Reproductive toxicology最新文献_第2页

Role of Rab proteins in PFOA-induced changes in boar sperm motility and capacitation Rab 蛋白在 PFOA 诱导的公猪精子活力和获能变化中的作用。

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-11-05 DOI: 10.1016/j.reprotox.2024.108745

Seung-Ik Jang , Jae-Hwan Jo , Claudine Uwamahoro , Eun-Ju Jung , Woo-Jin Lee , Jeong-Won Bae , Sangsu Shin , Sang In Lee , Myoung Ok Kim , Joonho Moon , Woo-Sung Kwon

Perfluorooctanoic acid (PFOA), a pervasive environmental contaminant, elicits adverse effects on sperm functions, including sperm motility and capacitation status. However, the specific mechanisms by which PFOA disrupts sperm functions during capacitation remain poorly elucidated. Therefore, this study aimed to investigate the molecular mechanisms underlying the PFOA-induced inhibition of sperm motility and capacitation in boar spermatozoa by focusing on Ras-related (Rab) proteins, which regulate membrane trafficking and play key roles in male sperm development, acrosome formation, and the acrosome reaction. Results showed significant reductions in sperm motility and various kinematic parameters following PFOA exposure. Correlation analysis revealed that Rab14 was positively correlated with dance mean (DNM) and negatively correlated with wobble (WOB), indicating that PFOA might affect sperm motility through Rab14 and potentially lead to reduced pregnancy rates. Differences in Rab25 were positively correlated with differences in total motility (MOT), progressive motility (PRG), linearity (LIN), and mean angular displacement (MAD), suggesting that PFOA might influence sperm motility by altering Rab25. Differences in Rab34 were positively correlated with differences in acrosome-reacted spermatozoa, implicating its role in the acrosome reaction. These findings provided insights into the molecular mechanism of PFOA-induced reproductive toxicity and highlighted the function of Rab proteins as biomarkers for the assessment of the effects of similar environmental toxins on male fertility.

全氟辛酸（PFOA）是一种普遍存在的环境污染物，会对精子功能（包括精子活力和获能状态）产生不利影响。然而，PFOA 在获能过程中破坏精子功能的具体机制仍未得到充分阐明。因此，本研究旨在通过重点研究 Ras 相关蛋白（Rab），探讨 PFOA 诱导的公猪精子运动和获能能力抑制的分子机制。结果表明，暴露于 PFOA 后，精子的运动能力和各种运动参数都明显下降。相关分析表明，Rab14与舞动平均值（DNM）呈正相关，而与摆动值（WOB）呈负相关，这表明PFOA可能会通过Rab14影响精子的运动能力，并可能导致受孕率降低。Rab25的差异与总运动能力（MOT）、渐进运动能力（PRG）、线性度（LIN）和平均角位移（MAD）的差异呈正相关，表明PFOA可能通过改变Rab25来影响精子的运动能力。Rab34的差异与顶体反应精子的差异呈正相关，表明其在顶体反应中的作用。这些发现深入揭示了 PFOA 诱导生殖毒性的分子机制，并强调了 Rab 蛋白作为生物标志物的功能，可用于评估类似环境毒素对男性生育能力的影响。

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引用次数: 0

Preliminary study on the impact of 900 MHz radiation on human sperm: An in vitro molecular approach 关于 900 MHz 辐射对人类精子影响的初步研究：体外分子方法

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-11-05 DOI: 10.1016/j.reprotox.2024.108744

İ. Keskin , S. Karabulut , A.A. Kaplan , M. Alagöz , M. Akdeniz , K.K. Tüfekci , D.L. Davis , S. Kaplan

