Reproductive toxicology最新文献_第8页

A common phthalate replacement disrupts ovarian function in young adult mice 一种常见的邻苯二甲酸酯替代品会破坏年轻成年小鼠的卵巢功能。

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-11-15 DOI: 10.1016/j.reprotox.2024.108748

Courtney Potts, Allison Harbolic, Maire Murphy, Michelle Jojy, Christine Hanna, Maira Nadeem, Hanin Alahmadi, Stephanie Martinez, Genoa R. Warner

Di-2-ethylhexyl terephthalate (DEHTP) is a replacement for its structural isomer di-2-ethylhexyl phthalate (DEHP), a known endocrine disrupting chemical and ovarian toxicant. DEHTP is used as a plasticizer in polyvinyl chloride products and its metabolites are increasingly found in biomonitoring studies at levels similar to phthalates. However, little is known about the effects of DEHTP on the ovary. In this research, we tested the hypothesis that DEHTP is an ovarian toxicant and likely endocrine disrupting chemical like its isomer DEHP. The impact of environmentally relevant exposure to DEHTP and/or its metabolite mono-2-ethylhexyl terephthalate (MEHTP) on the mouse ovary was investigated in vivo and in vitro. For the in vivo studies, young adult CD-1 mice were orally dosed with vehicle, 10 µg/kg, 100 µg/kg, or 100 mg/kg of DEHTP for 10 days. For the in vitro studies, isolated untreated ovarian follicles were exposed to vehicle, 0.1, 1, 10, or 100 µg/mL of DEHTP or MEHTP. Follicle counts, hormone levels, and gene expression of steroidogenic enzymes, cell cycle regulators, and apoptosis factors were analyzed. In vivo, DEHTP exposure altered follicle counts compared to control. DEHTP exposure also decreased expression of cell cycle regulators and apoptotic factors compared to control. In vitro, follicle growth was reduced compared to controls, and expression of the cell cycle regulator Cdkn2b was increased. Overall, these results suggest that DEHTP and MEHTP may be ovarian toxicants at low doses and should be subjected to further scrutiny for reproductive toxicity due to their similar structures to phthalates.

邻苯二甲酸二-2-乙基己酯（DEHTP）是其结构异构体邻苯二甲酸二-2-乙基己酯（DEHP）的替代品，后者是一种已知的内分泌干扰化学品和卵巢毒物。DEHTP 在聚氯乙烯产品中用作增塑剂，其代谢物在生物监测研究中的含量越来越接近邻苯二甲酸盐。然而，人们对 DEHTP 对卵巢的影响知之甚少。在这项研究中，我们测试了一种假设，即 DEHTP 与它的异构体 DEHP 一样，是一种卵巢毒性物质，而且很可能是一种干扰内分泌的化学物质。我们在体内和体外研究了小鼠暴露于 DEHTP 和/或其代谢物对苯二甲酸单-2-乙基己酯（MEHTP）对卵巢的影响。在体内研究中，年轻的成年 CD-1 小鼠连续 10 天分别口服载体、10µg/kg、100µg/kg 或 100mg/kg DEHTP。在体外研究中，分离出的未经处理的卵巢卵泡暴露于载体、0.1、1、10或100µg/mL的DEHTP或MEHTP。对卵泡数量、激素水平以及类固醇生成酶、细胞周期调节因子和凋亡因子的基因表达进行了分析。在体内，与对照组相比，暴露于 DEHTP 会改变卵泡数量。与对照组相比，暴露于DEHTP还会降低细胞周期调节因子和细胞凋亡因子的表达。在体外，与对照组相比，卵泡生长减少，细胞周期调节因子 Cdkn2b 的表达增加。总之，这些结果表明，DEHTP 和 MEHTP 可能是低剂量的卵巢毒物，由于其结构与邻苯二甲酸盐相似，因此应进一步研究其生殖毒性。

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引用次数: 0

Bisphenol A-induced polycystic ovary syndrome (PCOS) with hormonal and metabolic implications in rats 双酚 A 诱导的多囊卵巢综合征（PCOS）对大鼠荷尔蒙和新陈代谢的影响。

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-11-15 DOI: 10.1016/j.reprotox.2024.108750

Mehjbeen Javed, Suramya, Anuradha Mangla, Garima Jindal, Humaira Naaz Bhutto, Shaesta Shahid, Suraj Kumar, Sheikh Raisuddin

