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Airway particle exposure and developmental toxicity: From potential link to inflammation to within-laboratory reproducibility challenges 气道颗粒暴露和发育毒性:从与炎症的潜在联系到实验室内可重复性挑战。
IF 2.8 4区 医学 Q2 REPRODUCTIVE BIOLOGY Pub Date : 2025-12-18 DOI: 10.1016/j.reprotox.2025.109145
Karin Sørig Hougaard , Monika Hezareh Rothmann , Martin Roursgaard , Sandra Goericke-Pesch , Peter Møller , Luisa Campagnolo , Ulla Vogel
Research within nanotoxicology has revealed inhalation of particles can interfere with fetal development. Our research group has contributed knowledge on several aspects of developmental toxicity of manufactured nanomaterials. In some cases, the same batch of particles were examined in more than one mouse study. The present review evaluates whether our findings are within-laboratory reproducible and furthermore examines the potential relationships between induced maternal lung inflammation as a potential mediator of developmental toxicity, irrespectively of particle type. Our results ranged from fully reproducible (lack of effects on gestational and litter parameters, on germline mutations in females, irrespective of particle type, and on daily sperm production in F1 males of mothers exposed to carbon black; and depression of immune system function after maternal exposure to multiwalled carbon nanotubes) to not reproducible (transplacental genotoxicity and daily sperm production in the F2 generation of mothers exposed to carbon black and behavioral measures in general). Delineation of the relationship between maternal lung inflammation and developmental effects was somewhat hampered by differences time span from exposure termination to assessment of lung inflammation. At the observed levels, lung inflammation was however not associated with changes in gestational nor litter parameters, and did not seem to play a role in transplacental genotoxicity. In conclusion, this review reveals both consistency and variability in outcomes across studies. The results underscore the complexity of effects of nanoparticle exposure in developmental toxicology and reproducibility of results and warrants future research to focus on reproducibility and elucidate specific mechanisms underlying the observed toxicological effects.
纳米毒理学研究表明,吸入颗粒会干扰胎儿发育。我们的研究小组在人造纳米材料的发育毒性的几个方面做出了贡献。在某些情况下,同一批颗粒在多个小鼠研究中被检测。本综述评估了我们的研究结果是否在实验室内可重复,并进一步研究了诱导的母体肺部炎症作为发育毒性的潜在介质之间的潜在关系,而与颗粒类型无关。我们的结果包括完全可重复的(对妊娠和产仔参数没有影响),对雌性生殖系突变的影响,与颗粒类型无关,以及暴露于炭黑的母亲的F1雄性的每日精子产量;以及母体暴露于多壁碳纳米管后免疫系统功能的抑制)不可重复(暴露于炭黑的第2代母体的经胎盘遗传毒性和每日精子产量以及一般行为测量)。从暴露终止到肺部炎症评估的时间跨度差异,在一定程度上阻碍了母体肺部炎症与发育影响之间关系的描述。然而,在观察到的水平上,肺部炎症与妊娠和产仔参数的变化无关,似乎也没有在经胎盘遗传毒性中发挥作用。总之,这篇综述揭示了研究结果的一致性和可变性。这些结果强调了纳米颗粒效应在发育毒理学中的复杂性和结果的可重复性,并保证了未来的研究将重点放在可重复性和阐明观察到的毒理学效应的具体机制上。
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引用次数: 0
Placental toxicity of alternative plasticizers: Current knowledge and future directions 替代增塑剂的胎盘毒性:目前的知识和未来的方向。
IF 2.8 4区 医学 Q2 REPRODUCTIVE BIOLOGY Pub Date : 2025-12-17 DOI: 10.1016/j.reprotox.2025.109143
Maira Nadeem, Michelle Jojy, Margaret Meschia, Genoa R. Warner
Phthalates, a class of plasticizers, are known endocrine-disrupting chemicals that can negatively impact reproduction and development, including placental development and function. In response to growing concerns, various groups of chemicals, including but not limited to terephthalates, citrates, and cyclohexane dicarboxylic acids, have been developed as phthalate replacements. However, significant research gaps remain in understanding how these new chemicals affect humans. This review aims to synthesize existing research on how phthalate alternatives affect the placenta, a transient yet critical organ that supports fetal growth and development during pregnancy. Disruptions to placental structure and function can cause pregnancy complications and alter fetal programming. Herein, we review findings from biomonitoring, in vivo and in vitro experiments, as well as epidemiological studies to assess potential impacts. Although biomonitoring and house dust studies have identified the presence of alternative plasticizers, many identified chemical groups lack studies on their effects during pregnancy and on the placenta. Given the rising levels of these chemicals and their metabolites in urine and blood, further investigation into their mechanisms of toxicity is necessary. Notably, some alternatives may have the capability to alter pregnancy outcomes similar to traditional phthalates, such as by increasing the likelihood to develop conditions like gestational diabetes mellitus, although the majority of alternative plasticizers lack data. Understanding these impacts will inform public policy aimed at protecting maternal and fetal health, facilitate the development of safer consumer products, and prevent further emergence of regrettable replacements.
