Toxins
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2024
·Vol. 16
·期 3
·121
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IF 3.9
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
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生殖生物学
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分子生物学
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DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
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2025
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IF 7.3
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.
研究领域:
生态毒理学
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分子生物学
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内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
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2025
·
IF 11.3
Yufan Nie,Simin Yu,Luyao Zhang,Zikang Wang,Rui Liu,Yuping Liu,Wentao Zhu,Zhiqiang Zhou,Jinling Diao
Declines in reptile populations due to climate warming and environmental pollution have been documented. Although recent ecotoxicological studies of reptiles have increased, little is known about how these two stressors interact to affect reptile reproductive processes. This study investigated the single and combined effects of atrazine and warming on reproduction in female lizards (Eremias argus) following 10 weeks of exposure to environmentally relevant concentrations of atrazine (0–10 mg·kg–1) at two temperature treatments (control or warming). Reproductive traits, clutch characteristics, and endpoints related to endocrine disruption (HPG axis gene expression) and energy metabolism (enzyme activity, hepatic metabolomics) were assessed. Atrazine inhibits female reproduction by disrupting HPG axis-related gene expression and energy metabolism, resulting in delayed spawning time and reduced fecundity. In contrast, warming promoted female reproduction and partly alleviated the inhibitory effects of atrazine, which is related to the upregulation of HPG axis-related gene expression and an additional energy metabolism compensatory response. Additionally, atrazine and/or warming altered the direction and intensity of the trade-off between egg number and size and affected maternal nutritional investment in eggs. These findings highlight the complex interplay of environmental stressors on lizard reproduction and add to a better understanding of reptile reproductive strategies and ecological consequences under environmental stress.
研究领域:
生态学
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毒理学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2020
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IF 6.551
Dong Sun,Qi Chen,Bo Zhu,Hui Zhao,Shunshan Duan
Nonylphenol (NP) is a toxic xenobiotic compound, which is persistent in the aquatic environment and is extremely toxic to aquatic organisms. Although the exact molecular mechanisms of its toxic effect are well understood, the multigenerational reproduction and multigenerational - gene expression changes caused by NP still remain unclear. The following work investigated the effect of NP on four consecutive generations of zebrafish by examining their growth and several reproductive parameters, the degree of gonad damage, and the expression of related reproduction related genes. The results showed that high concentrations (20 and 200 μg·L −1 ) of NP could decrease growth and induce gonad damage in zebrafish. In addition, gnrh2 and gnrh3 genes were up-regulated, and fshβ and lhβ genes were downregulated in the hypothalamus in male zebrafish; while in female fish, the fshβ and lhβ were upregulated in P and F1 generations, and then down-regulated in the F2 generation. Meanwhile, the cyp19a1a gene was downregulated in the gonad of male fish, while the genes of fshr , lhr and esr showed a downward trend in females. Compared to P generation, F2 generation was more tolerant to higher NP concentrations (20 and 200 μg·L −1 ), as was also more sensitive to lower concentrations of NP (2 μg·L −1 ). Consequently, stress and damage caused by environmentally-relevant concentrations of aquatic pollutants in a vertebrate model were measured and predicted. Prevention and control measures can be actively and effectively proposed, which might be transversal to other exposed organisms, including humans. After several generations, typical transgenerational genetic phenomena might occur, which should be addressed by further studies.
研究领域:
环境科学
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毒理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
AQUATIC TOXICOLOGY
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2021
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IF 4.964
Naima Hamid,Muhammad Junaid,Rakia Manzoor,Jin-Jing Duan,Ming Lv,Nan Xu,De-Sheng Pei
Pharmaceuticals and personal care products (PPCPs) as emerging contaminants are ubiquitously present in the aquatic environment. Using in vivo and in silico techniques, this study aims to elucidate tissue distribution and endocrine disruption effects of chronic exposure (120 days) to PPCP mixture at environmentally relevant concentrations (ERCs) in adult zebrafish. Results from UHPLC-MS/MS analyses showed elevated distribution of PPCPs in zebrafish tissues in the order of liver > gonad > brain. Upregulation of steroid hormone receptors, both gonadotropin, and steroidogenic genes perturb the HPG axis pathway in females, while male fish exhibited significantly downregulated expressions of vtg, cyp17 , and 17βhsd genes with inhibited fecundity. The Spearman correlation indicated a significant positive relationship between PPCPs bioaccumulation and mRNA levels of HPG axis genes. In silico molecular docking (MD) revealed specific amino acid residues of PPCPs binding with zebrafish estrogen receptors. Furthermore, the strongest binding energies of sulfamethoxazole, carbamazepine, and triclosan were discovered in erα and erβ estrogen receptors, confirming PPCPs' xenoestrogenic behavior. To summarize, chronic exposure to ERCs resulted in a high accumulation of PPCPs in the liver and gonad tissues of adult zebrafish, as well as associated perturbed genetic responses. As a result, strict environmental regulations for the disposal of PPCPs should be ensured to protect ecological and public health.