The use of technologies that produce and emit electromagnetic fields (EMF) is growing exponentially worldwide. The biological effects of EMF-emitting equipment, such as mobile phones and other wireless devices, have been studied in the last decade using in vitro and in vivo methods. Infertility is a growing health problem, and nearly half of cases are because of male-factor. This study investigated the direct in vitro effects of 900 MHz radiation exposure on sperm parameters, genetic status, apoptotic markers, and the PI3K/AKT signaling pathway in healthy normozoospermic men. Semen samples were divided into four groups, two control (30 min and 1 h) and two EMF exposure (30 min and 1 h). Sperm parameters (motility, progressive motility, acrosomal index, morphology), genetic status (DNA fragmentation and chromatin integrity), apoptotic markers (cytokine-c and caspase-3 expression) and the PI3K/AKT signaling pathway (phosphoinoitide 3-kinase-PI3K- and phosphorylated AKT- p-AKT-) were analysed. Sperm motility were significantly reduced in 30 min EMF exposure while a significant increase in the expression of p-AKT were observed in 1 h EMF exposure group. An increased vacuolisation, acrosomal defect, extension of subacrosomal space, uncondensed chromatin structure, apoptotic signs and disrupted axoneme were observed in both EMF groups which were not observed in the control group. Other sperm parameters (morphology and acrosomal index), genetic status, apoptotic markers and the PI3K expression rates had no significant change.

在全球范围内，产生和发射电磁场（EMF）技术的使用呈指数级增长。近十年来，人们利用体外和体内方法研究了移动电话和其他无线设备等电磁场辐射设备对生物的影响。不孕不育是一个日益严重的健康问题，近一半的病例是由于男性因素造成的。本研究调查了 900 MHz 辐射对健康正常无精子男性的精子参数、遗传状态、凋亡标志物和 PI3K/AKT 信号通路的直接体外影响。精液样本分为四组，两组为对照组（30 分钟和 1 小时），两组为暴露于电磁场组（30 分钟和 1 小时）。对精子参数（运动能力、渐进运动能力、顶体指数、形态）、遗传状态（DNA片段化和染色质完整性）、凋亡标志物（细胞因子-c和caspase-3表达）和PI3K/AKT信号通路（磷酸化亚硝基3-激酶-PI3K-和磷酸化AKT- p-AKT-）进行了分析。暴露于电磁场30分钟后，精子活力明显降低，而暴露于电磁场1小时后，p-AKT的表达明显增加。EMF组和对照组均未观察到精子空泡化、顶体缺陷、顶体下空间扩展、染色质结构不凝结、凋亡迹象和轴丝中断等现象。其他精子参数（形态和顶体指数）、遗传状态、凋亡标志物和 PI3K 表达率均无明显变化。

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引用次数: 0

Exploring the ameliorative potential of rutin against High-Sucrose Diet-induced oxidative stress and reproductive toxicity in Drosophila melanogaster 探索芦丁对高蔗糖饮食诱导的黑腹果蝇氧化应激和生殖毒性的改善潜力

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-11-05 DOI: 10.1016/j.reprotox.2024.108742

Abhratanu Ganguly , Sayantani Nanda , Moutushi Mandi , Kanchana Das , Prem Rajak

Sucrose is a vital ingredient in numerous food items consumed regularly. However, exposure to excessive sucrose for a prolonged period can promote health issues. The reproductive system has a delicate physiology that can be targeted by various chemical stressors, including sucrose. Hence, the present in vivo study aims to unveil the impacts of High-Sucrose Diet (HSD) on the reproductive fitness of Drosophila melanogaster. In addition, the present work has also assessed the protective potential of a bioactive compound, rutin, against it. Here, first instar larvae were exposed to HSD (30 %) alone and in combination with rutin (100–300 µM) till their adult stage. HSD disturbed sex comb morphology in adult males, while fecundity and hatchability of eggs in females. Moreover, HSD triggered gonadal ROS production, oxidative stress, and modulated endogenous antioxidants such as SOD, catalase, and glutathione in both sexes. Nuclear fragmentation and tissue injuries, along with protein and lipid oxidation, were also apparent. Elevated levels of cytosolic Iron suggested an active Fenton reaction in adults. Further, HSD modulated the activities of reproductive and metabolic mediators, including vitellogenin, malate dehydrogenase, glucose-6-phosphate dehydrogenase, and angiotensin-converting enzymes that are critical to maintain the overall reproductive fitness. Interestingly, co-treatment with rutin, mainly at 200 µM, mitigated these adverse effects and restored reproductive fitness. The protective potential of rutin might be attributed to its ability to normalize redox homeostasis, reduce oxidative stress, and optimize critical enzymes involved in reproductive physiology. These findings suggest that rutin has potential therapeutic implications for counteracting the reproductive hazards induced by HSD.

