Search Results (1,012)

Background/Objectives: Copper is an essential trace element for physiological processes related to reproduction, but its impact on the hypothalamic–pituitary–ovarian (HPOA) axis and its specific mechanism remain unclear. Methods: In vivo study: 21-day-old female Sprague Dawley (SD) rats were randomly assigned to five groups (n = 10 per group), with all groups fed a basal diet and supplemented with CuSO₄·5H₂O to achieve copper ion concentrations of 0, 15, 30, 45, or 60 mg/kg in the diet. During the second phase of proestrus, blood samples, hypothalamic tissues, pituitary tissues, and ovarian tissues were collected. In vitro study: Primary mixed hypothalamic neurons were isolated and cultured from fetal SD rats on embryonic day 17. After identification by NSE immunofluorescence staining, six copper ion concentration groups (0, 15.6, 31.2, 46.8, 62.4, and 78 μmol/L) were established. The optimal copper concentration for cell viability and GnRH secretion was screened using CCK-8 assay (Sangon, Shanghai, China) and ELISA (Mlbio, Shanghai, China). On this basis, the cells were treated with different concentrations of PKC agonist (PMA) and PKC inhibitor (chelerythrine). Cell viability was evaluated by CCK-8 assay, the expression level of PKC was detected by Western blot, and the optimal concentration with no obvious toxicity was selected for subsequent mechanism research. Results: Dietary copper dose-dependently regulated rat puberty onset; the 45 mg/kg copper group had the earliest onset, and showed significantly increased levels of reproduction-related hormones (GnRH, FSH, LH, E₂) in serum and HPOA axis. Hypothalamic transcriptomics revealed significantly enriched GnRH signaling pathways and GABAergic synaptic pathways. Mechanistically, this copper dose upregulated hypothalamic KISS-1, GPR54, and PKC (mRNA/protein), and downregulated GABA/GABA-R. Adding 46.8 μmol/L copper (as Cu²⁺, equivalent to optimal in vivo level) could activate the KISS-1/GPR54-GnRH system in hypothalamic neurons; regulating PKC activity could synchronously affect the expression of KISS-1, GPR54, GnRH, and GABA/GABA-R, with additional copper enhancing this effect in vitro experiments. Conclusions: This study demonstrates for the first time that dietary copper at 45 mg/kg promotes puberty onset in SD rats. The mechanism involves activation of the hypothalamic PKC pathway, which inhibits GABAergic neurotransmission while activating the KISS-1/GPR54-GnRH system, thereby enhancing HPOA axis activity and gonadotropin secretion. Full article

Glyphosate, a widely used non-selective herbicide, has been a subject of intense scientific debate due to its environmental persistence and potential health risks. This review examines glyphosate’s mechanisms of action, its effects on crop production, and its broader environmental impact, including soil degradation, water contamination, and biodiversity loss. Furthermore, it examines the expanding body of research linking glyphosate exposure to various human health concerns, including metabolic, neurological, reproductive, and oncological disorders. The review also assesses glyphosate’s role in hindering the achievement of the Sustainable Development Goals (SDGs), particularly those related to food security, health, access to clean water, and the protection of marine ecosystems. Finally, potential alternatives to glyphosate-based weed control, including organic and non-chemical methods, are discussed to promote sustainable agricultural practices that balance productivity with ecological and public health considerations. The evidence reviewed highlights glyphosate’s pervasive presence across ecosystems and its potential to disrupt both environmental and human health. The findings underscore the urgent need to regulate glyphosate use, prioritize soil and water protection, and accelerate the transition toward sustainable, low-toxicity weed management strategies that align with global sustainability objectives. Full article

