用于生育的基因组编辑:释放CRISPR/Cas9在解决男性不育问题上的潜力——一篇综述
Genome Editing for Fertility: Unlocking the Promise of CRISPR/Cas9 in Addressing Male Infertility - A Narrative Review.
作者信息
Kumar Naina
机构信息
Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, Bibinagar, Hyderabad, Telangana, 508126, India.
出版信息
Reprod Sci. 2025 Sep 2. doi: 10.1007/s43032-025-01972-x.
Male infertility remains a significant global reproductive health challenge, frequently attributed to genetic mutations impairing spermatogenesis and sperm function. This narrative review aims to explore the genetic and molecular underpinnings of male infertility and evaluate the emerging role of Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-associated protein 9 (CRISPR/Cas9) genome editing as a diagnostic and therapeutic tool, while addressing its associated ethical, technical, and safety considerations. A Comprehensive literature search was conducted across PubMed, Scopus, Web of Science databases, covering studies published between September 1992 and April 2025. Keywords included "male infertility," "genetic causes of male infertility," "genome editing," "CRISPR/Cas9 and male infertility," "genome editing in male reproduction," "ethical concerns of CRISPR," and "future fertility treatments." Eligible studies focused on genetic correction strategies, spermatogonial stem cell applications, off-target effects, mosaicism, and ethical implications of gene editing. The review synthesizes current knowledge on genetic and epigenetic etiologies of male infertility. It discusses the therapeutic potential of CRISPR/Cas9 in correcting these defects and restoring fertility in preclinical models. Critical challenges, including off-target gene editing, germline mosaicism, long-term safety, and ethical debates surrounding human germline modification, were examined. The review also considers future advancements in genome editing and artificial sperm development. CRISPR/Cas9 represents a transformative platform in reproductive medicine with promising implications for treatment of genetically linked male infertility. However, its clinical translation demands rigorous validation, transparent ethical deliberation, and robust regulatory frameworks. Future innovations combining genome editing, regenerative biology, and precision diagnostics may revolutionize fertility care, but must proceed with caution to ensure safety, efficacy, and ethical integrity.
男性不育仍然是一个重大的全球生殖健康挑战,通常归因于损害精子发生和精子功能的基因突变。本叙述性综述旨在探讨男性不育的遗传和分子基础,并评估成簇规律间隔短回文重复序列-CRISPR相关蛋白9(CRISPR/Cas9)基因组编辑作为一种诊断和治疗工具的新兴作用,同时探讨其相关的伦理、技术和安全考虑因素。在PubMed、Scopus、科学网数据库中进行了全面的文献检索,涵盖1992年9月至2025年4月发表的研究。关键词包括“男性不育”、“男性不育的遗传原因”、“基因组编辑”、“CRISPR/Cas9与男性不育”、“男性生殖中的基因组编辑”、“CRISPR的伦理问题”和“未来的生育治疗”。符合条件的研究集中在基因校正策略、精原干细胞应用、脱靶效应、嵌合体以及基因编辑的伦理影响。该综述综合了关于男性不育的遗传和表观遗传病因的当前知识。它讨论了CRISPR/Cas9在纠正这些缺陷和恢复临床前模型中的生育能力方面的治疗潜力。研究了关键挑战,包括脱靶基因编辑、种系嵌合体、长期安全性以及围绕人类种系修饰的伦理辩论。该综述还考虑了基因组编辑和人工精子发育的未来进展。CRISPR/Cas9代表了生殖医学中的一个变革性平台,对治疗与基因相关的男性不育具有广阔前景。然而,其临床转化需要严格的验证、透明的伦理审议和强大的监管框架。未来将基因组编辑、再生生物学和精准诊断相结合的创新可能会彻底改变生育治疗,但必须谨慎进行,以确保安全性、有效性和伦理完整性。