邻苯二甲酸酯是一类增塑剂,是一种已知的干扰内分泌的化学物质,会对生殖和发育产生负面影响,包括胎盘的发育和功能。为了应对日益增长的担忧,各种化学物质,包括但不限于对苯二甲酸盐、柠檬酸盐和环己烷二羧酸,已经被开发出来作为邻苯二甲酸盐的替代品。然而,在了解这些新化学物质如何影响人类方面,仍存在重大的研究空白。这篇综述的目的是综合现有的研究邻苯二甲酸盐替代品如何影响胎盘,一个短暂但重要的器官,支持胎儿在怀孕期间的生长和发育。胎盘结构和功能的破坏可引起妊娠并发症并改变胎儿程序。在此,我们回顾了生物监测、体内和体外实验以及流行病学研究的结果,以评估潜在的影响。虽然生物监测和室内粉尘研究已经确定了替代增塑剂的存在,但许多确定的化学类群缺乏对其在怀孕期间和对胎盘的影响的研究。鉴于这些化学物质及其代谢物在尿液和血液中的含量不断上升,有必要进一步研究它们的毒性机制。值得注意的是,一些替代品可能会像传统的邻苯二甲酸盐一样改变妊娠结果,比如增加患妊娠糖尿病等疾病的可能性,尽管大多数替代增塑剂缺乏相关数据。了解这些影响将为旨在保护孕产妇和胎儿健康的公共政策提供信息,促进开发更安全的消费品,并防止令人遗憾的替代品的进一步出现。
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引用次数: 0
Aqueous cigarette smoke extract reduces mitochondrial potential and increases nuclear degeneration in bovine oocytes matured in vitro 在体外成熟的牛卵母细胞中,含水香烟烟雾提取物降低线粒体电位并增加核变性。
IF 2.8 4区 医学 Q2 REPRODUCTIVE BIOLOGY Pub Date : 2025-12-17 DOI: 10.1016/j.reprotox.2025.109141
Ana Karen de Carvalho Albuquerque , Solano Dantas Martins , Leiz Maria Costa Véras , Alyne Rodrigues de Araújo Nobre , Vânia Marilande Ceccatto , Valdevane Rocha Araújo
This study investigated the cytotoxicity of different concentrations of aqueous extract of cigarette smoke (AECS) during in vitro maturation (IVM) of bovine oocytes, evaluating the potential synergy among its various compounds, including nicotine. The AECS was evaluated by liquid chromatography to identify nicotine amount and by atomic force microscopy (AFM) to analyze the morphology of particles. To IVM, bovine ovaries (n = 30) were collected in local slaughterhouse and submitted to slicing. Only oocytes that exhibited homogeneous cytoplasm, diameter higher than 110 µm, and surrounded by, at least, two layers of compact cumulus cells were selected. Cumulus-oocyte complex (COCs) were matured in groups under mineral oil in TCM-199 + alone (CTRL) or TCM-199 + supplemented with 1, 2.5 or 5 % of AECS, at 38,5°C in a humidified atmosphere containing 5 % CO2 in air for 24 h. After IVM period, oocytes were denuded and evaluated to chromatin configuration by Hoechst, and ROS and mitochondrial potential by H2DCFDA and JC-1, respectively. The data distribution was assessed using the Shapiro-Wilk test for homogeneity and ANOVA One-way with post hoc of Tukey considering P < 0.05. The results revelated high nicotine levels (158.40 µg/mL) in the AECS and nanoparticles with 14,66 ± 4,08 nm of diameter. Regardless of AECS concentration used, high chromatin degenerated rates of oocytes after IVM, and an increase of ROS levels and a reduction of mitochondrial (P < 0,05) was observed. Thus, it can be concluded that AECS exhibits significant cytotoxic properties towards bovine oocytes, particularly due to the presence of elevated concentrations of nicotine.