Nanoplastics have emerged as widespread environmental contaminants with toxicological properties that differ from those of microplastics. While existing reviews often examine their effects on specific organisms, they rarely provide direct comparisons with microplastics. This review aims to comprehensively assess the toxic effects of nanoplastics on animals, with a comparative perspective highlighting their distinctions from microplastics. In mammals, nanoplastics cross the blood–brain barrier and induce oxidative stress, neuroinflammation, mitochondrial dysfunction, and synaptic disruption, with consequences ranging from cognitive impairment to Parkinson’s disease-like neurodegeneration. They also impair liver, kidney, intestinal, pancreatic, and reproductive function, with evidence of transgenerational toxicity. In aquatic organisms such as fish, crustaceans, bivalves, and aquatic invertebrates, nanoplastics compromise growth, immunity, reproduction, and metabolism, while in terrestrial invertebrates they cause gut toxicity, mitochondrial damage, immune suppression, and heritable defects. Across taxa, the dominant mechanisms involve oxidative stress, apoptosis, inflammation, and interference with metabolic and signaling pathways. Comparisons with microplastics reveal that while both particle types are harmful, nanoplastics generally exert stronger and more systemic effects due to higher bioavailability, cellular uptake, and molecular reactivity. Microplastics primarily impose mechanical stress, whereas nanoplastics disrupt cellular homeostasis at lower exposure levels, often acting at the subcellular level. Evidence also indicates size-, surface chemistry-, and concentration-dependent effects, with smaller and functionalized nanoplastics exhibiting heightened toxicity. Despite growing knowledge, significant gaps remain in cross-size comparative studies, long-term and multigenerational assessments, trophic transfer analyses, and investigations involving environmentally derived nanoplastics. Addressing these gaps is critical for advancing ecological risk assessment and developing mitigation strategies against plastic pollution. Full article

Aquatic ecosystems are increasingly threatened by multiple anthropogenic stressors, notably climate change and pollution by pharmaceuticals. Global warming is predicted to raise water temperatures by 2–5 °C by the end of the century. As ectotherms, fish are particularly vulnerable due to limited thermal tolerance and temperature-dependent physiology. Pharmaceuticals are introduced into aquatic systems at concentrations ranging from ng·L⁻¹ to µg·L⁻¹, including widely prescribed classes such as antibiotics, hormones, analgesics, antifungals, and neuropsychiatric drugs. This narrative review synthesizes experimental evidence on the interactive effects of warming and pharmaceutical exposure in fish. Thirty-nine peer-reviewed studies published since 2005 were analyzed. The findings indicate that higher temperatures often exacerbate pharmaceutical-induced toxicity, altering oxidative stress, metabolism, reproduction, and behavior. Antibiotic-focused studies showed temperature-dependent acceleration of absorption, distribution, metabolism, and excretion, with shorter half-lives and reduced tissue persistence at higher temperatures. Estrogenic hormones and antifungals have been shown to interact with thermal regimes, disrupting reproductive physiology and skewing sex ratios, particularly in species exhibiting temperature-dependent sex determination. Neuropsychiatric drugs exhibited altered uptake and metabolism under warming conditions, resulting in increased brain bioaccumulation and behavioral alterations affecting ecological fitness. Analgesics and anti-inflammatories remain understudied despite their widespread use, with evidence suggesting synergistic effects on oxidative stress at elevated temperatures. Significant research gaps persist regarding chronic exposures, early developmental stages, ecologically relevant temperature scenarios, and underrepresented or absent drug classes, such as hypolipidemic drugs. Ultimately, broader and integrated approaches are needed to better understand and predict the ecological risks of pharmaceutical pollution in a warming world. Full article

Triclosan (TCS), a widely used environmental antimicrobial agent, poses potential risks to female reproductive health, yet its toxic effects on oocyte maturation remain inadequately characterized. In this study, we established an in vitro maturation (IVM) model of porcine oocytes to investigate TCS-induced meiotic impairment and to evaluate the rescuing effects of melatonin (MT), an endogenous indoleamine with potent antioxidant and anti-apoptotic activities. Our results demonstrated that TCS exposure significantly disrupted oocyte maturation, as evidenced by suppressed polar body extrusion and compromised cumulus expansion. Furthermore, TCS triggered early apoptosis. Proteomic analysis revealed that the p53 signaling pathway was significantly dysregulated by TCS exposure. Notably, co-treatment with MT during IVM effectively restored meiotic progression, attenuated apoptosis, and rebalanced the disrupted proteomic profile. Mechanistic investigation, validated by Western blotting, confirmed that TCS upregulated p53 and downregulated its downstream cell cycle effector CCNB1 while concurrently altering the ratio of apoptosis-related proteins BAX/BCL-2. Melatonin treatment effectively normalized the expression of these key proteins (p53, CCNB1, BAX, and BCL-2). These findings illustrate that MT rescues TCS-impaired oocyte quality through p53-dependent suppression of apoptosis and restoration of meiotic progression, providing new insights into potential strategies for mitigating environmental pollutant-induced reproductive damage. Full article

