Reproductive toxicology最新文献_第6页

Alogliptin attenuates testicular damage induced by monosodium glutamate in both juvenile and adult male rats by activating autophagy: ROS dependent AMPK/mTOR 阿格列汀通过激活自噬：ROS依赖性AMPK/mTOR，减轻幼年和成年雄性大鼠味精诱导的睾丸损伤。

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-12-24 DOI: 10.1016/j.reprotox.2024.108826

Manal Mohammad Morsy , Heba A. Hassan , Reham M. Morsi , Ola Elsayed Nafea , Azza I. Farag , Rania Saad Ramadan

Monosodium glutamate (MSG) is one of the most commonly used food additives, known for its adverse health effects. Alogliptin (ALO) is a highly selective dipeptidyl peptidase-4 inhibitor, but its role in male reproductive function remains debated. The study was designed to evaluate and compare the potential of ALO in mitigating MSG-induced testicular toxicity in juvenile and adult male rats. Juvenile and adult male rats were treated with either MSG or pretreated with ALO before MSG administration. The rats then received ALO and MSG concurrently for 28 days. Testicular tissues were isolated and subjected to histo-biochemical and molecular assessments. Our results demonstrated that ALO reversed MSG-induced testicular injury, as evidenced by the restoration of reproductive hormone balance (increased serum luteinizing hormone and testosterone concentrations), suppression of oxidative stress injury (decreased testicular malondialdehyde, increased superoxide dismutase activity, and minimal 8-hydroxy-2′-deoxyguanosine immunoreactivity), inflammation (reduced testicular tumor necrosis factor-alpha levels), and fibrosis (decreased testicular collagen fiber deposition). Additionally, ALO impeded apoptosis and activated autophagy by decreasing caspase-3 activity, stimulating the AMPK/mTOR pathway, downregulating Bax and SQSTM-1/p62 expression, upregulating Bcl2 and Beclin 1, promoting testicular proliferation (increased number of proliferating cell nuclear antigen-positive cells in the testis), restoring glycogen content in the testis (mild to moderate periodic acid-Schiff reaction), and preserving testicular architecture. MSG induced more severe adverse testicular effects in juvenile rats, while ALO pretreatment was more protective in adult rats. ALO's anti-inflammatory, antioxidant, antiapoptotic, pro-autophagic, antifibrotic, and proliferative actions in the testis suggest its promising potential for combating male reproductive dysfunction.

味精（MSG）是最常用的食品添加剂之一，因其对健康的不良影响而闻名。阿格列汀（ALO）是一种高选择性二肽基肽酶-4抑制剂，但其在男性生殖功能中的作用仍存在争议。本研究旨在评估和比较ALO在减轻味精诱导的幼年和成年雄性大鼠睾丸毒性方面的潜力。幼年和成年雄性大鼠在给药前分别给予味精或ALO预处理。随后，大鼠同时接受ALO和味精同时治疗28天。分离睾丸组织，进行组织生化和分子评价。我们的研究结果表明，ALO逆转了msg诱导的睾丸损伤，证明了恢复生殖激素平衡（增加血清黄体生成素和睾酮浓度），抑制氧化应激损伤（降低睾丸丙二醛，增加超氧化物歧化酶活性，降低8-羟基-2'-脱氧鸟苷免疫反应性），炎症（降低睾丸肿瘤坏死因子- α水平）。纤维化（睾丸胶原纤维沉积减少）。此外，ALO通过降低caspase-3活性，刺激AMPK/mTOR通路，下调Bax和SQSTM-1/p62表达，上调Bcl2和Beclin 1，促进睾丸增殖（睾丸中增殖细胞核抗原阳性细胞数量增加），恢复睾丸中糖原含量（轻度至中度周期性酸-席夫反应），并保持睾丸结构，从而抑制细胞凋亡和激活自噬。味精对幼年大鼠的睾丸不良反应更为严重，而ALO预处理对成年大鼠的保护作用更强。它在睾丸中的抗炎、抗氧化、抗凋亡、促自噬、抗纤维化和增殖作用表明它在对抗男性生殖功能障碍方面有很大的潜力。

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引用次数: 0

Role of the endocannabinoid system in gonadal development: Implications for endocrine disruption and reproductive toxicity 内源性大麻素系统在性腺发育中的作用：对内分泌干扰和生殖毒性的影响。

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-12-19 DOI: 10.1016/j.reprotox.2024.108822