蔗糖是许多经常食用的食品中的重要成分。然而，长期接触过量的蔗糖会引发健康问题。生殖系统具有微妙的生理机能，可能会受到包括蔗糖在内的各种化学压力的影响。因此，本体内研究旨在揭示高蔗糖饮食（HSD）对黑腹果蝇生殖健康的影响。此外，本研究还评估了一种生物活性化合物芦丁对高蔗糖饮食的保护潜力。在本研究中，1龄幼虫单独或与芦丁（100-300µM）一起暴露于 HSD（30%），直至成虫阶段。HSD干扰了雄性成虫的性梳形态，同时也影响了雌性成虫的受精率和卵的孵化率。此外，HSD 还会引发生殖腺产生 ROS 和氧化应激，并调节雌雄雌鸟的内源性抗氧化剂，如 SOD、过氧化氢酶和谷胱甘肽。核破碎和组织损伤以及蛋白质和脂质氧化也很明显。细胞铁水平的升高表明成人的芬顿反应活跃。此外，HSD 还调节了生殖和代谢介质的活性，包括卵黄素、苹果酸脱氢酶、葡萄糖-6-磷酸脱氢酶和血管紧张素转换酶，这些介质对整体生殖健康至关重要。有趣的是，与芦丁（主要是 200µM 的芦丁）联合处理可减轻这些不利影响并恢复生殖能力。芦丁的保护潜力可能归因于它能使氧化还原平衡正常化、减少氧化应激和优化参与生殖生理的关键酶。这些研究结果表明，芦丁具有潜在的治疗意义，可对抗 HSD 诱导的生殖危害。

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引用次数: 0

Retrospective cumulative dietary risk assessment of craniofacial alterations by residues of pesticides 对农药残留导致颅面改变的累积膳食风险进行回顾性评估。

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-10-31 DOI: 10.1016/j.reprotox.2024.108741

Luc Mohimont , Chris Anagnostopoulos , Maria Anastassiadou , Anna Federica Castoldi , Adeline Cavelier , Tamara Coja , Peter Craig , Federica Crivellente , Bruno Dujardin , Andy Hart , Wim Hooghe , Samira Jarrah , Kyriaki Machera , Elena Menegola , Francesca Metruccio , Christian Sieke

In 2022, the European Food Safety Authority (EFSA) conducted a dietary cumulative risk assessment for active substances of plant protection products on two types of craniofacial alterations: 1) craniofacial alterations due to abnormal skeletal development and 2) head soft tissue alterations and brain neural tube defects. These effects were selected based on developmental biology knowledge and a hypothetical teratogenic process. Cumulative risk assessment was conducted for 14 European populations of women in childbearing age. The dietary cumulative exposure was determined using individual consumption data collected under national food consumption surveys, and the calculations were based on occurrence data collected by Member States under their official monitoring programmes. A rigorous uncertainty analysis was performed using expert knowledge elicitation. Considering all sources of uncertainty, their dependencies, and differences between populations, it was concluded that the total margin of exposure (MOET) resulting from cumulative exposure to residues of pesticides is above 100 for both types of craniofacial alterations and therefore the threshold for regulatory consideration is not exceeded. For the head soft tissue alterations and brain neural tube defects the MOET was even above 500 while for the alterations due to abnormal skeletal development, it was found about as likely as not that the MOET is above 500 in most populations. These results need to be interpreted in the light of the conservatism of the hazard assessment methodology. This review is a summary of the EFSA report on a retrospective cumulative dietary risk assessment of craniofacial alterations by residues of pesticides published in 2022.

