Reproductive toxicology最新文献_第5页

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

Reproductive toxicology

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

Reproductive toxicology

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

Reproductive toxicology

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。

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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

Reproductive toxicology

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

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

Reproductive toxicology

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

Reproductive toxicology

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

Reproductive toxicology

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。

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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

Reproductive toxicology

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

引用次数: 0

Quantitative analysis and toxicological mechanisms of various male infertility inducers: A network meta-analysis and pharmacological approach 各种男性不育诱导剂的定量分析和毒理学机制：网络荟萃分析和药理学方法

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2025-12-05 DOI: 10.1016/j.reprotox.2025.109134

Muhammad Arif Asghar , Ao Zhang , Shixin Tang , Hang Han , Bing Wan , Jingwei Wu , Li Ping Wong , Xiao Zhang , Qinjian Zhao

Background

Male infertility is a global health concern, accounting for nearly half of all infertility cases. This study evaluates the toxicological effects of key infertility inducers in rodent models and explores underlying molecular mechanisms.

Methods

A systematic review and network meta-analysis (NMA) compared nine widely studied inducers: environmental toxicants (Bisphenol-A, Lead acetate, microplastics), pharmacological agents (Cyclophosphamide, Streptozotocin, Valproic acid, Tripterygium glycosides), and metabolic/physical stressors (High-Fat Diet, heat stress). Key endpoints included sperm count, motility, morphology, testis weight, and hormone levels. Network pharmacology and enrichment analyses identified molecular pathways, focusing on oxidative stress. Clinical relevance was assessed based on mechanistic alignment with human infertility.

Results

A total of 201 studies involving 3412 rodents were analyzed. NMA revealed significant differences in reproductive toxicity among inducers. Cyclophosphamide, STZ, and microplastics caused the most severe impairments, reducing sperm counts to 30.08 ± 19.1, 38.13 ± 8.2, and 18.97 ± 11.1 × 10⁶/mL, and motility to 31.73 ± 6.1 %, 30.74 ± 4.1 %, and 31.32 ± 10.2 %, respectively. Overall, sperm count, motility, and testosterone decreased by 1.46-, 1.21-, and 1.16-fold. Network pharmacology identified oxidative stress-related genes (NFE2L2, SOD1, HMOX1) as common targets, with oxidative stress emerging as shared mechanistic pathways. Trend analysis (2009–2024) revealed rising research on microplastics, HFD, and Lead acetate.

Conclusions

This first integrated toxicological and mechanistic analysis elucidates how diverse inducers impair male reproductive health. Oxidative stress contributes to toxicity, highlighting potential molecular targets for therapy. Findings support the translational relevance of rodent infertility models and guide risk assessment and mitigation strategies for stressors.

男性不育症是一个全球性的健康问题，占所有不育症病例的近一半。本研究在啮齿动物模型中评估了主要不育诱导剂的毒理学效应，并探讨了其潜在的分子机制。方法系统回顾和网络荟萃分析（NMA）比较了9种广泛研究的诱导因子：环境毒物（双酚a、醋酸铅、微塑料）、药物（环磷酰胺、链脲佐菌素、丙戊酸、雷公藤苷）和代谢/物理应激因子（高脂肪饮食、热应激）。关键终点包括精子数量、活力、形态、睾丸重量和激素水平。网络药理学和富集分析确定了分子途径，重点是氧化应激。根据与人类不孕症的机制一致性评估临床相关性。结果共分析201项研究3412只啮齿动物。NMA显示不同诱导剂的生殖毒性存在显著差异。环磷酰胺、STZ和塑料微粒引起的最严重的障碍,精子数量减少到30.08 ± 19.1,38.13 ± 8.2,和18.97 ±11.1  × 10⁶/ mL,和运动性 31.73±6.1  %,30.74 ±  % 4.1和31.32 ±10.2  %,分别。总的来说，精子数量、活力和睾丸激素分别下降了1.46倍、1.21倍和1.16倍。网络药理学发现氧化应激相关基因（NFE2L2, SOD1, HMOX1）是共同的靶点，氧化应激是共同的机制途径。趋势分析（2009-2024）显示，对微塑料、HFD和醋酸铅的研究正在增加。结论首次综合毒理学和机制分析阐明了不同诱导剂如何损害男性生殖健康。氧化应激有助于毒性，突出潜在的分子靶点治疗。研究结果支持啮齿动物不育模型的翻译相关性，并指导压力源的风险评估和缓解策略。