Heavy metal and metalloid stress, particularly from toxic elements like cadmium (Cd), poses a growing threat to plant ecosystems, crop productivity, and global food security. Elevated concentrations of these contaminants can trigger cytotoxic and genotoxic effects in plants, severely impairing growth, development, and reproduction. In recent years, epigenetic mechanisms have emerged as crucial regulators of plant responses to heavy metal stress, offering novel insights and strategies for enhancing plant resilience in contaminated environments. This review synthesises current advances in the field of plant epigenetics, focusing on key modifications such as DNA methylation, histone acetylation and remodelling, chromatin dynamics, and small RNA-mediated regulation. These processes not only influence gene expression under metal-induced stress but also hold promise for long-term adaptation through transgenerational epigenetic memory. Recent developments in high-throughput sequencing and functional genomics have accelerated the identification of epigenetic markers associated with stress tolerance, enabling the integration of these markers into breeding programs and targeted epigenome editing strategies. Special attention is given to cadmium stress responses, where specific epigenetic traits have been linked to enhanced tolerance. As plant epigenomic research progresses, its application in sustainable agriculture becomes increasingly evident offering environmentally friendly solutions to mitigate the impact of heavy metal pollution. This review provides a foundation for future research aimed at leveraging epigenetic tools to engineer crops capable of thriving under metal stress, thereby contributing to resilient agricultural systems and sustainable food production. Full article

The pervasive contamination of microplastics and nanoplastics (MNPs) in livestock and poultry production systems represent a critical threat to animal health, productivity, and food safety. This review systematically evaluates the potential of curcumin, a natural polyphenol from Curcuma longa, to mitigate MNP-induced toxicity, drawing on evidence from 25 preclinical studies (2014–September 2025). We highlight that curcumin exerts broad-spectrum, dose-dependent protection primarily through a dual mechanism: the preventive activation of the Nrf2/ARE antioxidant pathway and the therapeutic suppression of NF-κB-driven inflammation. These actions collectively ameliorate oxidative stress, restore metabolic homeostasis (e.g., via the gut–liver axis), and reverse histopathological damage across key organs, including the liver, kidneys, and reproductive tissues. A major translational insight is the significant species-specific variation in curcumin bioavailability, which is substantially higher in poultry than in ruminants, necessitating the development of tailored delivery systems such as nanoencapsulation. While the preclinical data are compelling, translating these findings into practice requires robust clinical trials to establish standardized, safe, and effective dosing regimens for food-producing animals. This review concludes that curcumin presents a promising, sustainable phytogenic strategy to enhance the resilience of livestock and poultry systems against MNP pollution, directly contributing to the One Health goals of safeguarding animal welfare, food security, and environmental sustainability. Full article