There is a rising incidence of polycystic ovary syndrome (PCOS) cases worldwide in women of reproductive age due to environmental factors. We evaluated the effect of an environmental estrogen, bisphenol A (BPA) for its reprotoxicity regarding the induction of PCOS in rats and also assessed its hormonal and metabolic implications. There was 66.6 % and 50 % disorder, in the estrus cycle at low (50 µg/kg) and high (500 µg/kg) doses of BPA, respectively. While animals treated with the positive control (dehydroepiandrosterone, DHEA at 6 mg/100 g) caused 100 % disorder. Cystic and atretic follicles along with two corpora lutea were found in the low dose group. However, no corpus luteum was found in the high dose group. Furthermore, hyperplasia and hypertrophy were found in the myometrium, endometrium, and luminal epithelium of the uterus of the low dose and DHEA groups. Additionally, 17β estradiol, progesterone, DHEA, androstenedione, testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone sulphate (DHEAS), antimullerian hormone (AMH), ratio of LH/FSH and testosterone/DHT were increased significantly (P < 0.01) in BPA groups. A significantly higher TSH (P < 0.01) indicates hypothyroidism. Furthermore, hyperglycemia, hyperinsulinemia, HOMA-IR, and HOMAβ indicate insulin resistance in the low-dose group. Thus, the low dose of BPA was found to be more potent as compared to the higher dose in defining the hyperandrogenic state. Our study revealed that BPA may not only be a causative factor in the induction of PCOS but also has metabolic implications bearing on its estrogenic nature.

由于环境因素的影响，全球育龄妇女多囊卵巢综合症（PCOS）的发病率不断上升。我们评估了环境雌激素双酚 A 对诱导大鼠多囊卵巢综合征的生殖毒性影响，并评估了其对荷尔蒙和新陈代谢的影响。低剂量（50 微克/千克）和高剂量（500 微克/千克）双酚 A 会导致 66.6% 和 50% 的发情周期紊乱。而用阳性对照（脱氢表雄酮，DHEA，6 毫克/100 克）处理的动物则会导致 100%的发情周期紊乱。在低剂量组中发现了囊性和闭锁卵泡以及两个黄体。但高剂量组未发现黄体。此外，低剂量组和 DHEA 组的子宫肌层、子宫内膜和管腔上皮均出现增生和肥厚。此外，双酚 A 组的 17β 雌二醇、孕酮、DHEA、雄烯二酮、睾酮、双氢睾酮（DHT）、硫酸脱氢表雄酮（DHEAS）、抗苗勒氏激素（AMH）、LH/FSH 和睾酮/DHT 的比率均显著增加（P < 0.01）。TSH 明显升高（P < 0.01）表明甲状腺功能减退。此外，低剂量组的高血糖、高胰岛素血症、HOMA-IR 和 HOMAβ 表明存在胰岛素抵抗。因此，与高剂量相比，低剂量双酚 A 的作用更强，更能确定高雄激素状态。我们的研究表明，双酚 A 不仅可能是诱发多囊卵巢综合症的致病因素，而且其雌激素性质对代谢也有影响。

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引用次数: 0

Selenium ameliorates oxidized phospholipid-mediated testicular dysfunction and epididymal sperm abnormalities following Bisphenol A exposure in adult Wistar rats 硒能改善成年 Wistar 大鼠接触双酚 A 后氧化磷脂介导的睾丸功能障碍和附睾精子异常。

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-11-15 DOI: 10.1016/j.reprotox.2024.108751

Meenu Maniradhan , Narmadhaa Sivagurunathan , Ajay Krishnan Unnikrishnan , Vigil S. Anbiah , Latchoumycandane Calivarathan