Anderson Tadeu de Araújo-Ramos, Anderson Joel Martino-Andrade

The endocannabinoid system (ECS) plays a pivotal role in reproductive physiology, including gonadal development, though its influence on testis and ovary development has only recently gained attention. The ECS comprises lipid-derived ligands such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), along with cannabinoid receptors CB1 and CB2, which are expressed in various gonadal cells. Emerging research indicates that ECS signaling is critical for testosterone synthesis and gonadal cell proliferation and differentiation. This review explores the expression and function of ECS components in developing gonads, highlighting the differential roles of CB1 and CB2 receptors in species-specific contexts. Furthermore, the ECS has been suggested to be involved in the adverse effects of endocrine-disrupting chemicals (EDCs) on reproductive development. EDCs, such as phthalates, may interfere with ECS signaling, potentially leading to reproductive abnormalities that resemble the human Testicular Dysgenesis Syndrome (TDS). Understanding the molecular interactions between EDCs and the ECS could reveal novel mechanisms underlying reproductive toxicities. Future research should focus on the detailed localization and temporal expression of ECS components in fetal gonads, the mechanisms of cannabinoid-mediated testosterone inhibition, and the potential direct interaction of EDCs with the ECS. This knowledge could be crucial for developing strategies to mitigate reproductive health risks associated with EDC exposure.

内源性大麻素系统（ECS）在生殖生理，包括性腺发育中起着关键作用，尽管它对睾丸和卵巢发育的影响直到最近才得到关注。ECS包括脂质衍生的配体，如anandamide （AEA）和2-花生四烯醇甘油（2-AG），以及大麻素受体CB1和CB2，这些受体在各种性腺细胞中表达。新兴研究表明，ECS信号传导对睾酮合成和性腺细胞增殖和分化至关重要。本文探讨了ECS组分在性腺发育中的表达和功能，重点介绍了CB1和CB2受体在物种特异性背景下的不同作用。此外，ECS被认为与内分泌干扰物质（EDCs）对生殖发育的不利影响有关。邻苯二甲酸盐等EDCs可能干扰ECS信号，可能导致类似于人类睾丸发育不良综合征（TDS）的生殖异常。了解EDCs和ECS之间的分子相互作用可以揭示生殖毒性的新机制。未来的研究应集中在ECS组分在胎儿性腺中的详细定位和时间表达，大麻素介导的睾酮抑制机制，以及EDCs与ECS的潜在直接相互作用。这方面的知识对于制定战略以减轻与EDC接触有关的生殖健康风险至关重要。

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引用次数: 0

Evaluation of the effect of rozanolixizumab on pregnancy outcomes and pre- and postnatal development in cynomolgus monkeys 评价罗扎利单抗对食蟹猴妊娠结局及产前和产后发育的影响。

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-12-19 DOI: 10.1016/j.reprotox.2024.108823

Annick Cauvin , Kevin Brady , Joy Cavagnaro , C. Marc Luetjens

Rozanolixizumab, a humanised immunoglobulin (Ig) G4 monoclonal antibody that selectively inhibits binding of IgG to the neonatal Fc receptor (FcRn), was evaluated in an embryo–foetal enhanced pre- and postnatal development (ePPND) study. Pregnant female cynomolgus monkeys (19 per group) received subcutaneous rozanolixizumab 50 mg/kg or 150 mg/kg or vehicle every 3 days from gestation day 20 until delivery. The proportion of pregnancy losses was 15.8%, 21.1% and 5.3% in the rozanolixizumab 50 mg/kg, 150 mg/kg and control groups, respectively. Based on eNormograms for groups of 18 or 20 animals, these results were considered to be within the range of spontaneous prenatal losses naturally observed in cynomolgus monkeys. Foetal examinations revealed no treatment-related effects. All infants had normal postnatal development, although higher mortality was observed in female infants from the control group during the first 3 weeks. All infants were able to mount a normal immune response to keyhole limpet haemocyanin when vaccinated at the age of 4 months. Offspring from 150 mg/kg-treated mothers had very low IgG levels at birth, indicating blockade of maternal IgG transfer; infants from mothers who received 50 mg/kg had variable IgG levels at birth, with mothers who had developed significant anti-drug antibodies conferring maternal IgG transfer to varying degrees. Rates of infection in infants were similar across treatment groups. IgG levels in infants from rozanolixizumab-treated groups normalised within 2 months. Treatment of pregnant cynomolgus monkeys with the FcRn inhibitor rozanolixizumab had no adverse effects on pre- or postnatal development of offspring, including immune system development.

