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Toxins · 2024 ·Vol. 16 ·期 3 ·121 · IF 3.9

Alleviative Effect of Rutin on Zearalenone-Induced Reproductive Toxicity in Male Mice by Preventing Spermatogenic Cell Apoptosis and Modulating Gene Expression in the Hypothalamic–Pituitary–Gonadal Axis

Hira Sayed,Qiongqiong Zhang,Yu Tang,Yanan Wang,Yongpeng Guo,Jianyun Zhang,Cheng Ji,Qiugang Ma,Lihong Zhao

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin found in many agricultural products and can cause reproductive disorders, mainly affecting spermatogenesis in male animals. Rutin (RUT) is a natural flavonoid compound recognized for its significant antioxidant, anti-inflammatory and estrogenic properties. The present study aimed to determine the protective role of RUT against ZEN-induced reproductive toxicity in male mice. Twenty-four adult Kunming male mice were divided into four groups: control, RUT (500 mg/kg RUT), ZEN (10 mg/kg ZEN), ZEN + RUT (500 mg/kg RUT + 10 mg/kg ZEN), with six replicates per treatment. The results indicated that RUT mitigated ZEN-induced disruption in spermatogenic cell arrangement, decreased spermatozoa count, and increased sperm mortality in the testes. RUT significantly restored ZEN-induced reduction in T, FSH, LH, and E2 serum levels. Moreover, RUT mitigated ZEN-induced apoptosis by increasing the mRNA expression level ofbcl-2, decreasing the mRNA expression level ofkiss1-r, and decreasing the protein expression level of caspase 8 in reproductive tissues. These findings indicate the protective role of RUT against ZEN-induced reproductive toxicity in male mice by regulating gonadotropin and testosterone secretions to maintain normal spermatogenesis via the HPG axis, which may provide a new application direction for RUT as a therapeutic agent to mitigate ZEN-induced reproductive toxicity.

研究领域: 毒理学 · 生殖生物学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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ENVIRONMENTAL POLLUTION · 2025 · IF 7.3

The exposure to nandrolone changed the expression of genes associated with sexual differentiation and disrupted the levels of hormones in the hypothalamic-pituitary-gonadal (HPG) axis, ultimately inducing male differentiation in zebrafish (Danio rerio)

Yufei Xie,Qiuyu Liu,Wenting Lin,Yuan Ren,Lingtian Xie

Various anabolic androgenic steroids (AAS) are frequently detected in aquatic environments, yet the potential ecotoxicological impacts of their increased load have not received adequate attention. This study investigates the effects of exposure to the androgen nandrolone on sex differentiation, gonadal development, and the expression of hormones, enzymes, and proteins related to the hypothalamic-pituitary-gonadal (HPG) axis in zebrafish. The results indicate that exposure to nandrolone at 60 days post-fertilization promotes the maturation of spermatogonia, inhibits the development of oocytes, and induces their apoptosis. Additionally, there were dose-dependent changes in male differentiation and hormone levels within the HPG axis: in the high-dose group (5 μg/L), males constituted 73 % of the population, and levels of E2 hormones in gonadal tissues decreased by 33 %, while T hormone levels increased by 55 %. Furthermore, the expression of genes essential for ovarian differentiation were downregulated, whereas the expression of testicular differentiation-related genes were upregulated. The molecular docking results show that the drug can form hydrogen bonds with key proteins, which have high affinity, and are more likely to cause conformational changes in the proteins, thereby altering their activity. KEGG analysis suggests that the MAPK signaling pathway is likely the target pathway through which nandrolone exposure induces reproductive toxicity.

