Animals
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2020
·Vol. 10
·期 3
·471
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IF 2.323
Aneela Perveen,Jiakun Shen,Niaz Ali Kaka,Chunmei Li
Simple SummaryThe experiment was designed to investigate the effect of gestational and lactational exposure to the T-2 toxin and its effects on the puberty of female mice offspring. T-2 toxin contaminates feed participates in the maternal diet. It directly interferes with the normal physiological function of offspring because the maternal diet is the most important during pregnancy and lactation. Female mice are more sensitive to the maternal diet during the lactation stage. Thus, their maturity stage is very complex and regulated by the hypothalamus, which controls Gonadotropin-releasing hormone (GnRH), and it also secretes reproductive hormones. Current findings report that T-2 toxins during late gestation and lactation period directly affect offspring, disturb the vaginal environment, delayed normal estrus cycle, and puberty age induces oxidative stress-caused ovarian damage. Based on findings, we think it is necessary to raise people’s attention to T-2 toxin-contaminated feed offered to animals. Current results reveal information about the health risks associated with a maternal diet, which affects the next generation.AbstractAmong foodborne toxicities, the T-2 toxin is the most toxic member of trichothecenes mycotoxins, which has been shown to impair the development and reproductive efficiency of animals. Pups are particularly more quickly prone to programming the effects of the maternal diet during the gestational and lactation periods. Few studies have reported the maternal toxic effect on the next generation. Dams were served the T-2 toxin at a dose of 0.005 and 0.05 mg/kg body weight/day and control group 0 mg/kg from gestation day 14 to lactation day 21. Female mice offspring were selected at the weaning age. Our observations indicate that age during the vaginal opening and di-estrus stage increased and the length of the estrus cycle, first di-estrus, and regular estrus cycling were delayed with prolonged di-estrus in the 0.05 mg/kg group compared to the 0.005 mg/kg and control group. Transcription level analysis showed that mice at a dose of 0.05 mg/kg exhibited a decrease in hypothalamic mRNA expression ofGnrhandGnrhr, Lhb,andFshbin the pituitary gland, with a significant decrease ofFshrandLhrin the ovaries. Present findings report that postnatal exposure to the T-2 toxin delayed puberty age in female mice and induced oxidative stress, ovarian damage, and reduced vaginal epithelium wall majorly in the 0.05 mg/kg group, and showed fewer effects in the 0.005 mg/kg group.Keywords:estrus cycle;mice;puberty;T-2 toxin
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
PubMed
高影响因子
CEREBRAL CORTEX
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2023
·
IF 3.7
Wan Changjian,Song Xueqing,Zhang Zhuyu,Hu Wenxiang,Chen Yanhua,Sun Wei,Liu Zhibin,Wang Songhua,Meng Wei
Physical exercise has been shown to have an impact on memory and hippocampal function across different age groups. Nevertheless, the influence and mechanisms underlying how voluntary exercise during puberty affects memory are still inadequately comprehended. This research aims to examine the impacts of self-initiated physical activity throughout adolescence on spatial memory. Developing mice were exposed to a 4-wk voluntary wheel running exercise protocol, commencing at the age of 30 d. After engaging in voluntary wheel running exercise during development, there was an enhancement in spatial memory. Moreover, hippocampal dentate gyrus and CA3 neurons rather than CA1 neurons exhibited an increase in the miniature excitatory postsynaptic currents and miniature inhibitory postsynaptic currents. In addition, there was an increase in the expression of NR2A/NR2B subunits of N-methyl-D-aspartate receptors and α1GABAA subunit of gamma-aminobutyric acid type A receptors, as well as dendritic spine density, specifically within dentate gyrus and CA3 regions rather than CA1 region. The findings suggest that voluntary exercise during development can enhance spatial memory in mice by increasing synapse numbers and improving synaptic transmission in hippocampal dentate gyrus and CA3 regions, but not in CA1 region. This study sheds light on the neural mechanisms underlying how early-life exercise improves cognitive function.
