摘要Non-obstructive azoospermia(NOA),the lack of sperm in the ejac-ulate due to failure of spermatogenesis,can result from a variety of diverse factors,with genetic factors accounting for-30％of NOA cases,including chromosomal aberrations,Y-chromosome microde-letions,and monogenic variants(Tang et al.,2022).More than 2000 genes are known to participate in spermatogenesis,and＞400 genes specifically linked to azoospermia have been identified through studies in mouse models(Krausz and Riera-Escamilla,2018).Howev-er,relatively few genes associated with azoospermia in mice have been verified in humans.In recent years,considerable research efforts have been committed to screening genetic mutations in piRNA pathway genes that contribute to human infertility(Wang et al.,2023),resulting in the identification of a number of specific single-nucleotide polymorphisms in PIWI proteins,especially D-box muta-tions in PIWIL1(Gou et al.,2021).Pathogenic variants of the piRNA trimming factor PNLDC1 have been reported by three independent groups(Nagirnaja et al.,2021;Wang et al.,2022).These studies have thus firmly linked piRNA-processing enzymes to infertility in men.