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引用次数: 0

Uterine artery transcriptomic signatures of e-cigarette aerosol exposure in pregnancy 妊娠期电子烟气溶胶暴露的子宫动脉转录组特征

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2025-12-04 DOI: 10.1016/j.reprotox.2025.109133

Alexander L. Carabulea , Vishal D. Naik , Joseph D. Janeski , Hong Jiang , Saravanan Venkatachalam , Jayanth Ramadoss

Electronic cigarette (e-cig) use among U.S. adults has shifted notably, with increased adoption among younger adults and middle-aged individuals transitioning from traditional cigarettes. We herein investigated the impact of gestational e-cig aerosol exposure on uterine artery (UA) transcriptome. Timed-pregnant Sprague-Dawley rats were randomly assigned to either the pair-fed Control or the E-cig group before initiation of vaping (4 s e-cig vapor every 2 min, two episodes of 1.5 h each; gestational day (GD) 5 until GD 20). Maternal weight and placental efficiency were not altered, whereas there was a significant deficit in fetal body weight and crown-rump length in the E-cig group on GD 21. Twenty three genes were significantly upregulated, while 40 genes were downregulated in the uterine artery of the E-cig group when compared with the Control group uterine artery. The top significantly downregulated genes in the uterine artery include genes involved in extracellular matrix and Wnt signaling regulation (Smoc2, Gpc3, Frzb, Sfrp2), immune and inflammatory response (C1qtTNF3, Tmem82, Clec21), muscle contraction (Actc1) and cell migration ( Gas2l3, Ret, Robo2). Top upregulated genes in the uterine artery (Vsig4, Agt, Cntn2, Kcnk5, Fhad1, Fgf13, Ctxn1, Prg4, and Pln) included genes involved in immune response and regulation (Vsig4, Kcnk5), and uterine artery vasodilation (Agt). Significant differences between the Control and E-cig groups were validated using Principal Component Analysis (PCA) and k-means clustering. These findings reveal how e-cig aerosol exposure during pregnancy may disrupt key biological processes in the uterine artery that delivers O₂ and nutrients to the fetoplacental compartment.

电子烟（e- cigg）在美国成年人中的使用发生了显著变化，越来越多的年轻人和中年人从传统香烟过渡到电子烟。我们在此研究了妊娠期电子烟气溶胶暴露对子宫动脉（UA）转录组的影响。定时怀孕的Sprague-Dawley大鼠在开始吸电子烟之前被随机分配到配对喂养的对照组或电子烟组（每2 分钟吸4 s电子烟，每次1.5 h，妊娠第5天至妊娠第20天）。母体体重和胎盘效率没有改变，而电子烟组在妊娠第21天胎儿体重和冠臀长明显下降。与对照组子宫动脉相比，电子烟组子宫动脉有23个基因显著上调，40个基因下调。子宫动脉中最显著下调的基因包括参与细胞外基质和Wnt信号调节的基因（Smoc2、Gpc3、Frzb、strp2）、免疫和炎症反应（C1qtTNF3、Tmem82、Clec21）、肌肉收缩（Actc1）和细胞迁移（Gas2l3、Ret、Robo2）。子宫动脉中上调最多的基因（Vsig4、Agt、Cntn2、Kcnk5、Fhad1、Fgf13、Ctxn1、Prg4和Pln）包括与免疫反应和调节有关的基因（Vsig4、Kcnk5）和子宫动脉血管舒张（Agt）。使用主成分分析（PCA）和k-means聚类验证对照组和电子烟组之间的显著差异。这些发现揭示了孕期接触电子烟气溶胶可能会破坏子宫动脉向胎儿胎盘室输送氧气和营养物质的关键生物过程。

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引用次数: 0