研究领域:
神经科学
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行为学
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DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
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2017
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IF 6.198
Xiaoqing Ye,Wuye Pan,Shilin Zhao,Yuehao Zhao,Yimin Zhu,Jing Liu,Weiping Liu
Although an acceleration of male pubertal development has been observed, precisely which endocrine-disrupting chemicals (EDCs) might contribute to the advancing onset of puberty in boys remains unclear. Here, pyrethroids, a class of widely used insecticides that have been considered as EDCs, are proposed as new environmental risk factors. In this study, 463 boys at the age of 9–16 years old were recruited in Hangzhou, Zhejiang, China. The common metabolites of pyrethroids, 3-phenoxybenzoic acid (3-PBA), and 4-fluoro-3-phenoxybenzoic acid (4-F-3-PBA), as well as gonadotropins, including luteinizing hormone (LH) and follicle-stimulating hormone (FSH), were analyzed in urine samples. Pubertal development was assessed based on Tanner stages and testicular volume (TV). A positive association between 3-PBA and gonadotropins was found (p < 0.001), in which a 10% increase in 3-PBA was associated with a 2.4% and 2.9% increase in LH and FSH, respectively. Higher urinary levels of 3-PBA in boys were associated with 275% and 280% increase in the risk of being genitalia stage 3 (G3) and G4, respectively (p < 0.05). There was a significant (132%) induction in odd of being TV 12–19 mL with increasing 3-PBA concentration compared to being in TV < 4 mL (p < 0.05). For the first time to our knowledge, this work reports on an association of increased pyrethroid exposure with elevated gonadotropins levels and earlier pubertal development in boys.
研究领域:
环境科学
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内分泌学
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公共卫生
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DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
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2021
·Vol. 29
·期 9
·13478-13490
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IF 4.223
Kang Lian,Chen Jiadong,Wang Junke,Zhao Tianxin,Wei Yuexin,Wu Yuhao,Han Lindong,Zheng Xiangqin,Shen Lianju,Long Chunlan,Wei Guanghui,Wu Shengde
The toxic effect of di(2-ethylhexyl) phthalate (DEHP) on prepubertal testes was examined in this study. We treated 3-week-old male mice with 4.8 mg/kg/day (milligram/kilogram/day) (no observed adverse effect level), 30 mg/kg/day (high exposure dose relative to humans), 100 mg/kg/day (level causing a reproductive system disorder), and 500 mg/kg/day (dose causing a multigenerational reproductive system disorder) of DEHP via gavage. Obvious abnormalities in the testicular organ coefficient, spermatogenic epithelium, and testosterone levels occurred in the 500 mg/kg DEHP group. Ribonucleic acid sequencing (RNA-seq) showed that differentially expressed genes (DEGs) in each group could enrich reproduction and reproductive process terms according to the gene ontology (GO) results, and coenrichment of metabolism pathway was observed by the Reactome pathway analysis. Through the analysis of common genes in the metabolism pathway, we discovered that DEHP exposure at 4.8 to 500 mg/kg or 100 mg/kg caused the same damages to the prepubertal testis. In general, we identified two key transcriptional biomarkers (fatty acid binding protein 3 (Fabp3) and carboxylesterase (Ces) 1d), which provided new insight into the gene regulatory mechanism associated with DEHP exposure and will contribute to the prediction and diagnosis of prepuberty testis injury caused by DEHP.