本研究研究了不同浓度的香烟烟雾水提取物(AECS)在牛卵母细胞体外成熟(IVM)过程中的细胞毒性,评估了其各种化合物(包括尼古丁)之间的潜在协同作用。采用液相色谱法测定烟碱含量,原子力显微镜(AFM)分析烟碱颗粒的形貌。在IVM中,在当地屠宰场收集牛卵巢(n=30)并进行切片。只选择细胞质均匀、直径大于110µm、被至少两层致密的积云细胞包围的卵母细胞。将积云卵母细胞复合体(COCs)分为两组,分别在中药-199+单独(CTRL)或中药-199+中添加1、2.5或5% AECS的矿物油作用下,在38.5℃、含5% CO2的潮湿环境中成熟24h。IVM期后,剥去卵母细胞,用Hoechst法测定染色质构型,用H2DCFDA法测定ROS和JC-1法测定线粒体电位。数据分布采用Shapiro-Wilk检验检验同质性和单因素方差分析,考虑P
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引用次数: 0
Total flavonoids of Epimedium ameliorate testicular damage via keap1–Nrf2/ARE signalling and multi-target regulation 淫羊藿总黄酮通过Keap1-Nrf2/ARE信号通路和多靶点调控改善睾丸损伤
IF 2.8 4区 医学 Q2 REPRODUCTIVE BIOLOGY Pub Date : 2025-12-16 DOI: 10.1016/j.reprotox.2025.109142
Hongchao Yuan , Wenhao Tian , Hao Hao , Sirui Kang , Fanfan Jia , Kai Chen , Xiaoying Zhang , Chen Chen
This study investigates the protective effects of total flavonoids of Epimedium (TFE) against obesity-induced testicular damage in mice. The potential pharmacological mechanisms were predicted using network pharmacology, molecular docking and molecular dynamics simulation. In vivo experiments were conducted in mice randomly assigned to five groups: a normal diet group, a high-fat diet (HFD) group, two TFE groups, and a positive control group. Biomarkers including dihydrotestosterone and testosterone were measured to evaluate testicular function, while lipid profiles were assessed. Oxidative stress was determined through glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) assays, and protein expression of heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), nuclear factor erythroid 2-related factor 2 (Nrf2), and Kelch-like ECH-associated protein 1 (Keap1) was analysed. Network pharmacology identified 29 flavonoids and 288 key targets. Molecular docking revealed that 22 active components exhibited strong binding activity, with PLCZ1–isoginkgetin/bilobetin showing the most stable conformation. TFE treatment significantly improved testicular function and mitigated obesity-induced male infertility. It enhanced sperm quality, reversed HFD-induced reductions in sperm count and motility, decreased malformation rates, normalized serum testosterone and dihydrotestosterone levels, ameliorated oxidative stress by enhancing antioxidant enzyme activity (GSH) and reducing lipid peroxidation (MDA), and improved lipid profiles by lowering triglycerides (TG) while increasing high-density lipoprotein cholesterol (HDL-C). Mechanistically, TFE upregulated Nrf2 pathway components (HO-1, NQO1) and modulated Keap1 expression. Collectively, these findings establish that the protective effects of TFE against obesity-induced testicular damage are mediated by the coordinated regulation of oxidative stress and key testicular targets.