Rozanolixizumab是一种人源化免疫球蛋白（Ig） G4单克隆抗体，选择性抑制IgG与新生儿Fc受体（FcRn）的结合，在胚胎-胎儿增强产前和产后发育（ePPND）研究中进行了评估。怀孕的雌性食蟹猴（每组19只）从妊娠第20天至分娩，每3天皮下注射50mg/kg或150mg/kg的罗扎利单抗或载药。50mg/kg、150mg/kg和对照组的妊娠损失比例分别为15.8%、21.1%和5.3%。根据18组或20组动物的正形图，这些结果被认为是在食蟹猴自然观察到的自发产前损失范围内。胎儿检查未发现治疗相关效果。所有婴儿都有正常的产后发育，尽管在前3周观察到对照组女婴的死亡率较高。所有的婴儿在4个月大的时候都能对锁眼帽贝血色素产生正常的免疫反应。150mg/kg剂量母鼠的后代出生时IgG水平很低，表明母体IgG转移受阻；母亲接受50mg/kg剂量的婴儿出生时IgG水平不同，母亲产生明显的抗药物抗体使母体IgG转移程度不同。不同治疗组的婴儿感染率相似。罗扎那利单抗组婴儿的IgG水平在2个月内恢复正常。用FcRn抑制剂rozanolixizumab治疗怀孕食蟹猴对后代的产前或产后发育（包括免疫系统发育）没有不良影响。

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引用次数: 0

Embryotoxicity of statins and other prescribed drugs with reported off-target effects on cholesterol biosynthesis 他汀类药物和其他处方药的胚胎毒性，据报道这些药物对胆固醇的生物合成具有脱靶效应。

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-12-10 DOI: 10.1016/j.reprotox.2024.108820

Taryn Hartley , Hagir Abdelmagid , Zeenat Abdulsalam , Aliyah Mansion , Emily Howe , Daniel Ramirez , Kaylei White , Emmanuel Tadjuidje

Cholesterol plays pivotal cellular functions ranging from maintaining membrane fluidity to regulating cell-cell signaling. High cholesterol causes cardiovascular diseases, low cholesterol is linked to neuropsychiatric disorders, and inborn errors of cholesterol synthesis cause multisystem malformation syndromes. Statins lower cholesterol levels by inhibiting the first, rate-limiting reaction of the cholesterol biosynthesis pathway catalyzed by hydroxymethyl-glutaryl-Coenzyme A reductase (HMGCR). However, they have also been shown to interfere with cellular pathways that are unrelated to cholesterol synthesis. One of the last enzymes of cholesterol biosynthesis, 7-dehydrocholesterol reductase (DHCR7), is often mutated in the Smith-Lemli-Opitz syndrome (SLOS), a multisystem malformation syndrome. Strikingly, recent studies have shown that some prescribed psychotropic pharmaceuticals inhibit its activity. In this study, we used Xenopus laevis as a model organism to test the effects of 8 FDA-approved statins and selected prescribed psychotropic drugs on the developing vertebrate embryo. Drugs were tested at concentrations ranging from 0.1 µM to 50 µM. Embryos were exposed to the drugs from the blastula stage through the swimming tadpole stage with daily medium change. Our data show that statins are heterogenous with respect to their ability to cause embryonic lethality, with simvastatin, pitavastatin, lovastatin, cerivastatin, and fluvastatin being the most toxic ones. Observed phenotypes included delayed development, shortened body axis and pericardiac edema. On the other hand, psychotropic drugs were less embryonic lethal than statins but caused similar phenotypes as well as microcephaly and holoprosencephaly. Our findings suggest that the proximal and distal inhibition of cholesterol biosynthesis have different but overlapping effects on embryonic development.