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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基因组学
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DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
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2017
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IF 5.099
Xiaoqing Ye,Wuye Pan,Yuehao Zhao,Shilin Zhao,Yimin Zhu,Weiping Liu,Jing Liu
Pyrethroids , a class of ubiquitous insecticides, have been considered as endocrine-disrupting chemicals (EDCs). Female animal studies suggested that early-life pyrethroids exposure might delay puberty onset. However, it remains unclear whether this association applies to human populations. A total of 305 girls at the ages of 9–15 years old were recruited in Hangzhou, China in this study. The concentration of the common metabolite of pyrethroids, 3-phenoxybenzoic acid (3-PBA), was analyzed in urine samples to reflect the exposure level of pyrethroids. The associations of 3-PBA with pubertal stages were evaluated using a multinomial logistic regression model. The geometric mean level of 3-PBA was 1.11 μg/L (1.42 μg/g for creatinine-adjusted concentration). There was a significant 45% reduction in odds of being in breast stage 3 (B3) per one-unit increase in the log-transformed 3-PBA levels [OR = 0.55 (95%CI: 0.31–0.98), p = 0.042]. A similar negative association was found between urinary 3-PBA levels with later onset by pubic hair stage 2 (P2) [OR = 0.56 (95%CI: 0.36–0.90), p = 0.015]. Similar negative association was also observed between urinary 3-PBA levels and pubertal onset indicated by menarche [OR = 0.51 (95%CI: 0.28–0.93), p = 0.029]. For the first time to our knowledge, this work reveals that pyrethroids exposure may increase the risk of delayed pubertal onset in girls.
研究领域:
环境科学
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公共卫生
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生殖健康
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
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2024
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IF 3.9
Chengping Kang,Qianqian Xiao,Xiaoxia Wang,Wanqian Guo,Haoran Zhang,Lilan Yuan,Zhe Zhao,Weidong Hao
Chlormequat chloride (CCC), a widely used plant growth regulator, is a choline analogue that has been shown to have endocrine-disrupting effects. Previous studies have shown that maternal exposure to CCC could induce hyperlipidemia and growth disruption in rat offspring. This study aims to further investigate the effects of peripubertal exposure to CCC on pubertal development and lipid homeostasis, as well as the underlying mechanisms. In vivo , male weanling rats were exposed to CCC (0, 20, 75 and 200 mg/kg bw/day) from post-natal day 21 to 60 via daily oral gavage. The results in rats showed that 75 mg/kg CCC treatment induced hepatic steatosis, predominantly microvesicular steatosis with a small amount of macrovesicular steatosis, in rat livers and 200 mg/kg CCC treatment induced liver damage including inflammatory infiltration, hepatic sinusoidal dilation and necrosis. In vitro , HepG2 cells were treated with CCC (0, 30, 60, 120, 240 and 480 μg/mL) for 24 h. And the results showed that CCC above 120 μg/mL induced an increase in triglyceride and neutral lipid levels of HepG2 cells. Mechanism exploration revealed that CCC treatment promoted the activation of mTOR/SREBP1 signalling pathway and inhibited activation of AMPK in both in vivo rat livers and in vitro HepG2 cells. Treatment with AMPK activator Acadesine (AICAR) could alleviate the lipid accumulation in HepG2 cells induced by CCC. Collectively, the present results indicate that CCC might induce hepatic steatosis by promoting mTOR/SREBP1 mediated lipogenesis via AMPK inhibition.
研究领域:
药理学
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毒理学
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内分泌学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Cells
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2025
·Vol. 14
·期 17
·1376
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IF 5.2
Zonghao Tang,Youkun Zheng
The maturation of testicular Leydig cells during the prepubertal stage is crucial for establishing male fertility. While diabetes is recognized as a significant detrimental factor affecting male testicular function, its impact specifically during the prepubertal period remains largely unknown. We hypothesized that prepubertal diabetes may impair testicular development by disrupting Leydig cell maturation. Using streptozotocin (STZ) administration, we established a prepubertal diabetic rat model and investigated the effects of diabetes on testicular development 2 and 4 weeks post-STZ treatment. Diabetes significantly hampered testicular development, manifesting as a decreased testicular weight, structural abnormalities, reduced testosterone levels, and increased inflammatory responses. As anticipated, prepubertal diabetes stagnated Leydig cell maturation and increased Leydig cell apoptosis. Mechanistic studies revealed that autophagy is essential for maintaining homeostasis and facilitating differentiation in immature Leydig cells but is significantly inhibited by hyperglycemia. Dysregulation of autophagy impaired the mitochondrial network, triggering inflammatory responses, suppressing steroidogenic capacity, and accumulating reactive oxygen species (ROS). Elevated ROS levels exacerbated the inflammatory response in the Leydig cells in an NLRP3-dependent manner. Inhibition of NLRP3 ameliorated the hyperglycemia-induced inflammation and decline in steroidogenic ability. Collectively, these findings demonstrate that hyperglycemia suppresses autophagy induction and enhances ROS accumulation in Leydig cells. This cascade promotes inflammation and inhibits steroidogenesis, thereby impeding testicular development in prepubertal diabetic rats.