本研究探讨淫羊藿总黄酮(TFE)对肥胖致小鼠睾丸损伤的保护作用。利用网络药理学、分子对接、分子动力学模拟等方法预测其潜在的药理机制。体内实验将小鼠随机分为5组:正常饮食组、高脂饮食组、2个TFE组和阳性对照组。测量包括双氢睾酮和睾酮在内的生物标志物来评估睾丸功能,同时评估脂质谱。通过谷胱甘肽(GSH)、超氧化物歧化酶(SOD)和丙二醛(MDA)检测氧化应激,分析血红素加氧酶-1 (HO-1)、NAD(P)H醌脱氢酶1 (NQO1)、核因子红系2相关因子2 (Nrf2)和kelch样ech相关蛋白1 (Keap1)的蛋白表达。网络药理学鉴定出29种黄酮类化合物和288个关键靶点。分子对接发现,22种活性成分均表现出较强的结合活性,其中plcz1 -异构体黄芪素/黄芪素的构象最稳定。TFE治疗可显著改善睾丸功能,减轻肥胖引起的男性不育症。它提高了精子质量,逆转了hfd引起的精子数量和活力的减少,降低了畸形率,使血清睾酮和双氢睾酮水平正常化,通过提高抗氧化酶活性(GSH)和减少脂质过氧化(MDA)来改善氧化应激,并通过降低甘油三酯(TG)和增加高密度脂蛋白胆固醇(HDL-C)来改善脂质谱。在机制上,TFE上调了Nrf2通路组分(HO-1、NQO1)并调节了Keap1的表达。总之,这些发现表明TFE对肥胖引起的睾丸损伤的保护作用是通过氧化应激和关键睾丸靶点的协调调节介导的。
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引用次数: 0
Persistent impact of in utero nanoparticle exposure on metabolic and endocrine outcomes in adult rats fed a high-fat diet 子宫内纳米颗粒暴露对高脂肪饮食成年大鼠代谢和内分泌结果的持续影响。
IF 2.8 4区 医学 Q2 REPRODUCTIVE BIOLOGY Pub Date : 2025-12-13 DOI: 10.1016/j.reprotox.2025.109140
Russell Hunter, Teresa Gluth, Kate Seman, Travis Goldsmith, Riley Nett, Victoria Nist, Allison Dunn, Eric Kelly, Elizabeth Bowdridge
Gestational nano titanium-dioxide (nano-TiO2) exposure causes reduced fetal size and multi-generational reproductive effects in females. The current study utilized a whole-body nano-TiO2 inhalation exposure model in pregnant Sprague-Dawley rats coupled with a high fat diet (HFD) fed to adult offspring to examine lasting effects of in-utero exposures on weight gain, metabolic function, and endocrine perturbations. Sexually dimorphic responses in weight gain were observed whereby exposed HFD males gained less weight than their air HFD counterparts (435 g ± 9.8 vs. 505 g ± 14.5; p < 0.05), but there was no weight difference between air and exposed HFD females. Males and females presented with exposure driven decreases in glucose tolerance, such that HFD exposed animals were significantly more glucose intolerant(-6985AUC±1763). Hypothalamic gene expression of the melanocortin receptor 3 was significantly increased in nano-TiO2 males (1453 %) and significantly decreased in nano-TiO2 females (29.07 %) compared to grain-based diet (GBD) controls. Hepatic mitochondrial activity was affected in sexually dependent manner, with females exhibiting changes in Complexes I, II, III, and V, and males only showing differences in Complex I activity. Finally, exposed males had smaller testicular mass (3.685 mg ± 0.0895 in GBD; 3.358 mg±0.0786 in HFD; (3.480 mg± 0.2023 in GBD, 3.380 mg± 0.0777) and reduced testosterone (7.75 µg/nl ± 1.965 in GBD; 3.62 µg/nl±2.084 in HFD; (9.943 µg/nl±1.97 in GBD, 4.28 µg/nl± 1.6845) compared to air males. Altogether, these data reflect how nanoparticulate driven differences in growth and development at birth can alter weight gain and metabolic function later in life in the face of a dietary challenge.