胆固醇在细胞中发挥着至关重要的功能，从维持膜的流动性到调节细胞间的信号传递。高胆固醇会导致心血管疾病，低胆固醇与神经精神疾病有关，先天性胆固醇合成错误会导致多系统畸形综合征。他汀类药物通过抑制由羟甲基戊二酰辅酶 A 还原酶（HMGCR）催化的胆固醇生物合成途径中的第一个限速反应来降低胆固醇水平。不过，它们也被证明会干扰与胆固醇合成无关的细胞途径。胆固醇生物合成的最后一种酶--7-脱氢胆固醇还原酶（DHCR7）在史密斯-莱姆利-奥皮茨综合征（SLOS）（一种多系统畸形综合征）中经常发生突变。令人震惊的是，最近的研究表明，一些处方精神药物会抑制它的活性。在这项研究中，我们以爪蟾为模型生物，测试了 8 种美国食品及药物管理局批准的他汀类药物和部分处方精神药物对发育中的脊椎动物胚胎的影响。测试药物的浓度范围为 0.1µM 至 50µM。胚胎从胚泡期到游动蝌蚪期接触药物，每天更换培养基。我们的数据显示，他汀类药物导致胚胎死亡的能力各不相同，其中辛伐他汀、匹伐他汀、洛伐他汀、西立伐他汀和氟伐他汀的毒性最强。观察到的表型包括发育迟缓、体轴缩短和心包水肿。另一方面，精神药物对胚胎的致死率低于他汀类药物，但会导致类似的表型以及小头畸形和全脑畸形。我们的研究结果表明，胆固醇生物合成的近端和远端抑制对胚胎发育有不同但重叠的影响。

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引用次数: 0

Quaternary ammonium compound exposure causes infertility by altering endocrine signaling and gametogenesis 季铵化合物暴露通过改变内分泌信号和配子发生导致不育。

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-12-07 DOI: 10.1016/j.reprotox.2024.108817

Zachary A. Kirkpatrick , Vanessa E. Melin , Terry C. Hrubec

Quaternary ammonium compounds (QACs) are common substances utilized in cleaners, ophthalmic solutions, swimming pool treatments, cosmetics, and other consumer goods. Previous studies have shown that QAC exposure causes infertility in both male and female mice. Based on these studies, we hypothesized that oral QAC exposure negatively impacts male and female reproduction through changes in physiologic and endocrine mechanisms rather than direct toxicity to gametes. Endocrine disruption was assessed by evaluating luteinizing hormone (LH) and follicle stimulating hormone (FSH) concentrations in male and female mice exposed orally throughout gestation and lactation, and by changes in estrogen and progesterone in in orally exposed females throughout pregnancy. Sperm functionality and spermatogenesis were assessed by in vitro fertilization; while Sertoli cell homeostasis was evaluated by determining cellular metabolism, cell cycle progression and blood-testes barrier (BTB) permeability. QAC exposure decreased LH, and FSH concentrations in both males and females, and decreased progesterone and estrogen concentrations during pregnancy. QACs significantly decreased Sertoli cell metabolism at 0.0005 % ADBAC+DDAC well before disruption of the BTB at 0.01 %. Fertilization was not affected 24 h after exposure but was decreased after a 10 day rest period suggesting a disruption in spermatogenesis rather than direct toxicity to sperm. Lastly, QAC exposure altered Sertoli cell cycling with a G2/M cycle arrest. While the effect of QAC exposure on humans is unknown, implications from the in vivo and in vitro studies are concerning given the rise in infertility rates and increased reliance on assisted reproductive technologies along with ubiquitous exposure to QACs.

季铵化合物（QACs）是清洁剂、眼科溶液、游泳池护理、化妆品和其他消费品中常用的物质。先前的研究表明，接触QAC会导致雄性和雌性小鼠不孕。基于这些研究，我们假设口服QAC暴露通过生理和内分泌机制的改变而不是直接对配子产生毒性，从而对男性和女性的生殖产生负面影响。通过在整个妊娠期和哺乳期口服暴露的雄性和雌性小鼠中黄体生成素（LH）和促卵泡激素（FSH）的浓度，以及在整个妊娠期口服暴露的雌性小鼠中雌激素和黄体酮的变化来评估内分泌干扰。通过体外受精评估精子功能和精子发生；通过测定细胞代谢、细胞周期进展和血睾丸屏障（BTB）通透性来评估支持细胞稳态。妊娠期暴露于QAC可降低男性和女性的LH和FSH浓度，并降低孕酮和雌激素浓度。当ADBAC+DDAC浓度为0.0005%时，QACs显著降低了支持细胞的代谢，而当ADBAC+DDAC浓度为0.01%时，BTB则被破坏。暴露24小时后，受精不受影响，但在休息10天后，受精减少，这表明精子发生受到干扰，而不是直接对精子产生毒性。最后，QAC暴露改变了支持细胞周期，出现G2/M周期阻滞。虽然QAC暴露对人类的影响尚不清楚，但鉴于不孕率的上升和对辅助生殖技术的依赖增加以及QAC的普遍暴露，体内和体外研究的影响令人担忧。

