Reproductive toxicology最新文献_第9页

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

Investigating the effects of COVID-19 on sperm in male smokers: A prospective integrated proteomic and metabolomic study 调查 COVID-19 对男性吸烟者精子的影响：前瞻性蛋白质组和代谢组综合研究

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-10-13 DOI: 10.1016/j.reprotox.2024.108734

ChengLu Wang , JiaCheng Zhang , Fang Gao , Min Zheng , XiaoHua Fu , KeBing Yang

Notable variations in semen parameters among non-smoking males have been documented post-COVID-19 pandemic. The role of smoking as a significant contributing factor to male infertility has been substantiated. Does the combined effect of smoking and SARS-CoV-2 infection impact male reproductive function? A prospective descriptive cohort study was performed using data from 90 smoking and 90 non-smoking males before and after coronavirus infection in a single center over a period of 3 months. Semen samples were collected before and within 15 days after COVID-19 infection, ensuring no more than three months elapsed between the two collections. The semen parameters evaluated included volume, concentration, progressive motility, normal morphology, and DNA fragmentation rate. Proteomic and metabolomic studies were further used to explore the differences between groups. Both non-smokers and smokers exhibited a marked reduction in sperm concentration, progressive motility, and normal morphology rate. Additionally, an increase in sperm DNA fragmentation index was noted for non-smokers and smokers. In the non-smoking group, dysregulation proteins including SEMG1, SEMG2 and DNAH5, and metabolites including L-glutamine, cis-9-Palmitoleic acid and Linoleamide were observed. In smokers, dysregulation proteins including SMCP, ROPN1B and IZUMO4, alongside metabolites including carnitine, gamma-Glutamylglutamic acid, and hypoxanthine were found. Comparative analysis between smoking and non-smoking patients post-COVID-19 also revealed significant differences in semen concentration, morphology and sperm DNA fragmentation rate. Dysregulated proteins including HSPA5, HSPA2 and PGK2, and metabolites such as acetylcarnitine, oxaloacetate and nicotinate were associated with impaired sperm function. Our study demonstrates that the virus also significantly compromises sperm quality in smoking males, who experience more pronounced declines post-infection compared to their non-smoking counterparts. This research underscores the necessity for comprehensive fertility assessments for smoking males after recovering from COVID-19.

据记录，COVID-19 大流行后，不吸烟男性的精液参数出现了明显的变化。吸烟是导致男性不育的一个重要因素已得到证实。吸烟和 SARS-CoV-2 感染共同作用是否会影响男性生殖功能？一项前瞻性描述性队列研究使用了一个中心的 90 名吸烟男性和 90 名非吸烟男性在冠状病毒感染前后 3 个月内的数据。在感染 COVID-19 之前和之后的 15 天内采集精液样本，确保两次采集间隔不超过三个月。评估的精液参数包括精液量、精液浓度、精子活力、正常形态和DNA碎片率。蛋白质组学和代谢组学研究进一步用于探究组间差异。非吸烟者和吸烟者的精子浓度、活动力和正常形态率都明显下降。此外，非吸烟者和吸烟者的精子 DNA 碎片指数都有所增加。在非吸烟组中，观察到包括 SEMG1、SEMG2 和 DNAH5 在内的蛋白质以及包括 L-谷氨酰胺、顺式-9-棕榈油酸和亚油酰胺在内的代谢物失调。在吸烟者中，发现了包括 SMCP、ROPN1B 和 IZUMO4 在内的失调蛋白，以及包括肉碱、γ-谷氨酰谷氨酸和次黄嘌呤在内的代谢物。对COVID-19后吸烟和不吸烟患者的比较分析还显示，精液浓度、形态和精子DNA碎片率存在显著差异。HSPA5、HSPA2 和 PGK2 等失调蛋白以及乙酰肉碱、草酰乙酸和烟酸等代谢物与精子功能受损有关。我们的研究表明，病毒也会严重损害吸烟男性的精子质量，与不吸烟的男性相比，吸烟男性的精子质量在感染病毒后会出现更明显的下降。这项研究强调了对 COVID-19 病毒康复后的吸烟男性进行全面生育能力评估的必要性。

