MOLECULAR NUTRITION & FOOD RESEARCH
·
2023
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IF 5.2
Hui Cai,Dezhe Qin,Yundie Liu,Xinrui Guo,Yang Liu,Baohua Ma,Jinlian Hua,Sha Peng
Scope Systemic heat stress (or heatstroke; HS) induces germ cell death and spermatogenesis disorders in men and male mammals. Also, it affects the immune environment of the circulatory system promoting gut inflammation and intestinal permeability, leading to pathogenic infection. In this study, the crosstalk between the gut and testis (gut-testis axis) under HS is explored, by examining the effects of intestinal immune status on the health of the male reproductive system in mice. Methods and results A mouse model of systemic heat stress is established to investigate the effect of probiotics on testis health. The results reveal that pro-inflammatory factor receptor activation pathway and pathogen infection response pathway are significantly upregulated in HS testes, leading to necroptosis, while pro-inflammatory factor and endotoxin are detected locally in the intestine and then entered the blood. The study then uses probiotics to intervene in gut microbiota, which results in milder gut microbial changes, lower inflammatory responses in the HS gut, and less necroptosis in the HS testes. Conclusion Probiotics-based remodeling of gut microbiota (GM) reduces the proliferation of abnormal bacteria and decreases the spread of gut-derived inflammatory mediators into the blood circulation under long-term systemic heat stress, which relieves inflammation on germ cells.
研究领域:
生殖生物学
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免疫学
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微生物学
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分子生物学
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2024
·
IF 6.2
Danni Jiang,Yang Yang,Xiaojuan Han,Qianni Li,Pengfei Li,Yang Xu,Lan Chao
Past studies have observed that BHPF induces multi-organ toxicity, however, whether it induces damage to male reproductive system and the specific mechanism remains unclear. In the present study, male mice were given 0, 2, 10 or 50 mg/kg/day of BHPF by gavage for 35 days to observe its effect on reproductive organ and sperm quality. The results indicated that BHPF decreased sperm count and sperm motility in a dose-dependent manner. Besides, our results demonstrated that BHPF triggered the proliferation inhibition and cell death of germ cells in vivo and in vitro. Also, BHPF reduced the expression of function markers for germ cells, Sertoli cells, and Leydig cells, indicating its damage to function of testis cells. Simultaneously, testicular microenvironment was found to be altered by BHPF, as presented with declined testosterone level and decreased expression of local microenvironment regulators. Overall, our findings indicated the detrimental effects of BHPF on male reproductive function in mice, suggesting testicular function and local microenvironment disturbance as mechanism underlying testicular damage.
研究领域:
毒理学
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生殖生物学
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内分泌学
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DOI
高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2020
·Vol. 27
·期 14
·17290-17302
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IF 3.056
Ma Lin,Yu Haiyang,Wang Xu,Li Dan,Zhang Yumin,Pei Xiucong,Duan Zhiwen,Ma Mingyue
The effect of prenatal bisphenol A (BPA) exposure is increasingly concerned. We investigated the effect of maternal BPA exposure during pregnancy on male offspring and its potential mechanism. Thirty pregnant Sprague Dawley (SD) rats were randomly divided into exposed and control groups. At PND56, the number of sperm, luteinizing hormone, and testosterone in the BPA-exposed group decreased, and testicular tissue structure was damaged in offsprings. At GD20, the miRNA profile in the testis of male offspring was examined and the expression levels of 28 deregulated miRNAs were validated by qRT-PCR. We found that miR-361-5p , miR-203a-3p , and miR-19b-2-5p had significantly different expression levels in the testis. These results suggest that maternal exposure to BPA can lead to differential changes in progeny miRNAs, which will provide direction for future in-depth mechanisms of reproductive injury.
研究领域:
生殖生物学
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毒理学
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分子生物学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
REPRODUCTIVE TOXICOLOGY
·
2025
·
IF 2.8
Huage Liu
Thirdhand smoke (THS), a residual cigarette smoke still remaining in indoor environment long after active smoking has ceased, has aroused more and more people’s attention on health. However, the impact of THS exposure on the male reproductive system, particularly in in-vivo study, remain unclear. Thus, this study aims to investigate the adverse effects of 1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal (NNA), a special component in THS, on testis. Herein, adult ICR mice were orally administered diluted dimethylsulfoxide (control), 0.075 μg/kg and 0.15 μg/kg NNA for 10 weeks. The findings revealed that NNA exposure, especially in 0.15 μg/kg dosage, significantly reduced the epithelium height and tubular area within the testis. Transcriptomic analysis indicated that NNA exposure interfered with the expression of genes associated with oxygen transport and oxygen binding processes, such as Hbb-bs , the downregulation of which also led to oxidative damage. Additionally, NNA exposure induced oxidative damage in testis by decreased levels of SOD and GSH enzymes, along with an increase in MDA level. In summary, our results demonstrate that NNA exposure causes impaired testicular structure and oxidative damage, indicating its testicular toxicity. This finding not only implies the detrimental effect of NNA on male reproduction, but also provides a fundamental basis for further research on the impact of THS exposure on male reproductive health.