研究领域:
内分泌学
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生殖生物学
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细胞生物学
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糖尿病研究
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DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2020
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IF 9.038
Junke Wang,Tianxin Zhao,Jiadong Chen,Lian Kang,Yuexin Wei,Yuhao Wu,Lindong Han,Lianju Shen,Chunlan Long,Shengde Wu,Guanghui Wei
Di(2-ethylhexyl) phthalate (DEHP) is a widely-used plasticizer and has long been recognized as an endocrine-disrupting chemical with male reproductive toxicities. DEHP exposure at the prepubertal stage may lead to extensive testicular injury. However, the underlying mechanisms remain to be elucidated. In the present study, we gavaged male C57BL/6 mice with different concentrations of DEHP (0, 250, and 500 mg/kg-bw·d) from postnatal day 22–35, and exposed TM3 Leydig cells with 0, 100, 200, 300, and 400 μM of MEHP (bioactive metabolite of DEHP) for 12–48 h. RNA sequencing was performed both in testicular tissue and TM3 cells. The results showed that DEHP disrupts testicular development and reduces serum testosterone levels in male prepubertal mice. Bioinformatic analysis and experimental verification have revealed that DEHP/MEHP induces cell cycle arrest in TM3 cells and increases apoptosis both in vivo and in vitro. Furthermore, the p53 signaling pathway was found to be activated upon DEHP/MEHP treatment. The inhibition of p53 by pifithrin-α significantly reduced MEHP-induced injuries in TM3 cells. Cumulatively, these findings revealed the involvement of the p53 signaling pathway in DEHP-induced prepubertal testicular injury by promoting cell apoptosis and inhibiting cell proliferation of Leydig cells.
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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生物信息学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
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2020
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IF 3.569
Jianxin Ye,Kangnan Zhang,Xindi Yuan,Haosen Ji,Miner Hu,Tongliang Huang,Ren-Shan Ge
Di -n- hexyl phthalate (DNHP) is commonly used as a plasticizer. However, whether DNHP influences Leydig cell development during puberty remains unexplored. In this study, DNHP (0, 10, 100, and 1000 mg/kg) was administered via gavage to 35-day-old male Sprague-Dawley rats for 21 days. Serum levels of testosterone, luteinizing hormone, follicle-stimulating hormone, Leydig cell number, the expression of Leydig and Sertoli cell genes and proteins were investigated. DNHP significantly increased serum testosterone levels at 10 mg/kg but lowered its level at 1000 mg/kg. DNHP significantly increased luteinizing hormone levels at 1000 mg/kg without affecting follicle-stimulating hormone levels. DNHP increased Leydig cell number at all doses but down-regulated the expression of Lhcgr , Hsd3b1 , Hsd17b3 , and Hsd11b1 in Leydig cell per se at 1000 mg/kg. DNHP elevated phosphorylation of ERK1/2 and GSK-3β at 10 mg/kg but decreased SIRT1 and PGC-1α levels at 1000 mg/kg. In conclusion, DNHP exposure causes Leydig cell hyperplasia possibly via stimulating phosphorylation of ERK1/2 and GSK-3β signaling pathways.