Bisphenol A (BPA) is an endocrine-disrupting compound extensively utilized in the production of polycarbonate polymers and epoxy resins that, upon exposure, pose a significant threat to male reproductive health because of its estrogenic properties. Accumulating evidence suggests that BPA exposure disrupts the normal process of spermatogenesis, alters testicular morphology and function, and interferes with testicular steroidogenesis and hormonal signaling. However, the precise mechanism by which BPA affects testicular function remains unclear. In this study, we explored the mechanism underlying BPA-induced testicular abnormalities and evaluated the protective effects of Selenium (Se). Thirty-two adult male albino Wistar rats were divided into four groups, and BPA was administered at 50 mg/kg body weight, with or without Se supplementation, for 30 days. Se supplementation (2.5 mg/kg body weight) was initiated 1 week before BPA administration. BPA administration resulted in alterations in testicular architecture, characterized by basement membrane disintegration in the seminiferous tubules, reduced spermatogenic cell counts, and increased interstitial tubule noncellular space. Furthermore, BPA exposure increased the levels of oxidized phospholipids, lipid peroxides, and hydroxyl radicals and decreased the activities of the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. In addition, BPA significantly reduced the activities of 3β- and 17β-hydroxysteroid dehydrogenases, interfering with testicular steroidogenesis. In rats, coadministration of Se and BPA reduced the levels of oxidized phospholipids and increased the activities of antioxidant enzymes, leading to improved testicular function and epididymal sperm parameters, suggesting that Se plays a critical role in alleviating endocrine disruptor-induced testicular dysfunctions in rats.

双酚 A（BPA）是一种干扰内分泌的化合物，广泛用于生产聚碳酸酯聚合物和环氧树脂。越来越多的证据表明，接触双酚 A 会破坏精子生成的正常过程，改变睾丸的形态和功能，干扰睾丸的类固醇生成和激素信号转导。然而，双酚 A 影响睾丸功能的确切机制仍不清楚。在这项研究中，我们探讨了双酚 A 诱导睾丸异常的机制，并评估了硒（Se）的保护作用。研究人员将 32 只成年雄性白化 Wistar 大鼠分为四组，按每公斤体重 50 毫克的剂量给它们注射双酚 A，并在注射或不注射 Se 的情况下持续 30 天。在服用双酚 A 前一周开始补充 Se（2.5 毫克/千克体重）。服用双酚 A 会导致睾丸结构改变，表现为曲细精管基底膜崩解、生精细胞数量减少以及间质小管非细胞间隙增加。此外，暴露于双酚 A 会增加氧化磷脂、脂质过氧化物和羟基自由基的水平，降低超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和谷胱甘肽还原酶等抗氧化酶的活性。此外，双酚 A 会明显降低 3β- 和 17β- 羟基类固醇脱氢酶的活性，从而干扰睾丸类固醇的生成。在大鼠体内，联合给药 Se 和双酚 A 可降低氧化磷脂的水平，提高抗氧化酶的活性，从而改善睾丸功能和附睾精子参数，这表明 Se 在缓解内分泌干扰物引起的大鼠睾丸功能障碍方面发挥着关键作用。

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引用次数: 0

Investigating the significance of the transgenerational impact of high and repeated doses of ivermectin: Effects on paternal testis histopathology, pups' development, and sexual behavior 研究高剂量和重复剂量伊维菌素对跨代影响的意义：对父代睾丸组织病理学、幼鼠发育和性行为的影响

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-11-08 DOI: 10.1016/j.reprotox.2024.108743

Natalia Moreira , Kassia de Carvalho , Gabriel Aur Borges , Lais Coelho Cortez , Laura de Macedo Amado , Rodrigo Augusto Foganholi da Silva , Flora Cordeiro , Maria Martha Bernardi

Paternal exposure to environmental challenges is critical for the offspring's future health, and the transmission of acquired traits through generations increases the risk of offspring developing diseases. Ivermectin (IVM) is widely used in veterinary and human medicine to treat parasitosis. Our previous studies showed that IVM acute administration induced disorganization of the germinal epithelium and could cause damage to sperm production. Thus, this study investigated the effects of paternal exposure to repeated high ivermectin doses on paternal testis histology. After mating, their pups' development and sexual behavior in adult rats were examined. Method: Two groups of male rats were treated with IVM or its vehicle once a week for three weeks. We observed these males' body weight, organs and testis histology, and testosterone levels. These rats were mated with females without any treatment: the reproductive performance, the offspring development, and the male and female sexual behavior observed in adulthood. Relative to controls, the IVM paternal testis histology showed hypertrophy and hyperplasia of Leydig cells and increased diameter of the seminiferous tubules—no impairment in reproductive performance. In males and females, the physical and reflexes were modified. In adult age, female rats of the IVM group showed reduced sexual behavior and sexual preferences for the same sex, while male sexual behavior was not altered. Thus, it is possible that paternal exposure to IVM interfered with pups' hormonal and growth factors during development and in adult age. Further studies are needed to explore IVM transgenerational effects identifying possible mechanisms underpinning behavioral effects.

