Tracing refractile body biogenesis in human oocytes: the role of lysosomes and mitochondria.

IF 2 4区医学 Q3 ANDROLOGY

Systems Biology in Reproductive Medicine Pub Date : 2026-12-01 Epub Date: 2026-01-16 DOI:10.1080/19396368.2025.2610348

Yuto Aoki, Xingqiang Wei, Mikiya Nakatsuka, Junko Otsuki

{"title":"Tracing refractile body biogenesis in human oocytes: the role of lysosomes and mitochondria.","authors":"Yuto Aoki, Xingqiang Wei, Mikiya Nakatsuka, Junko Otsuki","doi":"10.1080/19396368.2025.2610348","DOIUrl":null,"url":null,"abstract":"<p><p>Refractile bodies (RBs) in human primordial oocytes may represent a lysosomal mechanism of cellular waste management independent of hormonal stimulation or age. This observational study investigated the ultrastructural features and molecular characteristics of refractile bodies (RBs) in human primordial oocytes, focusing on the involvement of lysosomes, autophagy, and mitochondria. Ovarian tissues were obtained from 34 individuals undergoing oophorectomy as part of female-to-male gender-affirming surgery, with no clinical interventions applied. Using fluorescence microscopy, immunocytochemistry, and transmission electron microscopy (TEM), we found large RBs (>5 μm) in all individuals, with no correlation to age. RBs exhibited strong LysoTracker fluorescence, indicating acidic content. LC3, but not RAB7, colocalized with RBs, suggesting incomplete autophagic processing. TEM revealed lysosomal vesicles, mitochondrial remnants, and lipid-rich structures within RBs, some partially enclosed by isolation membranes. These features support a model in which RBs transition from passive lipid accumulation to autophagy-driven remodeling in a size-dependent manner. RBs displayed lipofuscin-like characteristics and are likely formed through lysosomal and mitophagic pathways. Their formation appears to involve both canonical and non-canonical autophagic mechanisms, independent of age or hormonal stimulation. A limitation of this study is its observational nature without functional validation.</p>","PeriodicalId":22184,"journal":{"name":"Systems Biology in Reproductive Medicine","volume":"72 1","pages":"73-86"},"PeriodicalIF":2.0000,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Systems Biology in Reproductive Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/19396368.2025.2610348","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/1/16 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"ANDROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Refractile bodies (RBs) in human primordial oocytes may represent a lysosomal mechanism of cellular waste management independent of hormonal stimulation or age. This observational study investigated the ultrastructural features and molecular characteristics of refractile bodies (RBs) in human primordial oocytes, focusing on the involvement of lysosomes, autophagy, and mitochondria. Ovarian tissues were obtained from 34 individuals undergoing oophorectomy as part of female-to-male gender-affirming surgery, with no clinical interventions applied. Using fluorescence microscopy, immunocytochemistry, and transmission electron microscopy (TEM), we found large RBs (>5 μm) in all individuals, with no correlation to age. RBs exhibited strong LysoTracker fluorescence, indicating acidic content. LC3, but not RAB7, colocalized with RBs, suggesting incomplete autophagic processing. TEM revealed lysosomal vesicles, mitochondrial remnants, and lipid-rich structures within RBs, some partially enclosed by isolation membranes. These features support a model in which RBs transition from passive lipid accumulation to autophagy-driven remodeling in a size-dependent manner. RBs displayed lipofuscin-like characteristics and are likely formed through lysosomal and mitophagic pathways. Their formation appears to involve both canonical and non-canonical autophagic mechanisms, independent of age or hormonal stimulation. A limitation of this study is its observational nature without functional validation.

查看原文本刊更多论文

追踪人卵母细胞的折射体生物发生：溶酶体和线粒体的作用。

人类原始卵母细胞中的折射体（RBs）可能代表了一种独立于激素刺激或年龄的细胞废物处理溶酶体机制。本观察性研究探讨了人类原始卵母细胞中折射体（refractile bodies, RBs）的超微结构特征和分子特征，重点研究了溶酶体、自噬和线粒体的参与。从34个接受卵巢切除术的个体中获得卵巢组织，作为女性对男性性别确认手术的一部分，没有应用临床干预。通过荧光显微镜、免疫细胞化学和透射电子显微镜（TEM），我们发现所有个体的大RBs （bbb50 μm）与年龄无关。RBs表现出强烈的LysoTracker荧光，表明其酸性含量。LC3，而不是RAB7，与RBs共定位，提示自噬过程不完全。透射电镜显示，RBs内有溶酶体囊泡、线粒体残体和富含脂质的结构，其中一些被隔离膜部分封闭。这些特征支持一个模型，在这个模型中，RBs以尺寸依赖的方式从被动脂质积累转变为自噬驱动的重塑。RBs表现出脂褐素样特征，可能通过溶酶体和有丝分裂途径形成。它们的形成似乎涉及规范和非规范的自噬机制，独立于年龄或激素刺激。这项研究的一个局限性是它的观察性质，没有功能验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Systems Biology in Reproductive Medicine 医学-男科学

CiteScore

4.30

自引率

4.20%

发文量

审稿时长

>12 weeks

期刊介绍： Systems Biology in Reproductive Medicine, SBiRM, publishes Research Articles, Communications, Applications Notes that include protocols a Clinical Corner that includes case reports, Review Articles and Hypotheses and Letters to the Editor on human and animal reproduction. The journal will highlight the use of systems approaches including genomic, cellular, proteomic, metabolomic, bioinformatic, molecular, and biochemical, to address fundamental questions in reproductive biology, reproductive medicine, and translational research. The journal publishes research involving human and animal gametes, stem cells, developmental biology and toxicology, and clinical care in reproductive medicine. Specific areas of interest to the journal include: male factor infertility and germ cell biology, reproductive technologies (gamete micro-manipulation and cryopreservation, in vitro fertilization/embryo transfer (IVF/ET) and contraception. Research that is directed towards developing new or enhanced technologies for clinical medicine or scientific research in reproduction is of significant interest to the journal.