PIWI-interacting RNAs (piRNAs) are crucial regulators of gene expression in male germ cells. In a study published in Nature Communications, the effect of disrupting piRNA biogenesis on human spermatogenesis was assessed. Analysis of exome data from >2,000 men with infertility led to the identification of biallelic variants in 14 genes related to the piRNA pathway in these men. These variants were associated with various testicular phenotypes, including non-obstructive azoospermia and cryptozoospermia. At a cellular level, dysfunction of piRNA-related genes resulted in reduced piRNA levels and de-repression of transposons in spermatogonia. The reproductive phenotypes of piRNA deregulation varied between mice and humans, highlighting that, although the piRNA pathway is conserved, species-specific research is still necessary. Results from this study show a prominent role of piRNA pathway genes in male infertility, providing potential targets for future investigations.

PIWI 相互作用 RNA (piRNA) 是雄性生殖细胞基因表达的重要调节因子。在《自然通讯》杂志上发表的一项研究中，评估了破坏 piRNA 生物发生对人类精子发生的影响。对 >2,000 名不育男性的外显子组数据进行分析，鉴定出这些男性中与 piRNA 途径相关的 14 个基因中的双等位基因变异。这些变异与各种睾丸表型相关，包括非梗阻性无精症和隐精症。在细胞水平上，piRNA 相关基因的功能障碍导致精原细胞中 piRNA 水平降低和转座子去抑制。 piRNA 失调的生殖表型在小鼠和人类之间存在差异，这凸显出尽管 piRNA 途径是保守的，但物种特异性研究仍然是必要的。这项研究的结果显示了 piRNA 通路基因在男性不育中的重要作用，为未来的研究提供了潜在的目标。