CAS / MDL: 64-18-6 67-56-1
研究领域: 生态毒理学 · 分子生物学 · 内分泌学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Journal of Hazardous Materials Advances · 2025 · IF 7.7

Inulin improved endometrial ciliary damage caused by DEHP and nanoplastics co-exposure

Peigen Chen,Lina Chen,Xing Yang,Tingting Li,Cong Fang

The pervasive contamination by Di(2-ethylhexyl) phthalate (DEHP) and nanoplastics (NPs) poses a significant threat to reproductive health, yet the combined effects of these pollutants on endometrial receptivity remain poorly understood. Our study investigates the impact of chronic DEHP and NPs co-exposure on endometrial ciliary function in mice and explores the potential protective role of dietary inulin. Utilizing a multifaceted approach—including transcriptomic analysis, immunohistochemistry, scanning electron microscopy, and immunofluorescence—we reveal that DEHP and NPs synergistically impair endometrial cilia, crucial for embryo implantation. Remarkably, inulin supplementation restores ciliary structure and function, mitigating the detrimental effects of these pollutants. Our findings suggest that dietary interventions could offer a practical strategy to counteract the reproductive toxicity of environmental contaminants, providing new insights into maintaining reproductive health in polluted environments. This research underscores the urgency of addressing environmental pollutants and highlights the potential of inulin as a protective agent against reproductive toxicity.

CAS / MDL: 26446-38-8
研究领域: 生殖生物学 · 环境医学 · 营养学
✓ 已验证 产品关联 DOI 高影响因子
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COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY · 2019 · IF 2.697

Effect of nano zinc oxide on the acute and reproductive toxicity of cadmium and lead to the marine copepod Tigriopus japonicus

Xianliang Yi,Tongtong Chi,Bei Liu,Chenxi Liu,Guanqun Feng,Xinyu Dai,Keke Zhang,Hao Zhou

Given the absorbability of nZnO and its inevitable coexistence with trace metals such as Cd and Pb in coastal environment, nZnO can adsorb these pollutants thereby affecting their distribution in different media of marine ecosystem. The marine copepod Tigriopus japonicus was applied in the present study to investigate the combined effect of nZnO and Cd or Pb on mortality and reproduction in marine organisms. For acute exposure, presence of 1.0 mg/L nZnO increased the toxicity of both Cd and Pb, as their LC 50 decreased from 5.9 and 75.4 mg/L to 3.95 and 48.0 mg/L, respectively. For 21 d chronic exposure, the reproduction of the copepod was influenced by Cd and Pb at environmental relevant concentrations, and the interaction between nZnO and Cd or Pb appeared to be antagonistic. The waterborne Cd and Pb concentration was affected by nZnO for neither acute nor chronic exposure, indicating no adsorption of these two metals to nZnO at relative low concentration. The overall findings of this study suggested the binary exposure to nZnO/Cd or nZnO/Pb might have potential different toxic mechanisms between acute and chronic exposure.

CAS / MDL: 10108-64-2 10099-74-8
研究领域: 环境科学 · 毒理学 · 海洋生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ENVIRONMENTAL RESEARCH · 2025 · IF 7.7

Impact of the environmental endocrine disruptor 4-octylphenol on reproductive function in pubertal male mice

Zhenjun Zhao,Jingyi Chi,Zhang FangFang,Yinglin Song,Wenda Xv,Yan Li,Hui Shi

4-Octylphenol, a major environmental degradation product of alkylphenols (Aps) used in industry, is an endocrine-disrupting chemical with significant estrogenic activity. It is one of the most toxic Aps, poorly biodegradable in the environment, and can accumulate in organisms through the food chain, thereby affecting the male reproductive system. In this study, the effect of 4-octylphenol on male reproductive health was analyzed. Male pubertal mice were exposed to 4-octylphenol at doses of 0, 1, 10, and 100 mg/kg once daily for 28 days. Our findings indicated that pubertal exposure to 4-octylphenol has significant negative effects on the male reproductive system. Pubertal mice exposed to 4-octylphenol exhibited dose-dependent reproductive toxicity. In the medium- and high-dose groups, a significant reduction in testicular mass, structural damage to the seminiferous tubules, increased oxidative stress and apoptosis within the testicular tissue, and a decline in sperm quality were observed. Additionally, autophagy processes in the testicular tissue, germ cell proliferation, and meiotic processes are inhibited. Serum testosterone and estradiol levels decreased, whereas oxidative stress levels in the testes and spermatozoa increased. In contrast, the low-dose group showed only a reduction in body weight, a decrease in motile sperm count, and mild oxidative stress in the testes without significant pathological changes in Western blot experiments. These results indicate that 4-octylphenol exposure during puberty caused reproductive toxicity in male mice.