研究领域:
毒理学
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生殖健康
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环境健康
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2024
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IF 3.9
Penghui Nie,Siyue Wen,Mengqi Wang,Hengyi Xu
The decline in male sperm quality caused by multiple factors has become a widespread concern. Alcohol excessive consumption is one of the factors that induce testicular dysfunction. Testicular dysfunction caused by alcohol abuse is related to oxidative stress and inflammation. Probiotics can ameliorate alcohol-induced testicular dysfunction. However, the specific mechanism is not explicit. This study aimed to elucidate the underlying mechanism by which Lactiplantibacillus plantarum P101 ameliorates the alcohol-induced testicular dysfunction. The model of alcohol-induced testicular dysfunction in C57B/6 male mice was established according to the National Institute on Alcohol Abuse and Alcoholism, and Lactiplantibacillus plantarum P101 supplementation was orally administered to mice during the experiment. The results showed that Lactiplantibacillus plantarum P101 promoted androgen production, reduced testis inflammation, and improved testis antioxidant capacity , thereby improving sperm quality and sperm motility and ultimately ameliorating alcohol-induced testicular disorder. Three key metabolite pathways and six key metabolites were identified by metabolome analysis.
研究领域:
微生物学
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生殖生物学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL RESEARCH
·
2025
·
IF 7.7
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.
研究领域:
毒理学
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内分泌学
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生殖健康
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
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2020
·Vol. 27
·期 20
·25278-25286
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IF 3.056
Wang Jicang,Zhu Huali,Wang Ke,Yang Zijun,Liu Zongping
Cadmium (Cd), a highly toxic heavy metal, adversely affects human and animal health. Quercetin (Que) is a kind of flavonoid that can protect many tissues from the toxic effect of heavy metals. Although many studies have explored the adverse effects of cadmium on rats and other animals, the mechanism of Cd-induced testicular autophagy and the antagonistic effect of Que on cadmium remain unclear. In this study, Sprague–Dawley rats were treated with Cd, Que or Cd, and Que supplements to explore the mechanisms of Que-alleviated testis injury caused by Cd exposure. The rat body weight and relative testicular weight were measured. Morphological changes in testes and indices of oxidative stress were also examined. The expression levels of autophagy-related genes were detected as well. Results showed that Cd decreased the rat body weight and relative testicular weight and induced pathological changes in testes. Conversely, Que alleviated these changes. We also found that Cd increased the malondialdehyde content and decreased the contents of total superoxide dismutase, glutathione peroxidase, catalase, and glutathione. Moreover, the protein expression levels of P62 and LC3-II increased under Cd exposure conditions. Conversely, Que obviously alleviated these toxic activities induced by Cd. Overall, this study showed that Cd accumulated in rat testes, leading to oxidative stress and autophagy. Que can reduce cadmium toxicity by reducing oxidative stress and inhibiting autophagy. The specific mechanism of Que antagonizing Cd toxicity can provide new insights into countering cadmium toxicity.
研究领域:
毒理学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
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2022
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IF 9.988
Wenjing Pu,Xuesheng Chu,Huiling Guo,Gang Huang,Ting Cui,Bingyan Huang,Xueyan Dai,Caiying Zhang
Cadmium (Cd) and excess molybdenum (Mo) have multiple organ toxicity, and testis is one of their important target organs, but the reproductive toxicity of Mo and Cd combined treatment is still unclear. To explore the effects of Mo and Cd co-exposure on DNA damage and autophagy from the insight of ATM/AMPK/mTOR axis in duck testes, we randomly assigned 40 healthy 8-day-old ducks to control, Mo (100 mg/kg Mo), Cd (4 mg/kg Cd), and Mo + Cd groups for 16 weeks. Results found that Mo and/or Cd exposure caused trace elements imbalance, oxidative stress with a decrease in the activities of GSH-Px, CAT , T-SOD and GSH content, an increase in the concentrations of H 2 O 2 and MDA and pathological damage. Additionally, Mo and/or Cd markedly raised DNA damage-related factors expression levels and 8-OHdG content, caused G1/S arrest followed by decreasing CDK2 and Cyclin E protein levels and increasing CDK1 and Cyclin B protein levels, and activated ATM/AMPK/mTOR axis by enhancing p-ATM/ATM, p-AMPK/AMPK and reducing p-mTOR/mTOR protein levels, eventually triggered autophagy by elevating LC3A, LC3B, Atg5, Beclin-1 mRNA levels and LC3II/LC3I, Beclin-1 protein levels and reducing P62, Dynein, mTOR mRNA levels and P62 protein level. Moreover, these changes were most apparent in the combined group. Altogether, the results reveal that autophagy caused by Mo and/or Cd may be associated with activating the DNA damage-mediated ATM/AMPK/mTOR axis in duck testes, and Mo and Cd co-exposure exacerbates these changes.