妊娠期纳米二氧化钛(纳米二氧化钛)暴露会导致胎儿尺寸减小和雌性多代生殖影响。本研究采用妊娠期Sprague-Dawley大鼠全身吸入纳米tio2暴露模型,并给成年后代喂食高脂肪饮食(HFD),以研究子宫内暴露对体重增加、代谢功能和内分泌紊乱的持久影响。在体重增加的两性二态反应中,暴露于HFD的男性体重增加少于空气中HFD的男性(435g±9.8比505g±14.5;p < 0.05),但暴露于空气中的HFD女性体重没有差异。雄性和雌性均表现出暴露导致的葡萄糖耐量下降,因此HFD暴露的动物明显更不耐受葡萄糖(-6985AUC±1763)。与以谷物为基础的饮食(GBD)对照组相比,纳米tio2雄性小鼠下丘脑黑素皮质素受体3基因表达显著增加(1453%),而纳米tio2雌性小鼠下丘脑黑素皮质素受体3基因表达显著降低(29.07%)。肝脏线粒体活性受性别影响,雌性表现出复合物I、II、III和V的变化,而雄性仅表现出复合物I活性的差异。最后,暴露于空气中的男性睾丸质量较小(GBD组为3.685mg±0.0895;HFD组为3.358mg±0.0786;GBD组为3.48 mg±0.2023,HFD组为3.380mg±0.0777),睾丸激素水平降低(GBD组为7.75µg/nl±1.965;HFD组为3.62µg/nl±2.084;GBD组为9.943µg/nl±1.97,HFD组为4.28µg/nl±1.6845)。总之,这些数据反映了纳米颗粒驱动的出生时生长发育差异如何在面对饮食挑战时改变生命后期的体重增加和代谢功能。
{"title":"Persistent impact of in utero nanoparticle exposure on metabolic and endocrine outcomes in adult rats fed a high-fat diet","authors":"Russell Hunter,&nbsp;Teresa Gluth,&nbsp;Kate Seman,&nbsp;Travis Goldsmith,&nbsp;Riley Nett,&nbsp;Victoria Nist,&nbsp;Allison Dunn,&nbsp;Eric Kelly,&nbsp;Elizabeth Bowdridge","doi":"10.1016/j.reprotox.2025.109140","DOIUrl":"10.1016/j.reprotox.2025.109140","url":null,"abstract":"<div><div>Gestational nano titanium-dioxide (nano-TiO<sub>2</sub>) exposure causes reduced fetal size and multi-generational reproductive effects in females. The current study utilized a whole-body nano-TiO<sub>2</sub> inhalation exposure model in pregnant Sprague-Dawley rats coupled with a high fat diet (HFD) fed to adult offspring to examine lasting effects of <em>in-utero</em> exposures on weight gain, metabolic function, and endocrine perturbations. Sexually dimorphic responses in weight gain were observed whereby exposed HFD males gained less weight than their air HFD counterparts (435 g ± 9.8 vs. 505 g ± 14.5; p &lt; 0.05), but there was no weight difference between air and exposed HFD females. Males and females presented with exposure driven decreases in glucose tolerance, such that HFD exposed animals were significantly more glucose intolerant(-6985AUC±1763). Hypothalamic gene expression of the melanocortin receptor 3 was significantly increased in nano-TiO<sub>2</sub> males (1453 %) and significantly decreased in nano-TiO<sub>2</sub> females (29.07 %) compared to grain-based diet (GBD) controls. Hepatic mitochondrial activity was affected in sexually dependent manner, with females exhibiting changes in Complexes I, II, III, and V, and males only showing differences in Complex I activity. Finally, exposed males had smaller testicular mass (3.685 mg ± 0.0895 in GBD; 3.358 mg±0.0786 in HFD; (3.480 mg± 0.2023 in GBD, 3.380 mg± 0.0777) and reduced testosterone (7.75 µg/nl ± 1.965 in GBD; 3.62 µg/nl±2.084 in HFD; (9.943 µg/nl±1.97 in GBD, 4.28 µg/nl± 1.6845) compared to air males. Altogether, these data reflect how nanoparticulate driven differences in growth and development at birth can alter weight gain and metabolic function later in life in the face of a dietary challenge.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"140 ","pages":"Article 109140"},"PeriodicalIF":2.8,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145763760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CORRIGENDUM, Long Term Exposure to Benzo[b]fluoranthene Does Not Induce Mutations in MutaMouse Male Germ Cells. Reprod Toxicol, 2025, 137:108985 http://doi.org/10.1016/j.reprotox.2025.108985 勘误:长期接触苯并[b]荧光蒽不会诱导突变小鼠雄性生殖细胞发生突变。中华生殖医学杂志,2015,37:108985 https://doi.org/10.1016/j.reprotox.2025.108985。
IF 2.8 4区 医学 Q2 REPRODUCTIVE BIOLOGY Pub Date : 2025-12-12 DOI: 10.1016/j.reprotox.2025.109138
Madison T. Stewart, Gu Zhou, Danielle P.M. LeBlanc, Annette E. Dodge, Matthew J. Meier, Andrew Williams, Alexandra S. Long, Paul A. White, Carole L. Yauk, Francesco Marchetti
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引用次数: 0
Effects of paternal 5G RFR exposure on health of male offspring mice 父本5G RFR暴露对雄性子代小鼠健康的影响。
IF 2.8 4区 医学 Q2 REPRODUCTIVE BIOLOGY Pub Date : 2025-12-12 DOI: 10.1016/j.reprotox.2025.109139
Zhang Zhaowen , Guo Ling , Zhou Guiqiang , Lin Jiajin , Qin Tongzhou , Li Jiangyi , Li Jing , Wang Fuli , Ding Guirong