CAS / MDL: 140-66-9
研究领域: 毒理学 · 内分泌学 · 生殖健康
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMOSPHERE · 2024 · IF 8.1

Presence of microplastics enhanced the toxicity of silver nanoparticles on the collembolan Folsomia candida

Ying Ding,Jin-Ting Zheng,Ya-Ning Wang,Di Wu,Dong Zhu

There is growing interest in interactions of microplastics (MPs) with other pollutants. However, there is limited understanding of the combined effects of MPs and silver nanoparticles (AgNPs) on nontarget soil organisms. This work aimed to examine the effects of exposure to various AgNPs' concentrations alone (0, 0.1, 1, 10, 100, 1000 mg kg −1 , 50 nm) and in combination with polyvinyl chloride microplastics (PVC MPs, 80−250 μm) at 0.1% concentration for 28 days on reproduction, Ag accumulation, C/N ratio, and isotopic fractionation of the standard soil fauna collembolan Folsomia candida . Results showed that compared to the AgNPs exposure alone, the presence of MPs significantly reduced reproduction by 51.4% and markedly increased Ag content in collembolans by 87.7% at 1000 mg kg −1 AgNPs, which evidenced a synergistic effect. Co-exposure to MPs and AgNPs resulted in a noticeable reduction in the C/N ratio in F. candida body tissues by 9.90% and 5.27% at 1 and 10 mg kg −1 AgNPs, respectively, showing additive and synergistic effects. Additionally, this co-exposure altered stable isotope fractionation, with the highest increments of δ 15 N by 32.3% and inhibition of δ 13 C by 2.62%, demonstrating the turnover of nutrients shift in the collembolan tissues. Collectively, this study demonstrates that con-current exposure to environmentally relevant concentration of MPs and relatively high doses of AgNPs synergistically induces toxic effects on F. candida , leading to Ag accumulation and reproduction decline. These findings imply that MPs could alter collembolans' responses to AgNPs exposure, potentially enhancing the metal ions’ bioavailability in soil environments and posing ecotoxicological threats to soil-dwelling organisms.

CAS / MDL: 9002-86-2 7440-22-4
研究领域: 环境科学 · 生态毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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AQUATIC TOXICOLOGY · 2024 · IF 4.1

The detrimental effects and mechanisms of Orlistat in disrupting energy homeostasis and reproduction in Daphnia magna

Zhihua Ni,Xinling Tian,Wenbo Zhao,Wenkai Hu,Jinghua Lv,Xiaoli Sun,Yajie Zhang,Yiwen Zhang,Yuming Zhang,Baoku Li,Fengsong Liu

Orlistat (ORL) has been employed as an anti-obesity pharmaceutical for several decades. Given its low absorption rate, the majority of administered ORL is excreted into the environment with feces. It is crucial to collect scientific information regarding the possible ecological risks associated with ORL. Here, the effects of ORL on Daphnia magna were evaluated using a 21-day chronic test at concentrations of 1, 10, 100, and 1000 μg/L. We found the inhibition of feeding and swimming activities in the 100 and 1000 μg/L ORL exposed D. magna , respectively. Their digestive enzyme activities and metabolites were reduced even at 1 μg/L ORL exposure. It is noteworthy that exposure to 100 μg/L ORL induced a decrease in the reproductive capacity of D. magna , although no discernible genotoxicity was observed. To identify the toxicological mechanisms of ORL, a metabolic analysis was conducted on D. magna exposed to 1000 μg/L ORL. A comprehensive reduction in carbohydrates, lipids, and amino acids was observed, which resulted in a blockage of metabolic flux towards the TCA cycle, as evidenced by mitochondrial dysfunction. These findings substantiate the detrimental impact of ORL on D. magna and provide insights into the underlying molecular mechanisms from a metabolic perspective.