2022 年，欧洲食品安全局（EFSA）对两种类型的颅面改变进行了植物保护产品活性物质的膳食累积风险评估：1）骨骼发育异常导致的颅面改变；2）头部软组织改变和脑神经管缺陷。这些影响是根据发育生物学知识和假设的致畸过程选定的。对 14 个欧洲育龄妇女群体进行了累积风险评估。膳食累积暴露量是根据国家食品消费调查中收集的个人消费数据确定的，而计算则是基于成员国在其官方监测计划中收集的发生数据。采用专家知识征询法进行了严格的不确定性分析。考虑到所有不确定性来源、它们之间的依赖关系以及不同人群之间的差异，得出结论认为，对于两种类型的颅颌面改变而言，农药残留累积暴露所产生的总暴露阈值1 （MOET）均高于 100，因此没有超出监管考虑的阈值。对于头部软组织改变和脑神经管缺陷，MOET 甚至高于 500，而对于骨骼发育异常引起的改变，大多数人群的 MOET 都高于 500。需要根据危害评估方法的保守性来解释这些结果。本综述是欧洲食物安全局于 2022 年发布的关于农药残留导致颅颌面改变的回顾性累积膳食风险评估报告的摘要。

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引用次数: 0

Whole mount preparation and analysis of rabbit mammary gland 兔乳腺的整装制备和分析。

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-10-29 DOI: 10.1016/j.reprotox.2024.108740

Harshal Rawtani , Julia Jackson , Fumei Gao , Namya Mellouk , Isabella Myer , Karina Cuevas Mora , Suzanne E. Fenton , Liping Feng

The mammary gland undergoes dynamic structural and compositional changes throughout life, influenced significantly by hormonal fluctuations and environmental factors. From embryonic development through menopause, this tissue adapts to accommodate phases such as postnatal expansion, pregnancy-induced lactation, and post-weaning involution. Hormones, growth factors, cytokines, and exogenous factors regulate these innate processes, affecting mammary epithelial cell proliferation and sensitivity, particularly in terminal end buds (TEB) and lobules, which are highly susceptible to endocrine disruption. Rodent models have provided invaluable insights into mammary gland biology, yet differences exist compared to human development, prompting the exploration of alternative models like rabbits. Additionally, there is momentum to move away from the use of nonhuman primates in safety assessments, increasing the need for evaluation tools for all tissues in the rabbit model. Rabbit mammary glands exhibit similarities to humans, making them promising for studying breast biology and pathology. However, protocols for whole-mount analysis of rabbit mammary glands are lacking due to the technical challenges of working with thicker tissue than rodent mammary glands. Here, we developed a methodology modified from rodent studies for preparing and analyzing rabbit mammary gland whole mounts, which is essential for advancing research in mammary gland biology and understanding the effects of hormonal and toxicant-induced disruption of mammary gland growth and function.

乳腺的结构和组成在人的一生中会发生动态变化，主要受激素波动和环境因素的影响。从胚胎发育到更年期，乳腺组织要适应产后扩张、妊娠引起的泌乳和断奶后内陷等阶段。激素、生长因子、细胞因子和外源性因子调节这些先天性过程，影响乳腺上皮细胞的增殖和敏感性，尤其是极易受内分泌干扰的末端末芽（TEB）和小叶。啮齿类动物模型为乳腺生物学提供了宝贵的见解，但与人类发育相比仍存在差异，这促使人们探索兔子等替代模型。此外，在安全性评估中不再使用非人类灵长类动物的趋势也在不断发展，因此更需要针对兔子模型中所有组织的评估工具。兔乳腺与人类相似，因此很有希望用于研究乳腺生物学和病理学。然而，与啮齿类动物乳腺相比，兔乳腺组织更厚，技术难度更大，因此缺乏对兔乳腺进行整装分析的方案。在这里，我们开发了一种从啮齿类动物研究中修改而来的方法，用于制备和分析兔乳腺全装片，这对于推进乳腺生物学研究以及了解激素和毒物引起的乳腺生长和功能紊乱的影响至关重要。