研究领域:
环境科学
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毒理学
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水生生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ANALYST
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2024
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IF 3.6
Yinan Zhang,Guanghui Wang,Yongjian Shao,Pei Zheng,Chunyan Guo,Zhiqun Liu,Lilai Shen,Zhiquan Liu,Jiafeng Ding,Hangjun Zhang
To objectively quantify changes in steroid hormones in organisms caused by adverse environmental loads, we developed a simple and sensitive UPLC–MS/MS (ultra-performance liquid chromatography triple quadrupole mass spectrometry) method for the simultaneous determination of 18 steroid hormones on the HPG axis. This analytical method based on liquid extraction and a multimode electrospray and at-mospheric pressure chemical ionization (ESCi) source, which was optimized by mass spectrometry, liquid phase and pretreatment for the quantification of choles-terol [CH], aldosterone [A], cortisone [E], hydrocortisone [F], 21-deoxycortisol [21-DF], corticosterone [B], 11-deoxycortisol [11-DF], androstenedione [A2], estradiol [E2], estrone [E1], 2-methoxyestradiol [2-MeE2], 21-hydroxyprogesterone [21-OHP], 17-α hydroxyprogesterone [17α-OHP], testosterone [T], dehydroepiandrosterone [DHEA], progesterone [P4], dihydrotestosterone [DHT], and pregnenolone [P5]. The method exhibits linearity in the analyte-concentration range 0.03–1000 μg/mL range (r2 > 0.99), spiked recoveries for the concentration range tested are 76.22%–113.66%, and the relevant parameters of precision are 7.52%–1.14%. Compared to other method, this new method not only uses a small amount of serum (only 100 μL), but also permitted the analysis of the challenging steroids, cholesterol. Furthermore, the method was successfully applied to determination of steroids in Mus musculus, Carassius auratus, Rana catesbiana Shaw, and Rana nigromaculata serum samples from randomly selected individuals. This method may therefore be very useful tool as an efficient analysis method for assessing changes in steroid hormones.
研究领域:
分析化学
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内分泌学
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环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
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2024
·
IF 4.6
Shen Yifen,Zhang Le,Yang Tao,Li Xiaosong,Liu Chao,Li Hongmei,Hu Yanping,Shen Hao,Li Hua,Orlov Yuriy L.,Zhou Shasha,Shen Yihang
Puberty onset through hypothalamic-pituitary-gonad (HPG) axis as an important reproductive event in postnatal development is initiated from hypothalamic arcuate nucleus (ARC). The growing evidence indicates that translational control also plays an essential role in the final expression of gonadotropin genes. To investigate the role of protein translation and behavior of ribosomes in pubertal onset, the global profiles of transcriptome, single ribosome (monosome), polysome, and tandem mass tag proteome were comprehensively investigated in rat hypothalamic ARCs of different pubertal stages using RNA sequencing, polyribo sequencing, and mass spectrum. Transcriptome-wide enrichments of N6-methyladenosine and IGF2BP2 were investigated using meRIP and RIP sequencing. Monosome was robustly enriched on a large proportion of mRNA in early puberty rats (postnatal day (PND)-25) compared to late puberty (PND-35 and PND-45). Monosome-enriched mRNAs, including HPG axis-related genes, had a large number of upstream ORFs (uORF, < 100 nt) and displayed translational repression in early puberty. Furthermore, insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) could particularly interact with and facilitate monosome to bind with mRNA in early puberty. Finally, ectopic over-expression of IGF2BP2 in hypothalamic ARC via lateral ventricle injection in vivo could recruit monosome to aggregate on mRNA and delay puberty onset. We uncovered a novel regulatory mechanism of IGF2BP2 and monosome for translational control in puberty onset, which shed light on the neuroendocrine regulatory network involved in HPG axis activation.
研究领域:
神经内分泌学
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生殖生物学
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翻译调控
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）