CAS / MDL: 7385-67-3 96829-58-2
研究领域: 环境科学 · 毒理学 · 生态学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY · 2023 · IF 6.8

Multigenerational effects and mutagenicity of three flame retardants on germ cells in Caenorhabditis elegans

Jiali Li,Linglong Dai,Yu Feng,Zhenxiao Cao,Yuting Ding,Hao Xu,An Xu,Hua Du

Flame retardants (FRs) have raised public concerns because of their environmental persistence and negative impacts on human health. Recent evidence has revealed that many FRs exhibit reproductive toxicities and transgenerational impacts, whereas the toxic effects of FRs on germ cells remain barely explored. Here we investigated the multigenerational effects of three flame retardants (TBBPA, TCEP and TCPP) on germ cell development in Caenorhabditis elegans , and examined the germ cell mutagenicity of these FRs by using whole genome sequencing. Parental exposure to three FRs markedly increased germ cell apoptosis, and impeded oogenesis in F1-F6 offspring. In addition, the double-increased mutation frequencies observed in progeny genomes uncover the mutagenic actions of FRs on germ cells. Analysis of mutation spectra revealed that these FRs predominantly induced point mutations at A:T base pairs, whereas both small and large indels were almost unaffected. These results revealed the long-term effects of FRs on development and genomic stability of germ cells, which may pose risks to environmental organisms and human reproductive health. Taken together, our findings suggest that germ cell mutagenicity should be carefully examined for the environmental risk assessment of FRs and other emerging pollutants.

CAS / MDL: 13674-84-5 115-96-8
研究领域: 环境科学 · 遗传学 · 毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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TOXICOLOGICAL AND ENVIRONMENTAL CHEMISTRY · 2019 · IF 0.971

Protective effects of vitamin E against bisphenol A-induced reproductive toxicity in male Kunming mice

Yu Wang,Jiayi Li,Rui Zhou,Lincai Yang,Peisheng He,Lixuan Chen,Liying Luo,Haowen Chen,Lian Wei

The protective effects of vitamin E (45, 150, and 500 mg/kg/d) against reproductive toxicity induced in male Kunming mice by intragastric administration of 120 mg/kg/d bisphenol A was investigated. After two weeks, relative organ weights, sperm counts, sperm abnormality rates and serum testosterone concentrations were determined. Epididymal sperm counts were significantly decreased, sperm abnormality was increased, and serum testosterone concentrations were dramatically reduced following bisphenol A exposure. Vitamin E treatment led to a marked increase in sperm numbers and a decrease in the proportion of malformed sperm in a dose-related manner; serum testosterone levels were also restored. This suggests that vitamin E could be used as prophylactic agent for preventing bisphenol A-induced reproductive toxicity.

CAS / MDL: 50-18-0
研究领域: 毒理学 · 生殖健康 · 营养学
✓ 已验证 产品关联 DOI 高影响因子
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2018 · IF 3.412

Determination of Five Sex Hormones in Urine Samples for Early Evaluation of Male Reproductive Toxicity Induced by Phthalate Esters in Rats

Liang-Liang Qian,Rui-Xian Li,Hai-Tao Gao,Chun-Min Wang,Lei Li,Qian Xu,Jian Li

In this work, male rats were exposed to multiple phthalate esters (MIXPs) in a long-term low-dose model for the early evaluation of reproductive toxicity. An ananlysis method with better sensitivity, accuracy and precision was established to determine the five sex hormones (androstenedione, testosterone, dehydroepiandrosterone, dihydrotestosterone, and estrone) in collected urine samples. The results showed that all the analytes in the MIXPs treated group changed in a time-dependent manner. Specifically, estrone significantly decreased from the 30th day and the other four changed from the 30th day and then significantly increased on the 60th day, while no obvious changes were found in the control group. Therefore, a possible way was provided for the early evaluation of male reproductive toxicity induced by Phthalate esters (PEs) . The reliability of judgment was improved by observing the changes of five target hormones simultaneously. Furthermore, good compliance was predicted for the practical application due to the noninvasive and convenient urine sample collection.

