Reproductive toxicology最新文献_第5页

Guarding the ovarian reserve: Maternal methyl donor supplementation protects against propylparaben-induced ovarian aging in offspring 保护卵巢储备：母体甲基供体补充可防止对羟基苯甲酸丙酯诱导的后代卵巢衰老。

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2026-03-01 Epub Date: 2026-01-11 DOI: 10.1016/j.reprotox.2026.109167

Yaling Wu , Yi Chen , Shixuan Wang , Tong Wu , Jinjin Zhang

Prenatal exposure to endocrine-disrupting chemicals is increasingly recognized as a contributing factor to female reproductive aging. Propylparaben (PRP), a widely used preservative with estrogenic activity, is ubiquitously detected in human biological samples, raising concern regarding gestational exposure. However, how prenatal PRP exposure affects ovarian development and whether nutritional interventions confer protection remain unclear. Here, pregnant mice were exposed to PRP from embryonic day 7.5 to E13.5, with or without maternal methyl donor (MD) supplementation. Prenatal PRP exposure was associated with impaired primordial follicle pool establishment as early as postnatal day 7 and reduced ovarian reserve and fertility in adult offspring. These effects were associated with increased oxidative stress, inflammation, fibrotic remodeling, hyperactivation of PI3K/AKT/mTOR signaling, and aberrant DNA methylation, collectively contributing to premature follicle activation and depletion. Maternal MD supplementation partially mitigated PRP-induced ovarian injury, helped preserve follicle homeostasis, and improved reproductive outcomes, accompanied by partial restoration of DNA methylation and moderation of aberrant pathway activation. These findings suggest that maternal MD intake may offer a potential nutritional approach to mitigating long-term reproductive risks associated with prenatal PRP exposure.

产前接触干扰内分泌的化学物质越来越被认为是导致女性生殖老化的一个因素。对羟基苯甲酸丙酯（PRP）是一种广泛使用的具有雌激素活性的防腐剂，在人类生物样本中普遍存在，引起了人们对妊娠暴露的关注。然而，产前PRP暴露如何影响卵巢发育以及营养干预是否具有保护作用仍不清楚。在这里，怀孕小鼠从胚胎第7.5天到第13.5天暴露于PRP，添加或不添加母体甲基供体（MD）。产前PRP暴露与早在出生后第7天的原始卵泡池建立受损以及成年后代卵巢储备和生育能力降低有关。这些影响与氧化应激、炎症、纤维化重塑、PI3K/AKT/mTOR信号的过度激活以及异常的DNA甲基化有关，共同导致了早卵泡的激活和消耗。母体补充MD部分减轻了prp诱导的卵巢损伤，有助于保持卵泡稳态，改善生殖结果，同时部分恢复DNA甲基化和调节异常途径激活。这些发现表明，孕妇摄入MD可能提供一种潜在的营养途径，以减轻与产前PRP暴露相关的长期生殖风险。

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引用次数: 0

A mouse model of busulfan-induced ovarian toxicity and evidence for attenuation with mTOR inhibition 布苏芬诱导的小鼠卵巢毒性模型及mTOR抑制减弱的证据。

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2026-03-01 Epub Date: 2025-12-27 DOI: 10.1016/j.reprotox.2025.109153

Mari Deguchi, Yuji Tanaka, Akiko Nakamura, Tsukuru Amano, Ayako Inatomi, Hiroyuki Yamanaka, Akimasa Takahashi, Tetsuro Hanada, Yutaka Yoneoka, Shunichiro Tsuji

Busulfan, an alkylating agent used in hematopoietic stem cell transplantation conditioning, is associated with a high risk of ovarian toxicity. We established a time-resolved in vivo model of busulfan-induced ovarian injury and tested whether sapanisertib, an mTOR inhibitor, mitigates damage. Mice received busulfan (30 mg/kg, intraperitoneally) or saline; ovaries were assessed at 12, 24, and 72 h and 7 days by hematoxylin and eosin histology, follicle counting, TUNEL, and Ki-67 immunohistochemistry. A separate cohort received daily oral sapanisertib (0.3 mg/kg) from 7 days before busulfan through euthanasia; proliferation was assessed at 24 h, and follicle counts at 7 days. In the busulfan-only group, Ki-67 staining showed an early proliferative surge at 24 h in growing follicles, including primary follicles, whereas loss of primordial follicles and an increased primary-to-primordial follicle ratio were evident by 7 days. Primordial follicles showed no TUNEL-positive cells through 72 h, whereas growing follicles were frequently TUNEL-positive. Relative to busulfan alone, the mTOR inhibitor preserved primordial follicles, shifted the primary-to-primordial ratio toward control values, and reduced the proportion of primary follicles with extensive proliferation at 24 h. These findings are consistent with premature activation of primordial follicles as a proximate contributor to busulfan-induced loss of ovarian reserve and suggest that mTOR inhibition may mitigate this process. A two-time-point assay (24 h for proliferation, 7 days for morphology) provides a practical framework for future studies and translation.

