The State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China; Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, China; Department of Reproductive Medicine, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, China; Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, China.
The State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
Int J Biol Macromol. 2024 May;268(Pt 2):131811. doi: 10.1016/j.ijbiomac.2024.131811. Epub 2024 Apr 25.
It is estimated that 15 % of couples at reproductive age worldwide suffer from infertility, approximately 50 % of cases are caused by male factors. Significant progress has been made in the diagnosis and treatment of male infertility through assisted reproductive technology and molecular genetics methods. However, there is still inadequate research on the underlying mechanisms of gene regulation in the process of spermatogenesis. Guanine-quadruplexes (G4s) are a class of non-canonical secondary structures of nucleic acid commonly found in genomes and RNAs that play important roles in various biological processes. Interestingly, the DEAH-box helicase 36 (DHX36) displays high specificity for the G4s which can unwind both DNA G4s and RNA G4s enzymatically and is highly expressed in testis, thereby regulating multiple cellular functions including transcription, pre-mRNA splicing, translation, telomere maintenance, genomic stability, and RNA metabolism in development and male infertility. This review provides an overview of the roles of G4s and DHX36 in reproduction and development. We mainly focus on the potential role of DHX36 in male infertility. We also discuss possible future research directions regarding the mechanism of spermatogenesis mediated by DHX36 through G4s in spermatogenesis-related genes and provide new targets for gene therapy of male infertility.
据估计，全世界有 15%的育龄夫妇患有不孕症，其中约 50%的病例是由男性因素引起的。通过辅助生殖技术和分子遗传学方法，男性不育的诊断和治疗取得了显著进展。然而，对于精子发生过程中基因调控的潜在机制的研究仍然不足。鸟嘌呤四链体（G4s）是一类常见于基因组和 RNA 中的非经典核酸二级结构，在各种生物学过程中发挥着重要作用。有趣的是，DEAH 盒解旋酶 36（DHX36）对 G4s 具有高度特异性，能够酶促解开 DNA G4s 和 RNA G4s，并且在睾丸中高度表达，从而调节包括转录、前体 mRNA 剪接、翻译、端粒维持、基因组稳定性和 RNA 代谢在内的多种细胞功能在发育和男性不育中。本综述概述了 G4s 和 DHX36 在生殖和发育中的作用。我们主要关注 DHX36 在男性不育中的潜在作用。我们还讨论了通过 G4s 在与精子发生相关的基因中介导 DHX36 对精子发生的可能作用机制，为男性不育的基因治疗提供了新的靶点。
