Epididymal acquired sperm microRNAs modify post-fertilization embryonic gene expression.

IF 7.5 1区 生物学 Q1 CELL BIOLOGY
Natalie A Trigg, Colin C Conine
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Abstract

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.

Abstract Image

附睾获得的精子 microRNA 可改变受精后胚胎基因的表达。
精子小 RNA 已成为影响胚胎发生和后代健康的重要非遗传因素。精子小 RNA 的一个子集被认为是在附睾转运过程中获得的。然而,转移的特定小 RNA 的身份仍不清楚。在这里,我们采用Cre/Lox遗传学方法产生生殖系和附睾特异性Dgcr8基因敲除(KO)小鼠,研究精子microRNA(miRNA)的动态及其受精后的功能。生殖系 Dgcr8 KO 小鼠睾丸精子中的 116 种 miRNA 水平降低。令人震惊的是,在附睾转运后,这些 miRNA 中 72% 的丰度得到了恢复。相反,附睾 Dgcr8 KO 小鼠的精子中 27 个 miRNA 水平降低。精子中附睾 miRNA 的这种损失伴随着由这种精子受精的胚胎转录组的变化,而附睾 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了 miRNAs,并随后对胚胎基因表达进行了调控。
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来源期刊
Cell reports
Cell reports CELL BIOLOGY-
CiteScore
13.80
自引率
1.10%
发文量
1305
审稿时长
77 days
期刊介绍: Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.
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