Nanoplastics are pervasive contaminants that adversely affect male reproductive function, yet the molecular basis of polystyrene nanoplastic (PS-NP) toxicity in immature testes and effective preventive strategies remain unclear. Here, male mice (postnatal days 22–35, PND 22–35) and TM3 Leydig cells were exposed to graded PS-NPs, followed by transcriptomic profiling to identify differentially expressed genes (DEGs). Candidate therapeutics were prioritized using Connectivity Map (CMap) analysis and molecular docking, and protein interactions were examined by co-immunoprecipitation (Co-IP). PS-NPs accumulated in immature testes, eliciting excessive reactive oxygen species (ROS) and activation of NF-κB. These events coincided with the downregulation of steroidogenic enzymes (CYP11A1 and StAR) and disruption of testicular microarchitecture. In TM3 cells, PS-NPs suppressed testosterone synthesis in a concentration-dependent manner; this effect was fully reversed by pretreatment with N-acetylcysteine (NAC) or Bay 11-7082. Co-IP demonstrated p65–steroidogenic factor-1 (SF-1) binding consistent with formation of a transcriptional repressor complex targeting steroidogenic genes. CMap and docking analyses nominated parthenolide (PTL) as a candidate inhibitor of NF-κB nuclear translocation (predicted binding affinity, −6.585 kcal/mol), and PTL mitigated PS-NP-induced impairment of testosterone synthesis in vitro. Collectively, these data indicate that PS-NPs disrupt testosterone biosynthesis in immature testes through the ROS/NF-κB/p65–SF-1 axis, while PTL emerges as a candidate small molecule to counter nanoplastic-associated reproductive toxicity. These findings underscore translational relevance and support future evaluation under chronic low-dose exposure conditions, including in vivo validation of PTL efficacy, pharmacokinetics, and safety. Full article

Polystyrene microplastics (PS-MPs) are microplastic particles produced during plastic manufacturing and environmental degradation, accumulating over time and entering ecosystems through various pathways, ultimately affecting organisms and inducing toxic effects. Current research on the impact of PS-MPs on mammalian oocyte quality, along with potential preventive mechanisms and strategies to mitigate toxicity, remains limited. This study investigates the effects of antioxidant melatonin on oocyte quality in the presence of PS-MPs, focusing on their influence on oocyte meiotic maturation and embryonic developmental potential. PS-MPs at a concentration of 30 μg/mL significantly impaired first polar body extrusion and reduced the success rate of parthenogenetic activation of mature oocytes in vitro. Furthermore, exposure to PS-MPs exacerbated oxidative stress, mitochondrial dysfunction, apoptosis, and autophagy impairment. Additionally, PS-MPs exposure led to a reduction in antioxidant gene expression and an increase in apoptosis-related gene expression in porcine oocytes. Immunofluorescence assays revealed that PS-MPs may induce oxidative stress, mitochondrial damage, and inflammation through the NF-KB/Nrf2/JNK MAPK signaling pathway crosstalk. Further investigation demonstrated that melatonin supplementation alleviated the toxic effects of PS-MPs exposure, offering potential as a therapeutic approach for mitigating PS-MP-induced reproductive toxicity and preserving oocyte quality. Full article

A low-scale Food Waste Compost (FWC1), characterized by optimal physic-chemical parameters and high organic matter percentages, was used as a fertilizer and a bio-stimulant for vegetable plants. Groups of treated plants were inoculated with active juveniles of root-knot nematodes to detect the effect on plant defense. Optimal amounts of compost mixed with soil increased plant biomass 30% compared to untreated plants. Moreover, when plants were inoculated, treated roots contained about 50% less sedentary forms (SFs) of nematodes and a lower reproduction rate of the parasites than untreated plants. Although the performance of FWC1 as defense activator was similar to other microbiome-generating commercial formulations, the compost was found to be the best fertilizer in both un- and inoculated plants. Diffuse root colonization by arbuscular mycorrhizal fungi (AMF) was observed after treatments with FWC1. FWC1 water extracts did not show any toxic effect on living nematode juveniles. Expression of the marker gene of immune response PR4b was found to be 3–5-fold higher in the roots of inoculated plants treated with FWC1 with respect to untreated plants, thus indicating that FWC1 primes plants against RKNs (root-knot nematodes, Meloidogyne incognita (Kofoid White) Chitw). Data are reported to associate immunization of plants with mycorrhization occurring in FWC1-treated plants. The proposed compost is indicated as having optimal performance both as a bio-fertilizer and a bio-stimulant. Full article