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引用次数: 0

Long-term subculture induces syncytialization and influent the response to bisphenol A (BPA) of placental JEG-3 cells 长期亚培养可诱导胎盘 JEG-3 细胞合胞化，并影响其对双酚 A (BPA) 的反应。

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-10-28 DOI: 10.1016/j.reprotox.2024.108738

Yu-Shiuan Huang , Ai-An Chang , Zhi-Jie Yang , Jung-An Chen , Chi-Kang Lin , Hsin-Chieh Lan

The placenta is a temporary organ that exists only during pregnancy, responsible for connecting the mother and the fetus. During placental development, the cytotrophoblast cells differentiate into multinucleated, syncytialized cells that envelop the chorionic villi, a process known as syncytialization. These syncytiotrophoblast cells serve as a barrier between maternal circulation and the fetus and secrete important hormones such as human chorionic gonadotropin (hCG), estrogen, and progesterone. Proper regulation of trophoblast differentiation and hormone secretion is crucial throughout pregnancy, as disruption of these processes can lead to pregnancy failure. Previous studies showed that Bisphenol A (BPA), an endocrine-disrupting chemical (EDC), negatively impacts pregnancy. It affects placental development, tissue morphology, hormone secretion, and probably increase the risk of pregnancy complications. Furthermore, some compounds like hCG and forskolin induce the cell differentiation and affecting hormone secretion in trophoblast. In this study, we found that long-term subculture of JEG-3 cells indicates an increase in cell differentiation, alterations in physiological properties, and changes in hormone secretion profiles. Our results also demonstrate distinct responses in JEG-3 cells to BPA stimulation in later passages, suggesting that long-term subculture alters cell characteristics and elicits varied responses to stimuli. This implies potential harm from BPA exposure at different stages of pregnancy, albeit through different mechanisms.

胎盘是怀孕期间才存在的临时器官，负责连接母亲和胎儿。在胎盘发育过程中，滋养细胞分化成多核的合胞化细胞，包裹着绒毛，这一过程被称为合胞化。这些合胞滋养层细胞是母体血液循环和胎儿之间的屏障，并分泌重要的激素，如人绒毛膜促性腺激素（hCG）、雌激素和孕酮。滋养层细胞分化和激素分泌的适当调节在整个孕期都至关重要，因为这些过程受到破坏会导致妊娠失败。它会影响胎盘发育、组织形态和激素分泌，并可能增加妊娠并发症的风险。此外，一些化合物（如 hCG 和福斯克林）会诱导滋养层细胞分化并影响激素分泌。在这项研究中，我们发现长期亚培养 JEG-3 细胞会导致细胞分化增加、生理特性改变和激素分泌曲线变化。我们的研究结果还表明，JEG-3 细胞在后期培养过程中对双酚 A 刺激的反应各不相同，这表明长期亚培养会改变细胞特性，并引起对刺激的不同反应。这意味着在怀孕的不同阶段接触双酚 A 可能会造成危害，尽管是通过不同的机制造成的。

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引用次数: 0

Genetic evidence linking retinol to birth weight: A two-sample Mendelian randomization study 视黄醇与出生体重有关的遗传学证据：一项双样本孟德尔随机研究。

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-10-28 DOI: 10.1016/j.reprotox.2024.108739

