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[男性不育的分子机制:科学研究的主要方向]

[Molecular mechanisms of male infertility: main directions of scientific research].

作者信息

Galimov S N, Gromenko Yu Yu, Galimova E F, Bodrova E S, Bulygin K V, Litvitsky P F

机构信息

Bashkir StateMedical University, Ufa, Russia.

Medical Center Family, Ufa.

出版信息

Urologiia. 2022 Sep(4):114-117.

Abstract

This review provides up-to-date information on the molecular basis of the pathogenesis of male infertility at the cellular and subcellular levels. The emphasis is on the importance of new next-generation sequencing technologies as a high-performance tool for studying the genome and epigenomic mechanisms, transcriptome, proteome and metabolome of ejaculate, and organs of the reproductive system. This methodology made it possible to identify differentially expressed metabolic and signaling pathways in fertile and infertile men that combine the genotype and phenotype of a particular individual into a single whole. The current ideas about the relationship between oxidative stress and imbalance of redox systems with DNA damage in spermatozoa as the leading mechanism for the development of idiopathic infertility are summarized. The role of miRNAs, methyloma aberrations, deficiency of phospholipase C zeta in spermatozoa in the pathology of fertility is given. Deciphering the molecular profile and molecular phenotypes of infertility as a result of the interaction of genetic and environmental factors is a necessary condition for screening the most informative biomarkers, assessing their stratification potential, and validating new molecules as potential targets for targeted therapy.

摘要

本综述提供了关于男性不育症发病机制在细胞和亚细胞水平上分子基础的最新信息。重点是新一代测序技术作为研究基因组、表观基因组机制、转录组、蛋白质组和射精代谢组以及生殖系统器官的高性能工具的重要性。这种方法使得识别生育和不育男性中差异表达的代谢和信号通路成为可能,这些通路将特定个体的基因型和表型整合为一个整体。总结了目前关于氧化应激与精子中氧化还原系统失衡以及DNA损伤之间关系的观点,这是特发性不育症发展的主要机制。阐述了精子中微小RNA、甲基化异常、磷脂酶C zeta缺乏在生育病理中的作用。解读由于遗传和环境因素相互作用导致的不育症分子特征和分子表型,是筛选最具信息性的生物标志物、评估其分层潜力以及验证新分子作为靶向治疗潜在靶点的必要条件。

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