Oocytes maintain low ROS levels to support the dormancy of primordial follicles

IF 5.4 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS
Shaogang Qin, Xinyue Chi, Zijian Zhu, Chuanhe Chen, Tuo Zhang, Meina He, Meng Gao, Ting Zhao, Jingwen Zhang, Lifan Zhang, Wenying Zheng, Ziqi Chen, Wenji Wang, Bo Zhou, Guoliang Xia, Chao Wang
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Abstract

Primordial follicles (PFs) function as the long-term reserve for female reproduction, remaining dormant in the ovaries and becoming progressively depleted with age. Oxidative stress plays an important role in promoting female reproductive senescence during aging, but the underlying mechanisms remain unclear. Here, we find that low levels of reactive oxygen species (ROS) are essential for sustaining PF dormancy. Compared to growing follicles, oocytes within PFs were shown to be more susceptible to ROS, which accumulates and damages PFs to promote reproductive senescence. Mechanistically, oocytes within PFs were shown to express high levels of the intracellular antioxidant enzyme superoxide dismutase 1 (SOD1), counteracting ROS accumulation. Decreased SOD1 expression, as a result of aging or through the experimental deletion of the Sod1 gene in oocytes, resulted in increased oxidative stress and triggered ferroptosis within PFs. In conclusion, this study identified antioxidant defense mechanisms protecting PFs in mouse ovaries and characterized cell death mechanisms of oxidative stress-induced PF death.

Abstract Image

卵母细胞维持较低的 ROS 水平,以支持原始卵泡休眠
原始卵泡(PFs)是女性生殖的长期储备,在卵巢中处于休眠状态,并随着年龄的增长而逐渐耗竭。在衰老过程中,氧化应激在促进女性生殖衰老方面起着重要作用,但其潜在机制仍不清楚。在这里,我们发现低水平的活性氧(ROS)对维持卵泡刺激休眠至关重要。与生长中的卵泡相比,PFs 内的卵母细胞更容易受到 ROS 的影响,ROS 会积累并破坏 PFs,从而促进生殖衰老。从机理上讲,PFs 内的卵母细胞表达高水平的细胞内抗氧化酶超氧化物歧化酶 1(SOD1),以抵消 ROS 的积累。由于衰老或通过实验性删除卵母细胞中的 Sod1 基因,SOD1 的表达量减少,导致氧化应激增加,并引发 PFs 内的铁变态反应。总之,这项研究确定了保护小鼠卵巢内PF的抗氧化防御机制,并描述了氧化应激诱导PF死亡的细胞死亡机制。
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来源期刊
ACS Biomaterials Science & Engineering
ACS Biomaterials Science & Engineering Materials Science-Biomaterials
CiteScore
10.30
自引率
3.40%
发文量
413
期刊介绍: ACS Biomaterials Science & Engineering is the leading journal in the field of biomaterials, serving as an international forum for publishing cutting-edge research and innovative ideas on a broad range of topics: Applications and Health – implantable tissues and devices, prosthesis, health risks, toxicology Bio-interactions and Bio-compatibility – material-biology interactions, chemical/morphological/structural communication, mechanobiology, signaling and biological responses, immuno-engineering, calcification, coatings, corrosion and degradation of biomaterials and devices, biophysical regulation of cell functions Characterization, Synthesis, and Modification – new biomaterials, bioinspired and biomimetic approaches to biomaterials, exploiting structural hierarchy and architectural control, combinatorial strategies for biomaterials discovery, genetic biomaterials design, synthetic biology, new composite systems, bionics, polymer synthesis Controlled Release and Delivery Systems – biomaterial-based drug and gene delivery, bio-responsive delivery of regulatory molecules, pharmaceutical engineering Healthcare Advances – clinical translation, regulatory issues, patient safety, emerging trends Imaging and Diagnostics – imaging agents and probes, theranostics, biosensors, monitoring Manufacturing and Technology – 3D printing, inks, organ-on-a-chip, bioreactor/perfusion systems, microdevices, BioMEMS, optics and electronics interfaces with biomaterials, systems integration Modeling and Informatics Tools – scaling methods to guide biomaterial design, predictive algorithms for structure-function, biomechanics, integrating bioinformatics with biomaterials discovery, metabolomics in the context of biomaterials Tissue Engineering and Regenerative Medicine – basic and applied studies, cell therapies, scaffolds, vascularization, bioartificial organs, transplantation and functionality, cellular agriculture
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