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引用次数: 0

AKT/mTOR-mediated autophagic signaling is associated with TCDD-induced cleft palate AKT/mTOR介导的自噬信号与TCDD诱发的腭裂有关。

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-10-12 DOI: 10.1016/j.reprotox.2024.108731

Yaxin Zhang , Dongliang Xu , Shuaixing Song , Guoxu Wang , Hexin Su , Yang Wu , Yuwei Zhang , Hongyan Liu , Qingfu Li , Xiangdong Wang , Zengli Yu , Xiaozhuan Liu

In utero exposure to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can contribute to high rates of cleft palate (CP) formation, but the mechanistic basis for these effects remains uncertain. Here, multi-omics-based metabolomic and transcriptomic analyses were employed to characterize the etiological basis for TCDD-induced CP on gestational day 14.5 (GD14.5). These analyses revealed that TCDD-induced CP formation is associated with calcium, MAPK, PI3K-Akt, and mTOR pathway signaling. PI3K-Akt and mTOR signaling activity is closely linked with the maintenance of cellular proliferation and survival. Moreover, mTOR-mediated regulation of autophagic activity is essential for ensuring an appropriate balance between metabolic activity and growth. Murine embryonic palatal mesenchymal (MEPM) cell proliferation was thus characterized, autophagic activity in these cells was evaluated through electron microscopy and western immunoblotting was used to compare the levels of autophagy- and AKT/mTOR-related protein between the control and TCDD groups on GD14.5. These analyses indicated that MEPM cell proliferative and autophagic activity was inhibited in response to TCDD exposure with the concomitant activation of AKT/mTOR signaling, in line with the multi-omics data. Together, these findings suggested that following TCDD exposure, the activation of AKT/mTOR-related autophagic signaling may play a role in the loss of appropriate palatal cell homeostasis, culminating in the incidence of CP.

子宫内暴露于环境污染物 2,3,7,8-四氯二苯并-对-二恶英（TCDD）会导致腭裂（CP）的高发病率，但这些影响的机理基础仍不确定。在此，研究人员采用了基于多组学的代谢组学和转录组学分析，以确定妊娠14.5天（GD14.5）时TCDD诱发CP的病因学基础。这些分析表明，TCDD诱导的CP形成与钙、MAPK、PI3K-Akt和mTOR通路信号转导有关。PI3K-Akt 和 mTOR 信号活动与维持细胞增殖和存活密切相关。此外，mTOR 介导的自噬活动调节对于确保新陈代谢活动和生长之间的适当平衡至关重要。因此，我们研究了小鼠胚胎腭间质（MEPM）细胞增殖的特征，通过电子显微镜评估了这些细胞的自噬活性，并使用 Western 免疫印迹法比较了对照组和 TCDD 组 GD14.5 自噬和 AKT/mTOR 相关蛋白的水平。这些分析表明，暴露于 TCDD 后，MEPM 细胞的增殖和自噬活性受到抑制，同时 AKT/mTOR 信号也被激活，这与多组学数据一致。这些研究结果表明，暴露于 TCDD 后，AKT/mTOR 相关自噬信号的激活可能会导致适当的腭细胞平衡丧失，最终导致 CP 的发生。

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引用次数: 0

Phthalate monoesters affect membrane fluidity and cell-cell contacts in endometrial stromal adherent cell lines and spheroids 邻苯二甲酸单酯会影响子宫内膜基质粘附细胞系和球状细胞的膜流动性和细胞间接触

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-10-11 DOI: 10.1016/j.reprotox.2024.108733

Darja Lavogina , Keiu Kask , Sergei Kopanchuk , Nadja Visser , Mary Laws , Jodi A. Flaws , Theodora Kunovac Kallak , Matts Olovsson , Pauliina Damdimopoulou , Andres Salumets