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引用次数: 0

Maternal exposure to fine particulate matter in the air and risk for fetal congenital heart defects: A case-control study 母亲暴露于空气中的细颗粒物与胎儿先天性心脏缺陷的风险：一项病例对照研究。

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-12-03 DOI: 10.1016/j.reprotox.2024.108816

Zhao Li , Di Wang , Lei Jin , Jie Zhang , Tao Xue , Lei Jin

Prior research into the association between fine particulate matter (PM_2.5) exposure and the risk for fetal congenital heart defect (CHD) has yielded inconclusive and conflicting results. More epidemiologic evidence from different regions is necessary. A case-control study was conducted with 360 CHD cases and 3600 healthy newborns. Both the cases and the controls were registered by the mothers in the Prenatal Health Care System during the first trimester and gave birth at hospitals in the Tongzhou District of Beijing between 2013 and 2018. Information on PM_2.5 was obtained from satellite remote sensing monitoring data. We estimated average monthly PM_2.5 exposure for participants from 3 months before the last menstrual period through 6 months of gestational period. A logistic regression model was used to estimate odd ratio (OR) (95 % confidence interval, CI) for PM_2.5 exposure level and fetal risk for CHD. In our study, PM_2.5 concentrations before pregnancy and in the first trimester were not associated with CHD risk. In the second trimester, 2nd high quartile PM_2.5 group during the second month were associated with a lower CHD risk (adjusted OR(aOR)= 1.42, 95 % CI: 1.04–1.94) and highest quartile level group of PM_2.5 exposure in the third month were associated with a reduced risk for fetal CHD (aOR=0.70, 95 % CI: 0.51–0.97). After Bonferroni’s α correction, no comparisons were statistically significant. In conclusion, no associations were found between PM_2.5 exposure level and fetal risk for CHD in our study.

先前对细颗粒物（PM2.5）暴露与胎儿先天性心脏缺陷（CHD）风险之间关系的研究得出了不确定和相互矛盾的结果。需要更多来自不同地区的流行病学证据。对360例冠心病患者和3600例健康新生儿进行病例对照研究。这些病例和对照组都是在2013年至2018年期间在北京通州区的医院分娩的母亲在妊娠前三个月在产前保健系统中登记的。PM2.5信息来源于卫星遥感监测数据。我们估计了参与者从最后一次月经前3个月到妊娠期6个月的平均每月PM2.5暴露量。采用logistic回归模型估计PM2.5暴露水平与胎儿冠心病风险的奇比（OR）（95%置信区间，CI）。在我们的研究中，怀孕前和妊娠早期的PM2.5浓度与冠心病风险无关。在妊娠中期，第二个月PM2.5第二高四分位数组与较低的CHD风险相关（调整OR(aOR)=1.42, 95% CI: 1.04-1.94），第三个月PM2.5暴露最高四分位数组与较低的胎儿CHD风险相关（aOR=0.70, 95% CI: 0.51-0.97）。经Bonferroni α校正后，比较无统计学意义。总之，在我们的研究中没有发现PM2.5暴露水平与胎儿冠心病风险之间的关联。

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引用次数: 0

Detection and quantification of microplastics in endometrial polyps and their role in polyp formation 子宫内膜息肉中微塑料的检测和定量及其在息肉形成中的作用。

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-11-29 DOI: 10.1016/j.reprotox.2024.108757

Shilin He , Yanling Zhang

With the increasing use of plastics, microplastic (MPs) pollution has garnered significant attention in recent years. Endometrial polyps are prevalent gynecological conditions in women of childbearing age, which impair endometrial receptivity and contribute to female infertility. However, no studies have yet reported the exposure of endometrial polyps to MPs. This study employed pyrolysis-gas chromatography/mass spectrometry and laser direct infrared spectroscopy to detect and compare MPs between normal endometrium and endometrial polyps. Using Py-GC/MS, we identified three main MPs in 14 normal endometrial samples and 16 endometrial polyps. The average abundance of MPs in the endometrial polyp group was significantly higher than in the normal endometrium group. The respective average abundance of polyethylene (PE), polystyrene (PS), and polyvinyl chloride (PVC) in the polyp and normal endometrium groups was 13.66 ± 2.0 vs. 7.132 ± 0.78 μg/g (p = 0.0009), 94.81 ± 10.67 vs. 69.29 ± 6.93 μg/g, and 67.67 ± 11.02 vs. 56.35 ± 6.90 μg/g. LDIR analysis revealed 13 different types of MPs, with polymethylmethacrylate being the most prevalent. Moreover, we discovered that PS microspheres can promote the proliferation and migration of endometrial stromal cells through PI3K/AKT pathway, which may be a key factor in the formation of endometrial polyps. This study is the first to explore the presence of MPs in endometrial polyps, compare the differences in MPs content between normal endometrium and endometrial polyps, and clarify the potential connection between MPs exposure and the formation of endometrial polyps. Further research is required to explore additional potential insights.

