women's Health and Reproductive Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Cell Rep. 2024 Sep 24;43(9):114698. doi: 10.1016/j.celrep.2024.114698. Epub 2024 Sep 2.
Sperm small RNAs have emerged as important non-genetic contributors to embryogenesis and offspring health. A subset of sperm small RNAs is thought to be acquired during epididymal transit. However, the identity of the specific small RNAs transferred remains unclear. Here, we employ Cre/Lox genetics to generate germline- and epididymal-specific Dgcr8 knockout (KO) mice to investigate the dynamics of sperm microRNAs (miRNAs) and their functions post-fertilization. Testicular sperm from germline Dgcr8 KO mice has reduced levels of 116 miRNAs. Enthrallingly, following epididymal transit, the abundance of 72% of these miRNAs is restored. Conversely, sperm from epididymal Dgcr8 KO mice displayed reduced levels of 27 miRNAs. This loss of epididymal miRNAs in sperm was accompanied by transcriptomic changes in embryos fertilized by this sperm, which was rescued by microinjection of epididymal miRNAs. These findings ultimately demonstrate the acquisition of miRNAs from the soma by sperm during epididymal transit and their subsequent regulation of embryonic gene expression.
精子小 RNA 已成为胚胎发生和后代健康的重要非遗传贡献因素。一部分精子小 RNA 被认为是在附睾转运过程中获得的。然而，具体转移的小 RNA 的身份尚不清楚。在这里，我们利用 Cre/Lox 遗传学产生生殖细胞和附睾特异性 Dgcr8 敲除 (KO) 小鼠，以研究精子 microRNAs (miRNAs) 的动态及其受精后的功能。生殖细胞 Dgcr8 KO 小鼠的睾丸精子中 miRNA 的水平降低了 116 种。令人着迷的是，在附睾转运后，其中 72%的 miRNA 的丰度得到了恢复。相反，来自附睾 Dgcr8 KO 小鼠的精子显示出 27 种 miRNA 水平降低。这种精子中附睾 miRNA 的丢失伴随着由这种精子受精的胚胎中转录组的变化，而通过附睾 miRNA 的显微注射可以挽救这种变化。这些发现最终证明了精子在附睾转运过程中从体细胞获得 miRNA，以及它们随后对胚胎基因表达的调节。