Fangxiang Mu, Kexin Wang, Lu Jiang, Fang Wang

This study aims to clarify the potential causal effects of dietary antioxidant vitamins on pregnancy outcomes (miscarriage, preterm labor, and birth weight) using Mendelian randomization (MR). Our instrumental variables (IVs) were single-nucleotide polymorphisms (SNPs) linked to retinol, vitamin C, carotene, and vitamin E (P < 5×10⁻⁶). The summary statistics for miscarriage, preterm labor, and birth weight were extracted from genome-wide association studies (GWASs), with a sample size of 56,172, 5480, and 261,932, respectively. The present MR study primarily used the inverse-variance weighted method, with additional sensitivity analyses conducted to evaluate the robustness of the findings. We found that retinol was closely related to the birth weight (β=0.091, 95 %CI: 0.009–0.172, P=0.028), and sensitivity analyses showed similar results (MR-RAPS: OR=1.101, 95 %CI: 1.027–1.180; maximum likelihood: OR=1.098, 95 %CI: 1.011–1.194). While the relationship of retinol with miscarriage or preterm labor was not statistically significant. Additionally, our study did not reveal an association between the carotene, vitamin E, and vitamin C and pregnancy-related outcomes, miscarriage, preterm labor, and birth weight (all P > 0.05). In conclusion, our findings indicated a causal effect between retinol and birth weight and suggested that maintaining retinol at normal levels during pregnancy can prevent low birth weight. Therefore, it would be beneficial to measure retinol levels in pregnant women and to supplement with vitamin A in cases of deficiency, as these could be valuable strategies for improving pregnancy outcomes.

本研究旨在利用孟德尔随机法（MR）阐明膳食抗氧化维生素对妊娠结局（流产、早产和出生体重）的潜在因果效应。我们的工具变量（IV）是与视黄醇、维生素 C、胡萝卜素和维生素 E 相关的单核苷酸多态性（SNPs）（P < 5×10-6）。流产、早产和出生体重的汇总统计数据来自全基因组关联研究（GWAS），样本量分别为 56 172、5 480 和 261 932。本磁共振研究主要采用逆方差加权法，并进行了额外的敏感性分析，以评估研究结果的稳健性。我们发现视黄醇与出生体重密切相关（β=0.091，95%CI：0.009-0.172，P=0.028），敏感性分析显示了类似的结果（MR-RAPS：OR=1.101，95%CI：1.027-1.180；最大似然法：OR=1.098，95%CI：1.011-1.194）。而视黄醇与流产或早产的关系并无统计学意义。此外，我们的研究没有发现胡萝卜素、维生素 E 和维生素 C 与妊娠相关结果、流产、早产和出生体重之间存在关联（所有 P > 0.05）。总之，我们的研究结果表明视黄醇与出生体重之间存在因果关系，并表明孕期视黄醇维持在正常水平可预防低出生体重。因此，测量孕妇的视黄醇水平并在缺乏维生素 A 的情况下补充维生素 A 将是有益的，因为这可能是改善妊娠结局的重要策略。

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引用次数: 0

Shatavarin-IV rescues the Di (2-ethylhexyl) phthalate (DEHP) induced oxidative stress in rat granulosa cells in vitro 沙打旺素-IV能挽救大鼠颗粒细胞在体外由邻苯二甲酸二（2-乙基己基）酯（DEHP）诱导的氧化应激。

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-10-26 DOI: 10.1016/j.reprotox.2024.108737

Vivek Pandey , Alka Sharma , Sonal Tiwari , Yashvant Patel , Jayhind Kumar Chauhan , Safiya Ayesha , Alakh N. Sahu , Rashmi Gupta , Anima Tripathi , Pawan K. Dubey