研究领域:
毒理学
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生殖生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Toxics
·
2023
·Vol. 11
·期 4
·328
·
IF 4.6
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
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生殖生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2025
·
IF 4.2
Yulong Li,Shu Wang,Rui Feng
Cadmium (Cd) is a non-essential heavy metal that is highly toxic to testicle. Selenium (Se) is known to possess antagonistic effects against Cd toxicity, yet the precise mechanisms through which Se counteracts Cd-induced testicular damage in chickens through Nuclear factor erythroid 2-related factor 2/Heme oxygenase-1 (Nrf2/HO-1) signaling pathway, oxidative stress (OS), apoptosis, and inflammation remained unclear. In the present study, the experimental model of chicken testis was established by incorporating CdCl 2 and Na 2 SeO 3 into the dietary intake. After 60 days, chickens from each group were euthanized, and testicular and serum samples were subsequently collected. Ultrastructural assessment revealed that Se supplementation significantly mitigated the testicular damage induced by Cd. Se effectively suppressed the Cd-induced elevation in ROS, MDA, and H 2 O 2 levels, while also preventing the downregulation of CAT, GSH, and T-AOC levels. Furthermore, Se administration ameliorated the reduction in the expression levels of Nrf2, HO-1, and Bcl-2 induced by Cd, and counteracted the overexpression of Caspase-3, Bax, Cyt-c, and Caspase-9, TNF-α, IL-2, IL-6, and IL-1β. Meanwhile, immunofluorescence data demonstrated that Se attenuated the Cd-induced decrease in Nrf2 and HO-1 expression and the upregulation of IL-6 expression. In conclusion, this study elucidated that Se might mitigate Cd-induced oxidative stress in chicken testicles through the stimulation of the Nrf2/HO-1 signaling pathway, thereby inhibiting apoptosis and inflammation, and was beneficial in reducing Cd-induced testicular injury.
研究领域:
毒理学
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生殖生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2024
·
IF 3.8
Jiamei Zhu,Xueyan Dai,Yan Wang,Ting Cui,Bingyan Huang,Dianyun Wang,Wenjing Pu,Caiying Zhang
Cadmium ( Cd ) and high molybdenum ( Mo ) are injurious to the body. Previous research has substantiated that Cd and Mo exposure caused testicular injury of ducks, but concrete mechanism is not fully clarified. To further survey the toxicity of co-exposure to Cd and Mo in testis, 40 healthy 8-day-old Shaoxing ducks ( Anas platyrhyncha ) were stochasticly distributed to four groups and raised with basic diet embracing Cd (4 mg/kg Cd) or Mo (100 mg/kg Mo) or both. At the 16th week, testis tissues were gathered. The characteristic ultrastructural changes related to apoptosis and ferroptosis were observed in Mo or Cd or both groups. Besides, Mo or Cd or both repressed nuclear factor erythroid 2-related factor 2( Nrf2 ) pathway via decreasing Nrf2, Heme oxygenase-1 ( HO-1 ), NAD(P)H quinone oxidoreductase 1 ( NQO1 ), Glutamate-cysteine ligase catalytic subunit ( GCLC ) and Glutamate-cysteine ligase modifier subunit ( GCLM ) mRNA expression of and Nrf2 protein expression, then stimulated apoptosis by elevating Bcl-2 antagonist/killer-1 ( Bak-1 ), Bcl-2-associated X-protein ( Bax ), Cytochrome complex ( Cyt-C ), caspase-3 mRNA expression, cleaved-caspase-3 protein expression and apoptosis rate, as well as reducing B-cell lymphoma-2 ( Bcl-2 ) mRNA expression and ratio of Bcl-2 to Bax, and triggered ferroptosis by upregulating Acyl-CoA Synthetase Long Chain Family Member 4 ( ACSL4 ), transferrin receptor ( TFR1 ) and Prostaglandin-Endoperoxide Synthase 2 ( PTGS2 ) expression levels, and downregulating ferritin heavy chain 1 ( FTH1 ), ferritin light chain 1 ( FTL1 ), ferroportin 1 ( FPN1 ), solute carrier family 7 member 11 ( SCL7A11 ) and glutathione peroxidase 4 ( GPX4 ) expression levels. The most obvious changes of these indexes were observed in co-treated group. Altogether, the results announced that Mo or Cd or both evoked apoptosis and ferroptosis by inhibiting Nrf2 pathway in the testis of ducks, and co-exposure to Mo and Cd exacerbated these variations.
研究领域:
毒理学
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生殖生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
STAR Protocols
·
2022
·
IF 0
Yuzhu Cao,Lan Meng,Yu Cheng,Muhammad Azhar,Xue Jiang,Xuemei Xing,Jianqiang Bao
Summary Germline development is challenging to study due to the diversity of cell types in mammalian testis. Here, we present an optimized protocol, namely centrifugal elutriation, that allows the simultaneous isolation of mouse germ cells at different stages with high purity within ∼2 h. This approach exploits the JE-5.0 centrifugal elutriation system that fractionates cells based on differential sedimentation gravity. We herein provide the optimized parameters and procedures for isolation of elongating spermatids, round spermatids, and pachytene spermatocytes from adult mouse testes. For complete details on the use and execution of this protocol, please refer to Bao et al. (2018) .
研究领域:
生殖生物学
·
细胞生物学
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发育生物学
✓ 已验证
DOI
PubMed
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