Khan Ranjha, Azhar Muhammad, Umair Muhammad
Department of Pediatrics, University of California, San Francisco, CA94143, USA.
The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.
Biomedicines. 2024 Dec 15;12(12):2850. doi: 10.3390/biomedicines12122850.
Mammalian fertilization is a complex and highly regulated process that has garnered significant attention, particularly with advancements in assisted reproductive technologies such as in vitro fertilization (IVF). The fusion of egg and sperm involves a sequence of molecular and cellular events, including capacitation, the acrosome reaction, adhesion, and membrane fusion. Critical genetic factors, such as IZUMO1, JUNO (also known as FOLR4), CD9, and several others, have been identified as essential mediators in sperm-egg recognition and membrane fusion. Additionally, glycoproteins such as ZP3 within the zona pellucida are crucial for sperm binding and triggering the acrosome reaction. Recent gene-editing technologies, such as CRISPR/Cas9 and conditional knockout models, have facilitated the functional annotation of genes such as SPAM1 and ADAM family members, further elucidating their roles in capacitation and adhesion. Furthermore, the integration of CRISPR-Cas9 with omics technologies, including transcriptomics, proteomics, and lipidomics, has unlocked new avenues for identifying previously unknown genetic players and pathways involved in fertilization. For instance, transcriptomics can uncover gene expression profiles during gamete maturation, while proteomics identifies key protein interactions critical for processes such as capacitation and the acrosome reaction. Lipidomics adds another dimension by revealing how membrane composition influences gamete fusion. Together, these tools enable the discovery of novel genes, pathways, and molecular mechanisms involved in fertility, providing insights that were previously unattainable. These approaches not only deepen our molecular understanding of fertility mechanisms but also hold promise for refining diagnostic tools and therapeutic interventions for infertility. This review summarizes the current molecular insights into genes orchestrating fertilization and highlights cutting-edge methodologies that propel the field toward novel discoveries. By integrating these findings, this review aims to provide valuable knowledge for clinicians, researchers, and technologists in the field of reproductive biology and assisted reproductive technologies.
哺乳动物受精是一个复杂且受到高度调控的过程，备受关注，尤其是随着体外受精（IVF）等辅助生殖技术的进步。卵子与精子的融合涉及一系列分子和细胞事件，包括获能、顶体反应、黏附以及膜融合。关键的遗传因素，如IZUMO1、JUNO（也称为FOLR4）、CD9等，已被确定为精卵识别和膜融合的重要介导因子。此外，透明带内的糖蛋白如ZP3对于精子结合和触发顶体反应至关重要。近期的基因编辑技术，如CRISPR/Cas9和条件性敲除模型，促进了对SPAM1和ADAM家族成员等基因的功能注释，进一步阐明了它们在获能和黏附中的作用。此外，CRISPR-Cas9与转录组学、蛋白质组学和脂质组学等组学技术的整合，为识别参与受精的先前未知的遗传因子和途径开辟了新途径。例如，转录组学可以揭示配子成熟过程中的基因表达谱，而蛋白质组学则可以识别对获能和顶体反应等过程至关重要的关键蛋白质相互作用。脂质组学通过揭示膜组成如何影响配子融合，增加了另一个维度。这些工具共同作用，能够发现与生育相关的新基因、途径和分子机制，提供了以前无法获得的见解。这些方法不仅加深了我们对生育机制的分子理解，也为完善不孕症的诊断工具和治疗干预带来了希望。本综述总结了目前对协调受精的基因的分子见解，并强调了推动该领域取得新发现的前沿方法。通过整合这些发现，本综述旨在为生殖生物学和辅助生殖技术领域的临床医生、研究人员和技术人员提供有价值的知识。