研究领域:
毒理学
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内分泌学
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生殖生物学
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DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
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2020
·
IF 6.793
Tian-Xin Zhao,Jun-Ke Wang,Lian-Ju Shen,Chun-Lan Long,Bin Liu,Yi Wei,Lin-Dong Han,Yue-Xin Wei,Sheng-De Wu,Guang-Hui Wei
Di-(2-ethylhexyl) phthalate (DEHP) is a common environmental endocrine disrupting chemical that may induce male reproductive disorders. Exposure to DEHP at a prepubertal stage could lead to prepubertal testicular injury, but the underlying mechanisms remain unclear. In this study, we exposed Sprague-Dawley rats to 0, 250, and 500 mg DEHP per kg body weight per day at the prepuberty stage from postnatal day 22 (PND 22) to PND 35 by oral gavage. Testicular injury and oxidative stress were evaluated, and the levels of 6-methyladenosine (m6A) modification and expression of modulator genes for RNA methylation were measured in testes . Furthermore, m6A modification of the important antioxidant transcription factor Nrf2 was analyzed using methylated RNA immunoprecipitation qPCR. Our results show that DEHP worsened testicular histology, decreased testosterone concentrations, downregulated expression of spermatogenesis inducers, enhanced oxidative stress, inhibited the Nrf2-mediated antioxidant pathway, and increased apoptosis in testes. Additionally, DEHP increased global levels of m6A RNA modification and altered the expression of two important RNA methylation modulator genes, FTO and YTHDC2 . Moreover, m6A modification of Nrf2 mRNA increased upon DEHP exposure. Overall, these findings link oxidative stress imbalance with epigenetic effects of DEHP toxicity and provide insight into the testicular toxicity of DEHP from the new perspective of m6A modification.
研究领域:
毒理学
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生殖生物学
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表观遗传学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
·
2024
·
IF 4.8
Junke Wang,Yuexin Wei,Yuhao Wu,Tianxin Zhao,Lian Kang,Lindong Han,Jiadong Chen,Chunlan Long,Guanghui Wei,Lianju Shen,Shengde Wu
As one of the most prevalent environmental endocrine disruptors, di-(2-ethylhexyl) phthalate (DEHP) is known for its significant developmental toxicity to the male reproductive system in humans and mice. Prepubertal exposure to DEHP has been shown to cause testicular damage, but the underlying mechanisms require further investigation. To investigate this effect, prepubertal mice were exposed to 250 or 500 mg/kg body weight (bw) of DEHP for 14 days, which resulted in impaired histological structure and increased apoptosis of the testes. RNA sequencing (RNA-seq) of testicular tissue suggested that DEHP led to injury in Leydig and Sertoli cells. To further elucidate these mechanisms, we conducted experiments using immature mouse Leydig (TM3) and Sertoli (TM4) cells, and exposed them to 200 μM mono-(2-ethylhexyl) phthalate (MEHP), the primary metabolite of DEHP, for 24 h. We found that MEHP exposure induced oxidative stress injury and promoted cell apoptosis, and that cotreatment with N-acetylcysteine partially reversed these injuries. Given the close association between oxidative stress and mitochondrial calcium levels, we demonstrated that MEHP exposure disrupted mitochondria and increased mitochondrial calcium levels. This effect facilitated the formation of mitochondria-associated endoplasmic reticulum membranes (MAMs), upregulated protein expression and enhanced the interactions of the IP3R3-Grp75-VDAC1 complex. Furthermore, inhibition of calcium transfer in the IP3R3-Grp75-VDAC1-MCU axis relieved MEHP-induced mitochondrial injury, oxidative stress and apoptosis in TM3 and TM4 cells. This study highlights the importance of MAM-mediated mitochondrial calcium overload and the subsequent apoptosis of Leydig and Sertoli cells as pivotal factors contributing to testicular injury induced by prepubertal exposure to DEHP.
研究领域:
环境科学
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毒理学
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生殖生物学
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细胞生物学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
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
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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）