近年来，随着塑料使用量的增加，微塑料污染引起了人们的广泛关注。子宫内膜息肉是育龄妇女常见的妇科疾病，它损害子宫内膜容受性，导致女性不孕。然而，尚未有研究报道子宫内膜息肉暴露于MPs。本研究采用热解-气相色谱/质谱法和激光直接红外光谱法检测和比较正常子宫内膜和子宫内膜息肉的MPs。我们在14例正常子宫内膜和16例子宫内膜息肉中鉴定出3种主要的MPs。子宫内膜息肉组MPs的平均丰度明显高于正常子宫内膜组。各自的平均丰度聚乙烯(PE)、聚苯乙烯(PS)和聚氯乙烯(PVC)息肉和正常子宫内膜组是13.66 ±  2.0和7.132±0.78  μg / g (p = 0.0009),94.81 ±  10.67和69.29±6.93  μg / g和67.67 ±  11.02和56.35±6.90  μg / g。LDIR分析揭示了13种不同类型的MPs，其中聚甲基丙烯酸甲酯是最普遍的。此外，我们发现PS微球可以通过PI3K/AKT通路促进子宫内膜基质细胞的增殖和迁移，这可能是子宫内膜息肉形成的关键因素。本研究首次探讨了MPs在子宫内膜息肉中的存在，比较了正常子宫内膜与子宫内膜息肉中MPs含量的差异，阐明了MPs暴露与子宫内膜息肉形成之间的潜在联系。需要进一步的研究来探索其他潜在的见解。

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引用次数: 0

Prenatal developmental toxicity evaluation of higher olefins in Sprague-Dawley rats 高烯烃对Sprague-Dawley大鼠产前发育毒性评价

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-11-29 DOI: 10.1016/j.reprotox.2024.108756

Quan Shi , Michael G. Penman , Juan-Carlos Carrillo , Jamie Dunn , Hua Shen , Sophie Jia , An R. Van Rompay , Fabienne Hubert , Peter J. Boogaard

Higher olefins (HO) are used primarily as intermediates in the production of other chemicals, such as polymers, fatty acids, plasticizer alcohols, surfactants, lubricants, amine oxides and detergent alcohols. The potential prenatal developmental toxicity of five HO (i.e. Hex-1-ene, Nonene, branched, Octadec-1-ene, and Hydrocarbons, C12–30, olefin-rich, ethylene polymn. by product) were evaluated in prenatal development toxicity studies (OECD TG 414 (2001)) in Sprague-Dawley rats as part of the regulatory requirements for REACH registration. In each study, the HO were administered by gavage at dose levels of 0, 100, 300 and 1000 mg/kg bw/day from Day 3 to Day 19 of gestation. Maternal food consumption, body weights, and clinical signs were monitored throughout gestation. The rats were sacrificed on Day 20 of gestation and examined for standard parameters of reproductive performance (number of corpora lutea, number of implantations, pre- and post-implantation loss, number of live- and dead fetuses, sex-ratio and the weight of the reproductive organs). The fetuses were weighed and examined for external, visceral, and skeletal variations and malformations. The results from these studies showed that none of the HO treated groups showed maternal or embryo–fetal toxicity. Although occasionally incidental skeletal and visceral malformations were observed with Hex-1-ene and Octadec-1-ene, these findings were found to be spontaneous, unrelated to treatment and not indicative for any disturbance of fetal development. In conclusion, the No-Observed-Adverse-Effect Level (NOAEL) for all tested HO was determined to be 1000 mg/kg bw/day, which is the highest dose level administered, for both maternal and developmental toxicity.