Studies provide notable evidence that oxidative stress (OS) mediated reactive oxygen species (ROS) disturb reproductive health. We have shown in our previous publication that exposure of Di-(2-ethylhexyl) phthalate (DEHP), induces OS mediated ROS generation which inhibits steroid synthesis. In the present study, we demonstrated the ameliorative/protective effects of one of the steroidal saponins, i.e., Shatavarin-IV, isolated from the roots of Asparagus racemosus against DEHP induced OS in rat granulosa cells. Granulosa cells were exposed with DEHP alone (400 μM), Shatavarin-IV alone (8 μg/ml), and a combination of DEHP + Shatavarin-IV (400 μM + 8 μg/ml) in vitro for 24 hrs. Intracellular ROS, OS/hypoxia, mitochondrial membrane potential, steroid-responsive genes expression were analyzed. The results revealed that the effective dose of DEHP (400 µg) significantly increased OS compared to the control by increasing ROS levels, mitochondrial membrane potential, and β-galactosidase activity with a higher level of apoptotic genes (Bax, Caspase-3) expression at mRNA level. Further, DEHP significantly (p < 0.05) reduced mRNA expression of steroidogenic responsive genes (StAR, CYP17A1, and CYP19A1) in granulosa cells treated with above combination compared to control. Interestingly, co-treatment of DEHP + Shatavarin-IV significantly suppressed the DEHP induced OS, ROS, β-galactosidase levels and enhanced steroidogeneic and apoptotic gene expression activities, which suggests that Shatavarin-IV rescued DEHP-induced changes that may useful for the prevention of DEHP- induced reproductive toxicity.

研究表明，氧化应激（OS）介导的活性氧（ROS）会干扰生殖健康。我们在之前发表的文章中指出，接触邻苯二甲酸二（2-乙基己基）酯（DEHP）会诱发 OS 介导的 ROS 生成，从而抑制类固醇的合成。在本研究中，我们证明了从天门冬根中分离出的一种甾体皂甙（即 Shatavarin-IV）对 DEHP 诱导的大鼠颗粒细胞 OS 的改善/保护作用。大鼠颗粒细胞分别与单独的 DEHP（400μM）、单独的 Shatavarin-IV（8μg/ml）和 DEHP + Shatavarin-IV 组合（400μM + 8μg/ml）体外接触 24 小时。对细胞内 ROS、OS/缺氧、线粒体膜电位、类固醇反应基因的表达进行了分析。结果表明，与对照组相比，有效剂量的 DEHP（400µg）可通过增加 ROS 水平、线粒体膜电位和 β-半乳糖苷酶活性显著增加 OS，并在 mRNA 水平上增加凋亡基因（Bax、Caspase-3）的表达。此外，DEHP 能明显（p

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引用次数: 0

Exploring genetic causal relationship between antidepressants use and congenital malformations 探索使用抗抑郁药与先天畸形之间的遗传因果关系。

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-10-18 DOI: 10.1016/j.reprotox.2024.108736

Kaiyan Yang , Xinyu Qin , Huiyan Wang , Wenbo Zhou

Existing studies have demonstrated that the use of antidepressants is associated with congenital malformations; however, the conclusions are inconsistent, and the potential causal relationship remains unclear. Based on large-scale genetic data, we conducted a two-sample Mendelian randomization (MR) study. The exposure datasets included the use of antidepressants, responses to selective serotonin reuptake inhibitors (SSRIs), and the use of four SSRIs-related antidepressants: fluoxetine, citalopram, paroxetine, and sertraline. The outcome datasets encompassed congenital malformations across 12 major organ systems, as well as overall congenital malformations. All datasets were of European ancestry. We employed inverse variance weighting (IVW), MR-Egger, and weighted median methods as our MR analytical approaches. Additionally, the robustness of the MR results was evaluated through a series of sensitivity analyses. After Bonferroni multiple comparisons, MR results did not reveal a significant association between the use of all antidepressants and any congenital malformations. However, IVW provided a suggestive positive association between antidepressants use and congenital digestive malformations (OR = 1.28, 95 % CI = 1.01–1.62, P = 0.039), as well as between SSRIs response and respiratory system malformations (OR = 1.21, 95 % CI = 1.02–1.44, P = 0.033), and fluoxetine use and nervous system malformations (P = 0.026). This study did not find evidence of an association between the use of citalopram, paroxetine, or sertraline and any congenital malformations. Our study provides evidence of a causal association between exposure to antidepressants and certain specific congenital malformations. However, further in-depth research is needed to confirm this association and explore the underlying biological mechanisms.