Busulfan是一种用于造血干细胞移植调理的烷基化剂，与卵巢毒性的高风险相关。我们建立了一个时间分辨的布苏芬诱导卵巢损伤的体内模型，并测试了sapanisertib（一种mTOR抑制剂）是否能减轻损伤。小鼠腹腔注射丁硫丹（30mg/kg，腹腔注射）或生理盐水；在12、24、72小时和7天通过苏木精和伊红组织学、卵泡计数、TUNEL和Ki-67免疫组织化学对卵巢进行评估。另一个队列从布苏凡前7天开始每天口服萨巴尼替布（0.3mg/kg）直至安乐死；24小时观察细胞增殖，7天观察卵泡计数。在单药组中，Ki-67染色显示生长中的卵泡（包括原发卵泡）在24小时内早期增殖激增，而在7天内，原始卵泡的损失和原发与原始卵泡的比例明显增加。原始卵泡在72小时内未显示tunel阳性细胞，而生长卵泡则经常显示tunel阳性。相对于单独使用busulfan， mTOR抑制剂保存了原始卵泡，将原始与原始的比例转向控制值，并在24小时内降低了广泛增殖的原始卵泡的比例。这些发现与原始卵泡的过早激活是busulfan诱导的卵巢储备丧失的近似因素相一致，并表明mTOR抑制可能减轻这一过程。两个时间点实验（增殖24小时，形态7天）为未来的研究和翻译提供了实用的框架。

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引用次数: 0

Hypothesis-driven approach to developmental toxicity assessment: Using mechanistic information to inform testing 假设驱动的发育毒性评估方法：利用机制信息为测试提供信息。

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2026-03-01 Epub Date: 2025-11-29 DOI: 10.1016/j.reprotox.2025.109119

George Daston , Matthew Burbank , Florian Gautier , Barbara F. Hales , Amer Jamalpoor , Yasunari Kanda , Susan Makris , Aldert H. Piersma , Nicola Powles-Glover , Sonya Sobrian , Vicki Sutherland , Steven Van Cruchten , Ronald L. Wange , Connie L. Chen

Developmental toxicity assessment relies on standardized guideline protocols in which animals (usually rats and/or rabbits) are exposed to the test(s) agent(s) and pregnancy outcomes are assessed at an organismal level. Increasing information about mechanisms of toxicity now allows improved selection of in vivo and in vitro models for assessing developmental toxicity and prediction of developmental outcome by investigating the mode of action (MoA) of the test agent, allowing for a more flexible resource-efficient approach. Read-across, already widely used for chemical assessment, relies on a combination of cheminformatics to select suitable analogs and any of a variety of methods to prove biological similarity and/or a common metabolic pathway. Some of these methods include high-throughput test batteries (e.g., ToxCast) and transcriptomics linked to large databases of gene expression profiles. These can be used to both generate and test hypotheses about MoA of novel compounds. Increasing availability of induced pluripotent stem cells provides greater range of biological models that closely mimic the human biology relevant for addressing a specific hypothesis. Examples are given of how (1) understanding mode of action can be used to identify activity cliffs in a series of analogous chemicals, (2) the use of metabolism data in an example demonstrating that closely related analogs do not all have to be tested in developmental toxicity protocols, and (3) how analysis of gene expression can be used to identify divergent pharmacology in similar chemicals. It is possible using the approaches described to design more flexible, hypothesis-driven approaches to assess developmental toxicity.

发育毒性评估依赖于标准化的指导方案，其中动物（通常是大鼠和/或兔子）暴露于试验剂，并在机体水平上评估妊娠结局。关于毒性机制的信息越来越多，现在可以通过研究试验剂的作用模式（MoA）来改进体内和体外模型的选择，以评估发育毒性和预测发育结果，从而实现更灵活的资源效率方法。Read-across已经广泛用于化学评估，它依赖于化学信息学的结合来选择合适的类似物和各种方法中的任何一种来证明生物相似性和/或共同的代谢途径。其中一些方法包括高通量测试电池（例如ToxCast）和与大型基因表达谱数据库相关联的转录组学。这些可以用来产生和测试关于新化合物的MoA的假设。越来越多的诱导多能干细胞提供了更大范围的生物学模型，这些模型与解决特定假设的人类生物学密切相关。举例说明如何(1)了解作用模式可用于识别一系列类似化学物质中的活性悬崖，(2)在一个例子中使用代谢数据证明密切相关的类似物并不都必须在发育毒性方案中进行测试，以及(3)如何使用基因表达分析来识别类似化学物质中的不同药理学。有可能使用所描述的方法来设计更灵活的、假设驱动的方法来评估发育毒性。