Phthalate monoesters have been identified as endocrine disruptors in a variety of models, yet understanding of their exact mechanisms of action and molecular targets in cells remains incomplete. Here, we set to determine whether epidemiologically relevant mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) can affect biological processes by altering cell plasma membrane fluidity or formation of cell-cell contacts. As a model system, we chose endometrial stromal cell lines, one of which was previously used in a transcriptomic study with MEHHP or MEHHP-containing mixtures. A short-term exposure (1 h) of membrane preparations to endocrine disruptors was sufficient to induce changes in membrane fluidity/rigidity, whereas different mixtures showed different effects at various depths of the bilayer. A longer exposure (96 h) affected the ability of cells to form spheroids and highlighted issues with membrane integrity in loosely assembled spheroids. Finally, in spheroids assembled from T-HESC cells, MEHHP interfered with the formation of cell-cell contacts as indicated by the immunostaining of zonula occludens 1 protein. Overall, this study emphasized the need to consider plasma membrane, membrane-bound organelles, and secretory vesicles as possible biological targets of endocrine disruptors and offered an explanation for a multitude of endocrine disruptor roles documented earlier.

邻苯二甲酸酯单酯已被确定为多种模型中的内分泌干扰物，但人们对其确切的作用机制和细胞中的分子靶点的了解仍不全面。在这里，我们试图确定与流行病相关的邻苯二甲酸单（2-乙基-5-羟基己酯）（MEHHP）是否会通过改变细胞质膜流动性或细胞-细胞接触的形成来影响生物过程。我们选择了子宫内膜基质细胞系作为模型系统，其中一种细胞系曾用于 MEHHP 或含 MEHHP 混合物的转录组研究。膜制备物与内分泌干扰物的短期接触（1 小时）足以引起膜流动性/刚性的变化，而不同的混合物在双分子层的不同深度表现出不同的影响。更长时间的暴露（96 小时）会影响细胞形成球体的能力，并突出了松散组装球体的膜完整性问题。最后，在由T-HESC细胞组装的球体内，MEHHP干扰了细胞-细胞接触的形成，这一点可以通过免疫染色Zonula occludens 1蛋白得到证明。总之，这项研究强调了将质膜、膜结合细胞器和分泌囊泡视为内分泌干扰物可能的生物靶点的必要性，并为之前记录的多种内分泌干扰物作用提供了解释。

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引用次数: 0

Exploring the hypothetical links between environmental pollutants, diet, and the gut-testis axis: The potential role of microbes in male reproductive health 探索环境污染物、饮食和肠道-睾丸轴之间的假设联系：微生物在男性生殖健康中的潜在作用

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-10-10 DOI: 10.1016/j.reprotox.2024.108732

Itishree Dubey , Nandheeswari K , Vigneshwaran G , Gourav Rohilla , Lalruatmawii , Pratik Naxine , Jayapradha P , Mahesh Rachamalla , Sapana Kushwaha

The gut system, commonly referred to as one of the principal organs of the human "superorganism," is a home to trillions of bacteria and serves an essential physiological function in male reproductive failures or infertility. The interaction of the endocrine-immune system and the microbiome facilitates reproduction as a multi-network system. Some recent studies that link gut microbiota to male infertility are questionable. Is the gut-testis axis (GTA) real, and does it affect male infertility? As a result, this review emphasizes the interconnected links between gut health and male reproductive function via changes in gut microbiota. However, a variety of harmful (endocrine disruptors, heavy metals, pollutants, and antibiotics) and favorable (a healthy diet, supplements, and phytoconstituents) elements promote microbiota by causing dysbiosis and symbiosis, respectively, which eventually modify the activities of male reproductive organs and their hormones. The findings of preclinical and clinical studies on the direct and indirect effects of microbiota changes on testicular functions have revealed a viable strategy for exploring the GTA-axis. Although the GTA axis is poorly understood, it may have potential ties to reproductive issues that can be used for therapeutic purposes in the future.

