The dual effects of nanomaterials on sperm and seminal fluid oxidative stress

Abstract

Nanomaterials, due to their unique physicochemical properties, have found widespread applications in biomedical, energy, and environmental fields. Currently, their effects on the male reproductive system are also under investigation. Oxidative stress, a pathological condition resulting from an imbalance between the generation and clearance of reactive oxygen species (ROS), is a critical mechanism affecting male reproductive function. Therefore, this review focuses on the regulatory mechanisms of various nanomaterials on semen oxidative stress, synthesizing literature data and evaluating their effects and molecular underpinnings. Previous studies indicate that nanomaterials exhibit dual effects: some materials (e.g. selenium, cerium dioxide nanoparticles) mimic the activity of superoxide dismutase (SOD) and catalase (CAT), or enhance endogenous antioxidant systems such as glutathione peroxidase (GPx), significantly reducing ROS levels and improving sperm motility, membrane integrity, and DNA stability. Conversely, other materials (e.g., silver nanoparticles, silica nanoparticles) release surface metal ions, activate inflammatory pathways, or impair mitochondrial function, triggering Fenton reactions and excessive ROS accumulation, leading to lipid peroxidation, DNA fragmentation, and reproductive cell apoptosis. Furthermore, the effects of nanomaterials are influenced by their physicochemical characteristics (e.g., size, modification), exposure dose, administration route, and research models. Surface functionalization (e.g., antioxidant loading, polymer coating) can effectively modulate their outcomes. This review emphasizes the need for a careful balance between the antioxidant potential and pro-oxidant risks of nanomaterials in reproductive medicine. Future studies should focus on multi-scale toxicity assessments, standardized model development, and optimized targeted delivery strategies to promote the sustainable application of nanomaterials in male infertility treatment and sperm preservation technologies.

Keywords: DNA fragmentation; Nanomaterial; Oxidative stress; Reactive oxygen species; Semen.

Graphical abstract

Fig. 1

Internal and external factors inducing oxidative stress. A: Schematic illustration of external environmental factors (e.g., psychological stress, ultraviolet radiation, air pollution) triggering oxidative stress. B: Schematic illustration of cellular redox homeostasis. The intracellular reactive oxygen species (ROS) are mainly produced by the mitochondrial electron transport chain (red), endoplasmic reticulum, and NOX complex (green). They are eliminated by antioxidant enzymes such as superoxide dismutase (SOD, yellow), glutathione peroxidase (GPX), and glutathione reductase (GR) (green). (Created with BioRender.com.). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 2

Proportion of types of nanomaterials and related research literature. A: Diversity of nanomaterials (inorganic, organic, carbon-based, etc.) and their characteristics such as size, shape, and surface properties. B: Presentation Method of Literature Evaluation Scheme and the Relevant Percentages of In Vivo and In Vitro Model Studies from 2015 to 2025. C: Distribution of current hotspots in the field of nanomaterial research. Inorganic nanomaterials account for the highest proportion (74 %), while organic materials account for 16 % and carbon-based materials account for 10 %. D: Distribution of the number of papers related to various administration routes (such as oral administration, injection, etc.) in nanomaterial research. E: Mammalian models used in in vivo and in vitro experiments. (Created with BioRender.com.)

Fig. 3

Nano-materials protect the reproductive system by maintaining the oxidation balance. A: CeO₂ NPs achieve the structural mechanism of enzyme-like activity through the regulation of the cerium lattice. Reprinted with permission [60]. Copyright 2015 EPMA Journal. B: CeO₂ NPs can alleviate sperm DNA damage caused by oxidative stress. Reprinted with permission [62]. Copyright 2018 Andrologia. C: VE NE reduces sperm oxidative stress in ram breeding. Reprinted with permission [90]. Copyright 2023 Journal of Animal Science and Biotechnology. D: The influence of VE NE on DNA fragmentation under different temperatures and durations. Reprinted with permission [90]. Copyright 2023 Journal of Animal Science and Biotechnology. (Created with BioRender.com.)

Fig. 4

Nanomaterials induce reproductive toxicity by triggering oxidative stress. A: Research on the biological reduction and stability mechanism of Au NPs. Reprinted with permission [67]. Copyright 2022 Journal of Drug Delivery Science and Technology. B: Au NPs induce the testis to remain in an oxidative stress state for a long time, resulting in abnormal sperm parameters and decreased fertility. Reprinted with permission [117]. Copyright 2023 Toxicology. C: Evaluation experiment of ZnO NPs-induced toxicity in spermatogonial cells. D: The potential biological hazards and influencing mechanisms of ZnO NPs on TM-4 cells and GC2-spd cells. Reprinted with permission [125]. Copyright 2016 Toxicology in Vitro. (Created with BioRender.com.)

Fig. 5

Nanomaterials induce reproductive toxicity through oxidative stress. A: Reveals the dose-dependent reproductive toxicity effect of multi-walled carbon nanotubes (MWCNTs) through in vivo and in vitro comparative experiments. B: The main effect observed after intratesticular injection of IONPs in the mouse model. Reprinted with permission [135]. Copyright 2024 Reproductive Toxicology. C: The reproductive toxicity mechanism of AgNPs on mouse spermatogonial cells and spermatocytes. Reprinted with permission [130]. Copyright 2024 Chemosphere. D: The effects of intravenous injection of IONPs on the testes and epididymis of male ICR mice. Reprinted with permission [108]. Copyright 2022 Journal of Nanobiotechnology. (Created with BioRender.com.)