Kobayashi Hiroshi, Imanaka Shogo
Department of Gynecology and Reproductive Medicine, Ms.Clinic MayOne, Kashihara, Japan.
Department of Obstetrics and Gynecology, Nara Medical University, Kashihara, Japan.
J Obstet Gynaecol Res. 2025 Jul;51(7):e16358. doi: 10.1111/jog.16358.
Endometriosis is a chronic gynecological condition characterized by persistent inflammation and frequently associated with dysmenorrhea and infertility. The success rate of assisted reproductive technology (ART) in individuals with endometriosis is often reported to be suboptimal. This review consolidates recent insights into mitochondrial DNA (mtDNA) damage and repair mechanisms in endometriosis patients and examines prospective therapeutic strategies.
For this narrative review, an extensive search of electronic databases was undertaken to identify relevant studies published up to August 31, 2024.
In oocytes and granulosa cells from endometriosis patients, elevated levels of reactive oxygen species (ROS), driven by hypoxia and oxidative stress, contribute to the accumulation of mtDNA mutations. mtDNA repair is primarily dependent on the base excision repair (BER) pathway, mediated by poly(ADP-ribose) polymerase (PARP-1), due to a deficiency in double-strand break repair mechanisms. Upon mtDNA damage, PARP-1 activates single-strand break repair, utilizing nicotinamide adenine dinucleotide (NAD) as a substrate. This process depletes ATP and leads to mitochondrial dysfunction in oocytes and granulosa cells. Such mitochondrial impairment may underlie the reduced efficacy of ART in endometriosis patients. Therapeutic interventions aimed at enhancing mitochondrial function, particularly by increasing mitochondrial NAD levels, represent a promising approach to addressing endometriosis-associated infertility.
mtDNA mutations and defective repair pathways in endometriosis are key contributors to mitochondrial dysfunction, which compromises ART success. This review highlights the potential of mitochondrial function-enhancing therapies as innovative strategies for improving reproductive outcomes in patients with endometriosis.
子宫内膜异位症是一种慢性妇科疾病，其特征为持续性炎症，常伴有痛经和不孕。据报道，子宫内膜异位症患者辅助生殖技术（ART）的成功率往往不理想。本综述整合了对子宫内膜异位症患者线粒体DNA（mtDNA）损伤及修复机制的最新见解，并探讨了潜在的治疗策略。
对于本叙述性综述，我们广泛检索了电子数据库，以识别截至2024年8月31日发表的相关研究。
在子宫内膜异位症患者的卵母细胞和颗粒细胞中，由缺氧和氧化应激驱动的活性氧（ROS）水平升高，导致mtDNA突变的积累。由于双链断裂修复机制存在缺陷，mtDNA修复主要依赖于由聚（ADP - 核糖）聚合酶（PARP - 1）介导的碱基切除修复（BER）途径。mtDNA损伤时，PARP - 1利用烟酰胺腺嘌呤二核苷酸（NAD）作为底物激活单链断裂修复。这一过程消耗ATP，导致卵母细胞和颗粒细胞中的线粒体功能障碍。这种线粒体损伤可能是子宫内膜异位症患者ART疗效降低的原因。旨在增强线粒体功能的治疗干预措施，特别是通过提高线粒体NAD水平，是解决子宫内膜异位症相关不孕问题的一种有前景的方法。
子宫内膜异位症中的mtDNA突变和缺陷的修复途径是线粒体功能障碍的关键因素，这损害了ART的成功率。本综述强调了增强线粒体功能疗法作为改善子宫内膜异位症患者生殖结局的创新策略的潜力。
