Signorini Cinzia, Saso Luciano, Ghareghomi Somayyeh, Telkoparan-Akillilar Pelin, Collodel Giulia, Moretti Elena
Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy.
Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, 00185 Rome, Italy.
Antioxidants (Basel). 2024 Feb 3;13(2):193. doi: 10.3390/antiox13020193.
Infertility represents a significant global health challenge, affecting more than 12% of couples worldwide, and most cases of infertility are caused by male factors. Several pathological pathways are implicated in male infertility. The main mechanisms involved are driven by the loss of reduction-oxidation (redox) homeostasis and the resulting oxidative damage as well as the chronic inflammatory process. Increased or severe oxidative stress leads to sperm plasma membrane and DNA oxidative damage, dysregulated RNA processing, and telomere destruction. The signaling pathways of these molecular events are also regulated by Nuclear factor-E2-related factor 2 (Nrf2). The causes of male infertility, the role of oxidative stress in male infertility and the Keap1-Nrf2 antioxidant pathway are reviewed. This review highlights the regulatory role of Nrf2 in the balance between oxidants and antioxidants as relevant mechanisms to male fertility. Nrf2 is involved in the regulation of spermatogenesis and sperm quality. Establishing a link between Nrf2 signaling pathways and the regulation of male fertility provides the basis for molecular modulation of inflammatory processes, reactive oxygen species generation, and the antioxidant molecular network, including the Nrf2-regulated antioxidant response, to improve male reproductive outcomes.
不孕症是一项重大的全球健康挑战，影响着全球超过12%的夫妇，且大多数不孕症病例是由男性因素导致的。男性不育涉及多种病理途径。主要机制是由氧化还原（redox）稳态失衡及由此产生的氧化损伤以及慢性炎症过程驱动的。氧化应激增加或严重会导致精子质膜和DNA氧化损伤、RNA加工失调以及端粒破坏。这些分子事件的信号通路也受核因子E2相关因子2（Nrf2）调控。本文综述了男性不育的病因、氧化应激在男性不育中的作用以及Keap1-Nrf2抗氧化途径。本综述强调了Nrf2在氧化剂和抗氧化剂平衡中的调节作用，这是与男性生育力相关的机制。Nrf2参与精子发生和精子质量的调节。建立Nrf2信号通路与男性生育力调节之间的联系，为调节炎症过程、活性氧生成以及抗氧化分子网络（包括Nrf2调节的抗氧化反应）以改善男性生殖结局提供了分子基础。