Endometriosis is a common gynecological condition that affects fertility in many women of reproductive age worldwide. This multifaceted disease exhibits a pathogenesis characterized by hormonal and immune system dysregulations, alongside increased angiogenic activity within the peritoneum. The aberrant proliferation of endometrial tissue outside the uterus is associated with vascularization in ectopic endometriotic lesions. Consequently, RNA interference (RNAi)-based angiogenic therapies targeting the VEGFA gene present a promising strategy for the treatment of endometriosis. To ensure the efficacy of RNAi-based therapy, it is critical to develop carriers capable of precisely delivering small interfering RNA (siRNA) to target cells. Additionally, the instability of polyplexes in vivo must be regarded as a pivotal aspect influencing the success of non-viral delivery. In this study, we introduce ternary polyplexes comprising siRNA and a carrier derived from an arginine–histidine-rich peptide, which is further coated with a glutamate–histidine-rich polymer modified using an SDF-1 chemokine-derived ligand for targeting CXCR4-expressing cells. The physicochemical characteristics of the siRNA-polyplexes, along with cellular toxicity and GFP gene silencing efficacy, were assessed in vitro. The anti-angiogenic potential of anti-VEGFA siRNA-polyplexes was evaluated by measuring the size of endometrial lesions, conducting immunohistochemical staining, and analyzing VEGFA gene expression. For in vivo experiment, a rat model of endometriosis induced by subcutaneous auto-transplantation of uterine tissue was utilized. A significant reduction in the growth of endometriotic implants and silencing of VEGFA gene expression was observed when compared to the saline-treated control group. The results of this study strongly suggest that the developed ternary polyplexes have significant potential as an efficient tool for the development of anti-angiogenic RNAi-based therapies for endometriosis. Full article

Nickel (Ni), a heavy metal with extensive industrial applications, poses significant ecological impacts and health risks due to its persistence and bioaccumulation. Although toxicological data in mammals and plants are well established, its effects on invertebrate models remain insufficiently explored, especially at environmentally relevant concentrations. This study systematically evaluated the toxicity of Ni²⁺ on Caenorhabditis elegans, integrating phenotypic assays with transcriptomic profiling to assess impacts on growth, reproduction, neuromuscular function, lifespan, and aging. Ni exposure induced dose-dependent developmental delays. After exposure to 80 μg/L Ni²⁺ for 72 h, the proportion of L1-stage nematodes increased 3.8-fold compared to the control group. Similarly, exposure to 80 µg/L Ni²⁺ reduced the reproductive capacity of nematodes to 88.5% of that in the control group. Transcriptomic analysis identified 2235 differentially expressed genes (DEGs) after 8 μg/L of Ni²⁺ exposure, while the worms exposed to 0.8 μg/L of Ni²⁺ exhibited a total of 249 DEGs. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses highlighted collagen metabolism defects, fatty acid-related metabolism, amino acid-related biosynthesis disruption, and lysosomal dysfunction, correlating with cuticle integrity loss, energy metabolism abnormality, and feeding behavior change, and indirectly lead to delayed growth development and lipofuscin accumulation. The latter is usually regarded as a reliable indicator of aging, suggesting that exposure to Ni poses a risk of accelerating aging in nematodes. This study provides critical insights into the ecological risks of Ni pollution. Full article

Acetamiprid (ACE), a widely used neonicotinoid insecticide, has raised concerns due to its potential reproductive toxicity. While its adverse effects on animal reproductive systems have been documented, the impact of ACE on mammalian oocytes remains poorly understood. This study aimed to investigate the potential effects of ACE exposure on porcine oocytes and evaluate whether alpha-tocopherol (α-TOC), a fat-soluble antioxidant, could alleviate ACE-induced oocyte damage. Porcine cumulus oocyte complexes (COCs) were exposed to ACE alone or co-treated with α-TOC for 44 h during in vitro maturation. ACE exposure significantly reduced the first polar body (PB1) excretion rate, arrested meiotic progression, and disrupted spindle assembly in porcine oocytes. Furthermore, ACE impaired mitochondrial function, evidenced by decreased mitochondrial membrane potential (MMP), while increasing intracellular reactive oxygen species (ROS) accumulation and lipid peroxidation (LPO). Additionally, ACE exposure induced intracellular iron overload and dysregulated ferroptosis-related genes, downregulating solute carrier family 7 member 11 (SLC7a11) and glutathione peroxidase 4 (GPX4) while upregulating transferrin receptor 1 (TfRC) and acyl-CoA synthetase long-chain family member 4 (ACSL4), contributing to the occurrence of oocyte ferroptosis. Notably, α-TOC co-treatment effectively alleviate oxidative stress and lipid peroxidation, thereby protecting oocytes from ACE-induced ferroptosis. Collectively, these findings indicate that oxidative stress-mediated ferroptosis may be a major contributing pathway through which ACE impairs oocyte maturation and suggest that α-tocopherol may serve as a protective agent against ACE-induced oocyte damage. Full article

Polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic disorder affecting 6–20% of women of reproductive age, manifesting through hyperandrogenism, ovulatory dysfunction, insulin resistance, and diverse metabolic derangements. Increasing evidence highlights the contribution of environmental factors, particularly endocrine-disrupting chemicals (EDCs), to PCOS susceptibility and severity. Sunscreen ultraviolet (UV) filters such as oxybenzone (benzophenone-3) and octinoxate (ethylhexyl methoxycinnamate) are widely used EDCs with established systemic absorption and biomonitoring evidence in human populations. Their endocrine-disrupting potential encompasses estrogenic and anti-androgenic activity, interference with steroidogenic enzymes, modulation of thyroid hormone, induction of oxidative stress, and epigenetic reprogramming, all of which are mechanistic pathways that overlap with PCOS pathophysiology. This evidence-based study critically appraises the evidence linking oxybenzone and octinoxate exposures to ovarian endocrinology, with a PCOS-specific focus. Human exposure patterns, pharmacokinetics, and regulatory perspectives are summarized alongside preclinical and in vitro data implicating these filters in ovarian dysfunction. Mechanistic intersections with PCOS include hyperandrogenism, disrupted folliculogenesis, oxidative stress-adipokine imbalance, and potential impairment of vitamin D signaling. Although epidemiological studies directly addressing PCOS outcomes remain sparse, the convergence of toxicological evidence with known endocrine vulnerabilities in PCOS underscores a need for targeted investigation. By mapping exposure pathways and mechanistic disruptions, this appraisal emphasizes the translational relevance of UV filter toxicity in the context of PCOS. It advocates for PCOS-specific biomonitoring cohorts, mechanistic studies, and regulatory consideration of reproductive endpoints while balancing the dermatological benefits of photoprotection against reproductive risks. Full article

Cadmium (Cd) is a recognized environmental contaminant, present in soil, water, and food, which has been reported to cause male reproductive damage in vivo and vitro. Selenium-enriched rapeseed flowering stalks exhibit protective effects against Cd-induced reproductive damage, yet the bioactive components and underlying mechanisms remain unclear. We optimized the process of obtaining the crude extract (CE) via single-factor experiments. Subsequent bioassay-guided fractionation identified the water extract (WE) as significantly more effective in alleviating Cd-induced cytotoxicity compared to the petroleum ether extract, ethyl acetate extract, and n-butanol extract. High-performance liquid chromatography–inductively coupled plasma mass spectrometry (HPLC-ICP-MS) analysis revealed that WE contained the highest contents of methylselenocysteine (MeSeCys) and selenocystine (SeCys₂) among four fractions. Both MeSeCys and SeCys₂ exhibited protective effects against Cd-induced cytotoxicity. To further elucidate the underlying mechanisms, network pharmacology, RNA-Seq, qPCR, and Western blotting analysis were employed. The results revealed that WE exhibited good free radical scavenging capabilities, and the protective mechanisms of WE, MeSeCys, and SeCys₂ against Cd-induced cytotoxicity were related to a reduction in oxidative damage, the inhibition of the ERK/p38 MAPK signaling pathway, and the suppression of cell cycle arrest, inflammation, and apoptosis triggered by Cd exposure. Collectively, these findings suggest that selenium-enriched rapeseed flowering stalks may serve as a promising dietary supplement in the prevention of Cd-induced reproductive toxicity. Full article