父代所面临的环境挑战对子代未来的健康至关重要，后天性状的代代相传会增加子代罹患疾病的风险。伊维菌素（IVM）被广泛应用于兽医和人类医学中治疗寄生虫病。我们之前的研究表明，IVM 急性给药会引起生殖上皮细胞的紊乱，并可能对精子的产生造成损害。因此，本研究调查了父代多次暴露于高剂量伊维菌素对父代睾丸组织学的影响。交配后，对幼鼠的发育和成年大鼠的性行为进行检测。研究方法对两组雄性大鼠进行每周一次的伊维菌素或其载体治疗，为期三周。我们观察了这些雄性大鼠的体重、器官和睾丸组织学以及睾酮水平。这些雄性大鼠在未经任何处理的情况下与雌性大鼠交配：观察其成年后的生殖表现、后代发育以及雌雄性行为。与对照组相比，IVM 大鼠父系睾丸组织学显示，Leydig 细胞肥大和增生，曲细精管直径增大，但生殖能力未受影响。雄性和雌性大鼠的体能和反射均有所改变。成年后，IVM 组雌性大鼠的性行为和对同性的性偏好减少，而雄性大鼠的性行为没有改变。因此，父亲接触 IVM 可能会干扰幼鼠在发育期间和成年后的荷尔蒙和生长因子。还需要进一步研究 IVM 的跨代效应，以确定行为效应的可能机制。

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引用次数: 0

Alcohol induces p53-mediated apoptosis in neural crest by stimulating an AMPK-mediated suppression of TORC1, S6K, and ribosomal biogenesis 酒精通过刺激 AMPK 介导的对 TORC1、S6K 和核糖体生物生成的抑制，诱导 p53 介导的神经嵴凋亡。

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2024-11-07 DOI: 10.1016/j.reprotox.2024.108747

Yanping Huang , George R. Flentke , Susan M. Smith

Prenatal alcohol exposure is a leading cause of permanent neurodevelopmental disability and can feature distinctive craniofacial deficits that partly originate from the apoptotic deletion of craniofacial progenitors, a stem cell lineage called the neural crest (NC). We recently demonstrated that alcohol causes nucleolar stress in NC through its suppression of ribosome biogenesis (RBG) and this suppression is causative in their p53/MDM2-mediated apoptosis. Here, we show that this nucleolar stress originates from alcohol’s activation of AMPK, which suppresses TORC1 and the p70/S6K-mediated stimulation of RBG. Alcohol-exposed cells of the pluripotent, primary cranial NC line O9–1 were evaluated with respect to their S6K, TORC1, and AMPK activity. The functional impact of these signals with respect to RBG, p53, and apoptosis were assessed using gain-of-function constructs and small molecule mediators. Alcohol rapidly (<2 hr) increased pAMPK, pTSC2, and pRaptor, and reduced both total and pS6K in NC cells. These changes persisted for at least 12 hr to 18 hr following alcohol exposure. Attenuation of these signals via gain- or loss-of-function approaches that targeted AMPK, S6K, or TORC1 prevented alcohol’s suppression of rRNA synthesis and the induction of p53-stimulated apoptosis. We conclude that alcohol induces ribosome dysbiogenesis and activates their p53/MDM2-mediated apoptosis via its activation of pAMPK, which in turn activates TSC2 and Raptor to suppress the TORC1/S6K-mediated promotion of ribosome biogenesis. This represents a novel mechanism underlying alcohol’s neurotoxicity and is consistent with findings that TORC1/S6K networks are critical for cranial NC survival.

产前酒精暴露是导致永久性神经发育障碍的主要原因之一，并可能导致独特的颅面缺陷，其部分原因是颅面祖细胞（一种称为神经嵴（NC）的干细胞系）的凋亡性缺失。我们最近证明，酒精通过抑制核糖体生物生成（RBG）导致NC细胞核极应激，而这种抑制是p53/MDM2介导的细胞凋亡的原因。在这里，我们发现这种核极应激源于酒精对 AMPK 的激活，AMPK 可抑制 TORC1 和 p70/S6K 介导的 RBG 刺激。研究人员评估了暴露于酒精的多能原代头颅NC细胞系O9-1细胞的S6K、TORC1和AMPK活性。利用功能增益构建物和小分子介导物评估了这些信号对 RBG、p53 和细胞凋亡的功能影响。酒精能迅速(

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引用次数: 0

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