高烯烃（HO）主要用作生产其他化学品的中间体，如聚合物、脂肪酸、增塑剂醇、表面活性剂、润滑剂、胺氧化物和洗涤剂醇。五种HO（即己烯、壬烯、支链、十八烯、碳氢化合物、C12-30、富烯烃、乙烯聚合物）的潜在产前发育毒性。作为REACH注册监管要求的一部分，在Sprague-Dawley大鼠的产前发育毒性研究（OECD TG 414(2001)）中对其进行了评估。在每项研究中，从妊娠第3天至第19天，分别以0、100、300和1000 mg/kg bw/天的剂量给药。在整个妊娠期间监测产妇的食物消耗、体重和临床症状。在妊娠第20天处死大鼠，检查其生殖性能的标准参数（黄体数、着床数、着床前后损失、活胎数和死胎数、性别比和生殖器官重量）。对胎儿进行称重并检查其外部、内脏和骨骼的变异和畸形。这些研究的结果表明，没有一个HO处理组表现出母体或胚胎-胎儿毒性。虽然偶尔会观察到六烯和十八烯引起的骨骼和内脏畸形，但这些发现是自发的，与治疗无关，也不表明胎儿发育有任何障碍。总之，所有测试的HO的未观察到的不良反应水平（NOAEL）被确定为1000 mg/kg bw/day，这是对母体和发育毒性的最高剂量水平。

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引用次数: 0

Oxidative stress and energy metabolism in male reproductive damage from single and combined high-power microwave exposure at 1.5 and 4.3GHz 1.5和4.3Ghz单次和联合高功率微波暴露对男性生殖损伤的氧化应激和能量代谢

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-11-29 DOI: 10.1016/j.reprotox.2024.108759

Yanyang Li , Binwei Yao , Junqi Men , Yueyue Pang , Jingchao Gao , Yanxin Bai , Hui Wang , Jing Zhang , Li Zhao , Xinping Xu , Ji Dong , Congsheng Li , Ruiyun Peng

The effect of multi-frequency electromagnetic environments on male reproduction has attracted the medical community’s interest. Studies have investigated the effects and mechanisms of single-frequency microwave exposure on male reproduction, but comparative research on high-power microwave (HPM) composite and single exposure remains scarce. This study aimed to examine the effects and mechanisms of combined 1.5 GHz and 4.3 GHz microwave exposure on male reproduction. Male Wistar rats were exposed to 1.5 GHz (L-band) and 4.3 GHz (C-band) electromagnetic radiation for 15 minutes. The four groups were: sham, 10 mW/cm² L-band, 10 mW/cm² C-band, and 5 mW/cm² L-band and 5 mW/cm² C-band compound. Assessments were made on the pathological structures of testes, sperm viability, serum sex hormones, oxidative stress, and energy metabolism levels after radiation. Exposure to 1.5 GHz and 4.3 GHz microwaves individually resulted in testicular tissue damage and reduced sperm quality. There was little difference between the damage caused by HPM composite and single exposure. The exposed groups showed histological and ultrastructural changes, with reduced spermatozoa viability, motility parameters, and serum testosterone, luteinizing hormone, follicle-stimulating hormone, and serum inhibin-B on days 1 and 7 after exposure. These tended to recover partially by day 14. Adenosine triphosphate content and lactate dehydrogenase and succinate dehydrogenase activities in the exposed testicular tissue decreased, corresponding to decreased superoxide dismutase activity and increased malondialdehyde content. Both single and combined exposure to L- and C-band HPM affect the male reproductive system. Exposure to single and compound HPM shows no significant difference in risks, with oxidative stress and energy metabolism disturbances playing key roles.

多频电磁环境对男性生殖的影响引起了医学界的关注。单频微波暴露对男性生殖的影响和机制已有研究，但对高功率微波复合辐射和单次微波暴露的比较研究还很少。本研究旨在探讨1.5GHz和4.3GHz微波联合暴露对男性生殖的影响及其机制。雄性Wistar大鼠分别暴露于1.5GHz （l波段）和4.3GHz （c波段）电磁辐射15min。四组分别为：假药组、10mW/cm²l波段组、10mW/cm²c波段组、5mW/cm²l波段和5mW/cm²c波段复合组。评估放疗后睾丸病理结构、精子活力、血清性激素、氧化应激和能量代谢水平。分别暴露在1.5GHz和4.3GHz的微波下会导致睾丸组织损伤和精子质量下降。HPM复合材料与单次暴露的损伤差异不大。暴露组在暴露后第1天和第7天出现组织学和超微结构变化，精子活力、运动参数以及血清睾酮、促黄体生成素、促卵泡激素和血清抑制素- b均下降。这些在第14天有部分恢复的趋势。暴露后睾丸组织中三磷酸腺苷含量降低，乳酸脱氢酶和琥珀酸脱氢酶活性降低，对应于超氧化物歧化酶活性降低，丙二醛含量升高。L-和c -波段HPM的单独和联合暴露都会影响男性生殖系统。暴露于单一和复合HPM的风险无显著差异，氧化应激和能量代谢紊乱起关键作用。