现有研究表明，使用抗抑郁药与先天性畸形有关，但结论并不一致，潜在的因果关系仍不清楚。基于大规模遗传数据，我们开展了一项双样本孟德尔随机化（MR）研究。暴露数据集包括抗抑郁药的使用情况、对选择性血清素再摄取抑制剂（SSRIs）的反应，以及四种与 SSRIs 相关的抗抑郁药：氟西汀、西酞普兰、帕罗西汀和舍曲林的使用情况。结果数据集包括 12 个主要器官系统的先天性畸形以及总体先天性畸形。所有数据集均为欧洲血统。我们采用了反方差加权法（IVW）、MR-Egger 法和加权中位数法作为 MR 分析方法。此外，我们还通过一系列敏感性分析评估了 MR 结果的稳健性。经过Bonferroni多重比较后，MR结果并未显示使用所有抗抑郁药与任何先天性畸形之间存在显著关联。然而，IVW提供了使用抗抑郁药与先天性消化系统畸形（OR = 1.28，95% CI = 1.01-1.62，P = 0.039）、SSRIs反应与呼吸系统畸形（OR = 1.21，95% CI = 1.02-1.44，P = 0.033）以及使用氟西汀与神经系统畸形（P = 0.026）之间的提示性正相关。本研究未发现使用西酞普兰、帕罗西汀或舍曲林与任何先天性畸形之间存在关联的证据。我们的研究提供了证据，证明接触抗抑郁药与某些特定的先天畸形之间存在因果关系。然而，还需要进一步深入研究，以确认这种关联并探索其背后的生物学机制。

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引用次数: 0

Chlorpyrifos and dimethoate exposure impairs female fertility by deregulating WNT signaling pathway & uterine receptivity 暴露于毒死蜱和乐果会降低 WNT 信号通路和子宫的接受能力，从而损害女性的生育能力。

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-10-16 DOI: 10.1016/j.reprotox.2024.108735

Jasmeena Jan , Showkeen Muzamil Bashir , Wajid Mohammad Sheikh , Owais Mohmad Bhat , Towseef Amin Rafeeqi , Showkat Ahmad Shah , Abid Hamid Dar , Mohammad Afzal Zargar , Nissar Ahmad Wani

The study assessed histological, biochemical, oxidative stress, and molecular parameters to evaluate the consequences of Chlorpyrifos and Dimethoate exposure on uterine health in female rats. Despite showing no obvious signs of toxicity apart from minor clinical symptoms in DM-exposed rats, both pesticides caused degenerative changes in uterine tissue. This study demonstrates that pesticides induce inflammatory responses and oxidative stress in rats, by NF-κB activation and altering antioxidant enzyme levels. Besides, CPF and DM exposure disrupted gene expression of HOXA10, HOXA11, and WNT and reduced activation of β-catenin in the uterus, which is crucial for implantation and reproductive function. These findings suggest that pesticide exposure may impair reproductive health and fertility in females, highlighting potential implications for human health.

该研究评估了组织学、生化、氧化应激和分子参数，以评价接触毒死蜱和乐果对雌性大鼠子宫健康的影响。尽管暴露于这两种杀虫剂的大鼠除了轻微的临床症状外没有明显的中毒症状，但这两种杀虫剂会导致子宫组织发生退行性变化。这项研究表明，杀虫剂通过激活 NF-κB 和改变抗氧化酶水平，诱发大鼠的炎症反应和氧化应激。此外，CPF 和 DM 的暴露破坏了子宫中 HOXA10、HOXA11 和 WNT 的基因表达，并降低了β-catenin 的活化，而β-catenin 对着床和生殖功能至关重要。这些发现表明，接触杀虫剂可能会损害女性的生殖健康和生育能力，对人类健康具有潜在影响。

引用次数: 0