With the widespread application of 5G communication technology, the potential health risks of radiofrequency radiation (RFR) have been paid much attention. Prior studies have demonstrated that the testes are highly sensitive to RFR, and notably, paternal epigenetic modifications can be transmitted to offspring, impacting their reproductive and neurobehavioral phenotypes. To investigate the intergenerational effects of paternal exposure to 5 G RFR on male offspring health, 7–8-week-old male C57BL/6 mice were randomly divided into Sham group and 4.9 GHz RFR group (16 mice per group). The mice in 4.9 GHz RFR group were exposed to 4.9 GHz RFR for 1 h/d over 42 consecutive days. Male offspring derived from exposed males and unexposed females were raised to adulthood. Anxiety and depression-like behaviors, learning and memory capabilities, sperm quality, and fertility in male offspring were assessed. Paternal testicular LRGUK gene (sperm motility-related) methylation, mRNA, and protein expression were detected. The results showed that paternal 5G RFR exposure induced anxiety-like behaviors and impaired sperm quality in F1 males, potentially associated with RFR-induced hypermethylation of paternal LRGUK gene and subsequent down regulation of its expression in offspring testes. No significant effects were observed on depression-like behaviors, cognitive performance, or fertility across F1-F2 generations. These findings indicated that paternal 5G RFR exposure induced intergenerational adverse effects on F1 males, potentially mediated by germ cell epigenetic modifications.
随着5G通信技术的广泛应用,射频辐射(RFR)的潜在健康风险日益受到人们的关注。先前的研究表明,睾丸对RFR高度敏感,值得注意的是,父亲的表观遗传修饰可以传递给后代,影响他们的生殖和神经行为表型。为了研究父亲接触5G RFR对雄性后代健康的代际影响,将7-8周龄雄性C57BL/6小鼠随机分为Sham组和4.9GHz RFR组(每组16只)。4.9GHz RFR组小鼠连续42天,每天1小时暴露于4.9GHz RFR。受辐射的雄性和未受辐射的雌性所生的雄性后代被抚养到成年。评估了男性后代的焦虑和抑郁样行为、学习和记忆能力、精子质量和生育能力。检测父亲睾丸LRGUK基因(精子活力相关)甲基化、mRNA和蛋白表达。结果表明,父本5G RFR暴露诱导F1雄性焦虑样行为和精子质量受损,可能与RFR诱导的父本LRGUK基因高甲基化及其随后在后代睾丸中表达下调有关。F1-F2代对抑郁样行为、认知表现或生育能力没有显著影响。这些发现表明,父本5G RFR暴露可能通过生殖细胞表观遗传修饰介导,对F1雄性产生代际不良影响。
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引用次数: 0
Perfluorodecanoic acid (PFDA) induces oxidative stress and autophagy dysregulation in HGrC1 cells 全氟癸酸(PFDA)诱导HGrC1细胞氧化应激和自噬失调。
IF 2.8 4区 医学 Q2 REPRODUCTIVE BIOLOGY Pub Date : 2025-12-09 DOI: 10.1016/j.reprotox.2025.109136
Rasha A. Barakat , Changyong Lee , Hannah B. Ball , Kendra L. Clark
Perfluorodecanoic acid (PFDA), a long-chain per- and polyfluoroalkyl substance (PFAS), is an emerging environmental toxicant, though little is known on its impact on female reproduction. This study investigates the cellular effects of PFDA on a human granulosa cell line, HGrC1, focusing on oxidative stress and autophagy pathways. HGrC1 cells were exposed to increasing concentrations (0.01 – 10 µM) of PFDA for 24, 48, 72, and 96 h. Notably, 10 µM PFDA for 48 h resulted in approximately 50 % reduction in cell viability, activation of cleaved caspase-3, reduced cell density, and altered morphology characterized by spindle-shaped elongation. qRT-PCR revealed significant downregulation of key antioxidant genes, particularly catalase. PFDA exposure markedly increased intracellular reactive oxygen species levels. Western blot analysis of the p62-Keap1-Nrf2 signaling pathway showed decreased KEAP1 protein levels and strong nuclear accumulation of NRF2 at 10 µM PFDA, supported by elevated expression of the downstream target HO-1. In parallel, PFDA disrupted autophagy regulation. Accumulation of p62, along with increased levels of LC3A/B, suggested impaired autophagic flux. Together, these findings demonstrate that PFDA compromises granulosa cell survival by inducing oxidative stress, altering antioxidant gene expression, and dysregulating autophagy. Given the central role of granulosa cells in follicular development and hormone synthesis, PFDA-induced toxicity may have significant implications for ovarian function and female fertility.