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引用次数: 0

Evaluation of cytoprotective effects of cannabidiol on neuroinflammation and neurogenesis process in rat offsprings 大麻二酚对大鼠后代神经炎症和神经发生过程的细胞保护作用评价。

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-11-29 DOI: 10.1016/j.reprotox.2024.108761

Deniz Catakli , Yalcin Erzurumlu , Halil Asci , Mehtap Savran , Serdar Sezer

Natural compounds include complex chemical compounds that exist in plants, animals and microbes. Due to their broad spectrum of pharmacological and biochemical actions, they have been widely used to treat multifactorial diseases, including cancer. In addition, their demonstrated neuroprotective properties strongly support their use in the treatment of neurological diseases. The present study investigated the effect of cannabidiol (CBD), which can easily cross the placental barrier and is known to have anti-inflammatory effects, on fetal neuroinflammation and neurogenesis in a systemic inflammation model during pregnancy. Herein, 12 weeks adult pregnant rats (n = 30) were randomly divided into 5 groups with 6 rats in each group as follows: Control, LPS (lipopolysaccharide, i.p.), LPS+CBD 5 mg/kg (i.p.), LPS+CBD10 mg/kg (i.p.) and LPS+CBD30 mg/kg (i.p.). After the injections, blood samples of rats were collected, fetuses and placentas were taken by hysterectomy. Histopathological analysis, immunohistochemical staining, ELISA and immunoblotting analysis were performed to investigate neuroinflammatory and neurogenesis parameters in fetal brain and placenta tissues. Our findings indicated that CBD administration importantly suppressed the inflammatory process in the rat fetal brain by decreasing interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels and diminishing nuclear factor kappa B (NF-κB) activation. Moreover, CBD inhibited lipopolysaccharide (LPS)-induced increasing levels of neuroinflammation-associated proteins, including glial fibrillary acidic protein (GFAP), S100B and cAMP-response element binding protein (CREB). These results suggest that CBD usage in pregnancy with inflammation conditions may be an effective therapeutic option for preventing conditions that may cause neuroinflammation in the fetal brain and adversely affect neurogenesis.

天然化合物包括存在于植物、动物和微生物中的复杂化合物。由于其广泛的药理和生化作用，它们已被广泛用于治疗包括癌症在内的多因素疾病。此外，它们所显示的神经保护特性有力地支持了它们在神经系统疾病治疗中的应用。在妊娠期全身性炎症模型中，本研究研究了CBD对胎儿神经炎症和神经发生的影响，CBD可以很容易地穿过胎盘屏障，并且已知具有抗炎作用。将12周龄成年妊娠大鼠（n=30）随机分为5组，每组6只，分别为对照组、LPS（脂多糖）、LPS+CBD 5mg/kg （i.p.）、LPS+CBD10 mg/kg （i.p.）和LPS+CBD30 mg/kg （i.p.）。注射后取大鼠血样，切除子宫取胎儿和胎盘。采用组织病理学分析、免疫组织化学染色、ELISA和免疫印迹法观察胎脑和胎盘组织的神经炎症和神经发生参数。我们的研究结果表明，CBD通过降低白细胞介素-1β (IL-1β)和肿瘤坏死因子-α (TNF-α)水平和减少核因子κB （NF-κB）的激活来抑制大鼠胎脑的炎症过程。此外，CBD抑制脂多糖（LPS）诱导的神经炎症相关蛋白水平升高，包括胶质纤维酸性蛋白（GFAP）、S100B和camp反应元件结合蛋白（CREB）。这些结果表明，在患有炎症的孕妇中使用CBD可能是一种有效的治疗选择，可以预防可能导致胎儿大脑神经炎症并对神经发生产生不利影响的疾病。

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引用次数: 0