CAS / MDL: 53-16-7
研究领域: 毒理学 · 分析化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Toxics · 2023 ·Vol. 11 ·期 4 ·328 · IF 4.6

Difenoconazole Exposure Induces Retinoic Acid Signaling Dysregulation and Testicular Injury in Mice Testes

Xiangqin Zheng,Yuexin Wei,Jiadong Chen,Xia Wang,Dinggang Li,Chengjun Yu,Yifan Hong,Lianju Shen,Chunlan Long,Guanghui Wei,Shengde Wu

Difenoconazole (DFZ) is a broad-spectrum triazole fungicide that is widely utilized in agriculture. Although DFZ has been demonstrated to induce reproductive toxicity in aquatic species, its toxic effects on the mammalian reproductive system have yet to be fully elucidated. In vivo, male mice were administered 0, 20 or 40 mg/kg/d of DFZ via oral gavage for 35 days. Consequently, DFZ significantly decreased testicular organ coefficient, sperm count and testosterone levels, augmented sperm malformation rates, and elicited histopathological alterations in testes. TUNEL assay showed increased apoptosis in testis. Western blotting results suggested abnormally high expression of the sperm meiosis-associated proteins STRA8 and SCP3. The concentrations of retinoic acid (RA), retinaldehyde (RE), and retinol (ROL) were increased in the testicular tissues of DFZ-treated groups. The mRNA expression level of genes implicated in RA synthesis significantly increased while genes involved in RA catabolism significantly decreased. In vitro, DFZ reduced cell viability and increased RA, RE, and ROL levels in GC-2 cells. Transcriptome analysis revealed a significant enrichment of numerous terms associated with the RA pathway and apoptosis. The qPCR experiment verified the transcriptome results. In conclusion, our results indicate that DFZ exposure can disrupt RA signaling pathway homeostasis, and induce testicular injury in mice testes.Keywords:difenoconazole;reproductive toxicity;testis;retinoic acid signaling;GC-2 cell;apoptosis

研究领域: 毒理学 · 生殖生物学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF HAZARDOUS MATERIALS · 2025 · IF 11.3

Differentiated Distribution Between Albumen, Yolk and Eggshell of Parents and Metabolites Neonicotinoids and Their Reproductive Exposure Risk

Ke Gao,Ruyun Liu,Congyi Zheng,Shiyuan Wang,Kai Hua,Liping Lu,Zhiyong Guo

Differential distribution of neonicotinoids (NEOs) in albumen, yolk, and eggshell is a critical factor influencing their bio-accumulative behavior and the subsequent human health risks. However, there is currently no relevant research available. We collected 62 egg samples from 31 sampling sites across China and analyzed the concentrations and characteristics of 12 parents NEOs (p-NEOs) and 8   metabolites NEOs (m-NEOs) in albumen, yolk, and eggshell. NEOs were frequently detected in differentiated egg matrices, with the highest concentrations observed in Northeast China. The concentrations of m-NEOs were generally higher than those of p-NEOs. A positive correlation was found between the distribution of m-NEOs in albumen and their logKow (p<0.05). Dietary intake exposure posed a higher risk of NEOs to children and females. The toxicity equivalence (TEQ) of 5-hydroxy-imidacloprid and thiacloprid-amide, in interaction with androgen and estrogen receptors, was higher compared to other NEOs. Network toxicology and molecular docking indicated that AKT1 may serve as the core target for reproductive toxicity induced by dinotefuran, cycloxaprid, and nitenpyram exposure. This study provided valuable data on the occurrence, differential distribution, and reproductive exposure risk of NEOs in eggs for the first time. These findings are instrumental for future management policies concerning the environmental behavior and health effects of NEOs.

CAS / MDL: 7647-14-5 7757-82-6
研究领域: 环境科学 · 毒理学 · 食品科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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