全氟癸酸(PFDA)是一种长链单氟烷基和多氟烷基物质(PFAS),是一种新兴的环境毒物,尽管人们对其对女性生殖的影响知之甚少。本研究探讨了PFDA对人颗粒细胞系HGrC1的细胞效应,重点关注氧化应激和自噬途径。HGrC1细胞暴露于浓度逐渐增加(0.01 - 10 µM)的PFDA中24、48、72和96 h。值得注意的是,10 µM PFDA作用48 h导致细胞活力降低约50% %,裂解caspase-3激活,细胞密度降低,并改变以纺锤形伸长为特征的形态。qRT-PCR显示关键抗氧化基因,尤其是过氧化氢酶显著下调。PFDA暴露显著增加细胞内活性氧水平。p62-Keap1-Nrf2信号通路的Western blot分析显示,在10 µM PFDA下,KEAP1蛋白水平下降,NRF2核积累强烈,下游靶点HO-1表达升高。与此同时,PFDA破坏了自噬调节。p62的积累以及LC3A/B水平的升高表明自噬通量受损。总之,这些发现表明PFDA通过诱导氧化应激、改变抗氧化基因表达和失调自噬来损害颗粒细胞的存活。考虑到颗粒细胞在卵泡发育和激素合成中的核心作用,pfda诱导的毒性可能对卵巢功能和女性生育能力有重要影响。
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引用次数: 0
Atrazine exposure during puberty causes long-lasting neurochemical alterations and sex-dependent sexual behavior deficits in rats 青春期接触阿特拉津会导致大鼠长期的神经化学改变和性别依赖性性行为缺陷。
IF 2.8 4区 医学 Q2 REPRODUCTIVE BIOLOGY Pub Date : 2025-12-09 DOI: 10.1016/j.reprotox.2025.109137
L.P. Pantaleon , J. Zaccarelli-Magalhães , M.E.S. Brandão , L.R. De-Paula , G.M. RibeirO , G.R. Abreu , J.W.P. Muñoz , J.C.B. Delorenzi , A.R. Fukushima , H.S. Spinosa , E.L. Ricci
Atrazine is one of the most used pesticides worldwide. It is detected in surface and groundwater, together with its active metabolite. In animals, atrazine’s toxic effects are neuroendocrine, behavioral, and developmental alterations, in both males and females. However, there are few studies on the effects of atrazine on an adult animal exposed during puberty. Thus, this study aims to evaluate the behavioral and neurochemical effects of atrazine exposure during puberty on adult male and female rats’ sexual behavior sphere. Wistar rats were exposed to different doses of atrazine (10, 30, or 100 mg/kg) by oral gavage from postnatal day 22–41 (period equivalent to human adolescence). The behavioral and neurochemical evaluation were conducted by analyzing body weight gain, as well as water and food intake during treatment; male sexual behavior through gait test, sexual motivation test, penile erection test, and sexual behavior test; female sexual behavior through sexual behavior test and estrous cycle evaluation; and dopaminergic and serotoninergic systems. Results showed 1) few alterations in body weight gain, as well as water and food intake during treatment in both males and females; 2) males had few alterations in sexual behavior (increase in the latency for first erection and lower number of post-ejaculatory intromissions); 3) females had no alterations of sexual behavior; and 4) both male and female had alterations in the brain dopaminergic and serotoninergic systems, with males being more responsive. Taking together these data suggests that atrazine causes long-lasting adverse effects that can affect a rat’s sexual performance.