肠道系统通常被称为人类 "超级有机体 "的主要器官之一，是数万亿细菌的家园，在男性生殖系统衰竭或不育症中发挥着重要的生理功能。内分泌-免疫系统和微生物群的相互作用促进了作为多网络系统的生殖。最近一些将肠道微生物群与男性不育联系起来的研究值得商榷。肠道-睾丸轴（GTA）是真实存在的吗？因此，本综述强调通过肠道微生物群的变化，肠道健康与男性生殖功能之间存在相互联系。然而，各种有害元素（内分泌干扰素、重金属、污染物和抗生素）和有利元素（健康饮食、补充剂和植物成分）分别通过引起菌群失调和共生来促进微生物群，最终改变男性生殖器官及其激素的活动。关于微生物群变化对睾丸功能的直接和间接影响的临床前和临床研究结果，揭示了探索 GTA 轴的可行策略。虽然人们对 GTA 轴的了解甚少，但它可能与生殖问题有潜在联系，未来可用于治疗目的。

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引用次数: 0

Trifluoperazine effect on human sperm: The accumulation of reactive oxygen species and the decrease in the mitochondrial membrane potential 三氟拉嗪对人类精子的影响：活性氧积累和线粒体膜电位降低。

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-10-05 DOI: 10.1016/j.reprotox.2024.108730

Houpeng Wang , Cheng Cheng , Jing Ding , Ruirui Qian , Tao Luo , Liping Zheng , Ying Chen

A strong link between antipsychotic drug use and reduced human sperm quality has been reported. Trifluoperazine (TFP), a commonly used antipsychotic, is now being explored for anticancer applications. Although there are hints that TFP might affect the male reproductive system, its impact on human sperm quality remains uncertain. Using a human sperm and TFP in vitro coculture system, we examined the effect of TFP (12.5, 25, 50 and 100 μM) on human sperm function and physiological parameters. The results showed that 50 μM and 100 μM TFP induced the accumulation of reactive oxygen species (ROS) and a decrease in the mitochondrial membrane potential (MMP) of human sperm, leading to decreased sperm viability, while 25 μM TFP inhibited only the penetration ability, total sperm motility, and progressive motility. Although 12.5 μM and 25 μM TFP increased [Ca²⁺]_i in human sperm, they did not affect capacitation or the acrosome reaction. These results may be explained by the observation that 12.5 μM and 25 μM TFP did not increase tyrosine phosphorylation in human sperm, although TFP increased [Ca²⁺]_i in a time-course traces similar to that of progesterone. Our results indicated that TFP could cause male reproductive toxicity by inducing the accumulation of ROS and a decrease in the MMP in human sperm.

据报道，抗精神病药物的使用与人类精子质量下降之间存在密切联系。三氟拉嗪（TFP）是一种常用的抗精神病药物，目前正被用于抗癌研究。虽然有迹象表明三氟拉嗪可能会影响男性生殖系统，但其对人类精子质量的影响仍不确定。我们使用人类精子和 TFP 体外共培养系统，研究了 TFP（12.5、25、50 和 100μM）对人类精子功能和生理参数的影响。结果表明，50μM 和 100μM TFP 会诱导活性氧（ROS）的积累和线粒体膜电位（MMP）的降低，从而导致精子活力下降；而 25μM TFP 只抑制精子的穿透能力、总活力和渐进活力。虽然 12.5μM 和 25μM TFP 会增加人类精子中的[Ca2+]i，但它们并不影响获能和顶体反应。虽然 12.5μM 和 25μM TFP 增加人类精子中[Ca2+]i 的时间历程与黄体酮相似，但它们并没有增加精子中的酪氨酸磷酸化，这可能可以解释上述结果。我们的研究结果表明，全氟辛基磺酰氟可通过诱导 ROS 的积累和人类精子中 MMP 的减少而导致男性生殖毒性。

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