阿特拉津是世界上使用最多的杀虫剂之一。在地表水和地下水中检测到它,连同它的活性代谢物。在动物中,阿特拉津的毒性作用表现为雄性和雌性的神经内分泌、行为和发育改变。然而,很少有关于阿特拉津对青春期暴露的成年动物的影响的研究。因此,本研究旨在评估青春期阿特拉津暴露对成年雌雄大鼠性行为领域的行为和神经化学影响。Wistar大鼠从出生后第22天至第41天(相当于人类青春期)通过灌胃方式暴露于不同剂量的阿特拉津(10、30或100mg/kg)。通过分析治疗期间的体重增加、水和食物摄入量进行行为和神经化学评估;男性性行为通过步态测试、性动机测试、阴茎勃起测试、性行为测试;通过性行为测试和发情周期评价女性性行为;多巴胺和血清素系统。结果表明:1)在治疗期间,男性和女性的体重增加以及水和食物摄入量几乎没有变化;2)男性在性行为方面几乎没有改变(初次勃起潜伏期增加,射精后插入次数减少);3)雌性无性行为改变;4)男性和女性的大脑多巴胺能和血清素系统都发生了变化,男性的反应更灵敏。综合这些数据表明,阿特拉津会造成长期的不良影响,影响老鼠的性行为。
{"title":"Atrazine exposure during puberty causes long-lasting neurochemical alterations and sex-dependent sexual behavior deficits in rats","authors":"L.P. Pantaleon ,&nbsp;J. Zaccarelli-Magalhães ,&nbsp;M.E.S. Brandão ,&nbsp;L.R. De-Paula ,&nbsp;G.M. RibeirO ,&nbsp;G.R. Abreu ,&nbsp;J.W.P. Muñoz ,&nbsp;J.C.B. Delorenzi ,&nbsp;A.R. Fukushima ,&nbsp;H.S. Spinosa ,&nbsp;E.L. Ricci","doi":"10.1016/j.reprotox.2025.109137","DOIUrl":"10.1016/j.reprotox.2025.109137","url":null,"abstract":"<div><div>Atrazine is one of the most used pesticides worldwide. It is detected in surface and groundwater, together with its active metabolite. In animals, atrazine’s toxic effects are neuroendocrine, behavioral, and developmental alterations, in both males and females. However, there are few studies on the effects of atrazine on an adult animal exposed during puberty. Thus, this study aims to evaluate the behavioral and neurochemical effects of atrazine exposure during puberty on adult male and female rats’ sexual behavior sphere. Wistar rats were exposed to different doses of atrazine (10, 30, or 100 mg/kg) by oral gavage from postnatal day 22–41 (period equivalent to human adolescence). The behavioral and neurochemical evaluation were conducted by analyzing body weight gain, as well as water and food intake during treatment; male sexual behavior through gait test, sexual motivation test, penile erection test, and sexual behavior test; female sexual behavior through sexual behavior test and estrous cycle evaluation; and dopaminergic and serotoninergic systems. Results showed 1) few alterations in body weight gain, as well as water and food intake during treatment in both males and females; 2) males had few alterations in sexual behavior (increase in the latency for first erection and lower number of post-ejaculatory intromissions); 3) females had no alterations of sexual behavior; and 4) both male and female had alterations in the brain dopaminergic and serotoninergic systems, with males being more responsive. Taking together these data suggests that atrazine causes long-lasting adverse effects that can affect a rat’s sexual performance.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"140 ","pages":"Article 109137"},"PeriodicalIF":2.8,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Corrigendum to “Irreversible male infertility from sleep restriction: A dual hit on testicular steroidogenesis and Keap1-Nrf2-mediated antioxidant defense” [Reprod. Toxicol. 138 (2025), 109083] “睡眠不足导致的不可逆转的男性不育:睾丸甾体激素生成和keap1 - nrf2介导的抗氧化防御的双重打击”的更正。中国生物医学工程学报,2003,19(5):393 - 393。
IF 2.8 4区 医学 Q2 REPRODUCTIVE BIOLOGY Pub Date : 2025-12-08 DOI: 10.1016/j.reprotox.2025.109135
Keke Chen , Fengyou Luo , Xiling Huang , Kaixing Huang , Xiaoyu Liu , Qiping Hu , Changlong Xu
{"title":"Corrigendum to “Irreversible male infertility from sleep restriction: A dual hit on testicular steroidogenesis and Keap1-Nrf2-mediated antioxidant defense” [Reprod. Toxicol. 138 (2025), 109083]","authors":"Keke Chen ,&nbsp;Fengyou Luo ,&nbsp;Xiling Huang ,&nbsp;Kaixing Huang ,&nbsp;Xiaoyu Liu ,&nbsp;Qiping Hu ,&nbsp;Changlong Xu","doi":"10.1016/j.reprotox.2025.109135","DOIUrl":"10.1016/j.reprotox.2025.109135","url":null,"abstract":"","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"140 ","pages":"Article 109135"},"PeriodicalIF":2.8,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145715759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Reproductive toxicology
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