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引用次数: 0

Atrazine and diazinon inhibit oocyte maturation and ovulation in zebrafish 阿特拉津和二嗪醌抑制斑马鱼卵母细胞成熟和排卵。

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2026-03-01 Epub Date: 2026-01-22 DOI: 10.1016/j.reprotox.2026.109172

Md Hasan Ali , Maisum Sarwar Jyoti , Mrityunjoy Acharjee , Shakhawat Hossain , Saokat Ahamed , Md. Forhad Hossain , Toshinobu Tokumoto

Oocyte maturation and ovulation are well characterized biological processes in fish that are induced by progestins through the coordination of nongenomic actions via the membrane progesterone receptor (mPR) and genomic actions via the nuclear progesterone receptor (Pgr). In zebrafish, the effects of chemicals on these processes can be elucidated using in vitro and in vivo oocyte maturation and ovulation assays. The binding affinity of chemicals for mPR and Pgr can be analyzed using a recently established graphene quantum dot (GQD)-labeled mPR and Pgr binding assay. Combining these physiological and biochemical analyses makes it possible to investigate whether the effects of chemical substances on oocyte maturation and ovulation are mediated by mPR and Pgr. In this study, the effects of herbicides and pesticides on fish oocyte maturation and ovulation were evaluated using in vitro and in vivo assays. The findings revealed that at concentrations greater than 0.1 μM, atrazine (ATZ) and diazinon (DZN) substantially reduced oocyte maturation, whereas 2,4-D exposure did not have a similar effect. ATZ and DZN reduced oocyte maturation and ovulation in vivo. However, the concentrations of these compounds required to inhibit ovulation were significantly lower than those required to inhibit oocyte maturation. The binding affinity of endocrine-disrupting chemicals (EDCs) was analyzed using GQD-labeled mPR and Pgr binding assays. All three EDCs—ATZ, DZN, and 2,4-D—exhibited binding affinity for mPR. For Pgr, DZN and 2,4-D exhibited binding affinity, but ATZ did not. These results suggest that ATZ and DZN prevent fish oocyte maturation and ovulation by binding to mPR.

卵母细胞成熟和排卵是由孕激素通过膜孕激素受体（mPR）和核孕激素受体（Pgr）的非基因组作用协调诱导的鱼类生物过程。在斑马鱼中，化学物质对这些过程的影响可以通过体外和体内卵母细胞成熟和排卵试验来阐明。化学物质对mPR和Pgr的结合亲和力可以使用最近建立的石墨烯量子点（GQD）标记的mPR和Pgr结合实验来分析。结合这些生理生化分析，可以探讨化学物质对卵母细胞成熟和排卵的影响是否由mPR和Pgr介导。本研究通过体外和体内实验，评价了除草剂和农药对鱼类卵母细胞成熟和排卵的影响。结果表明，在浓度大于0.1μM时，阿特拉津（ATZ）和二嗪醌（DZN）显著降低卵母细胞成熟，而2,4- d暴露没有类似的影响。ATZ和DZN在体内降低卵母细胞成熟和排卵。然而，抑制排卵所需的这些化合物的浓度明显低于抑制卵母细胞成熟所需的浓度。使用gqd标记的mPR和Pgr结合试验分析内分泌干扰化学物质（EDCs）的结合亲和力。所有三种EDCs-ATZ、DZN和2,4- d都表现出与mPR的结合亲和力。对于Pgr， DZN和2,4- d具有结合亲和力，而ATZ没有。这些结果表明，ATZ和DZN通过与mPR结合来阻止鱼卵母细胞成熟和排卵。

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引用次数: 0

Development of canine testicular organoid for assessing the effects of environmental exposure 用于评估环境暴露影响的犬睾丸类器官的开发。

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2026-03-01 Epub Date: 2025-11-27 DOI: 10.1016/j.reprotox.2025.109117

Lei Yin , Zoey Hsuan Hsiao , Chelin Hu , Xiaozhong (John) Yu

Modeling the male reproductive system in vitro remains challenging due to its complex structure and function such as spermatogenesis. To enhance translational relevance and adhere to the 3 R principles -Replacement, Reduction, Refinement, we developed a three-dimensional (3D) canine testicular organoid model using testes ethically obtained from routine neutering procedures. Testicular cells were isolated via enzymatic digestion, seeded into agarose micro-molds, embedded in extracellular matrix, and cultured for up to 21 days. Organoids increased in diameter (500–1072 μm) and developed complex branching morphologies. Immunofluorescence confirmed the presence of key testicular cell types, including germ cells (GCNA1), Sertoli cells (SOX9), and Leydig cells (HSD3B1), as well as germ cell populations expressing stage-specific differentiation markers, SALL4, DPPA3, PRMT7, and SCP3. Temporal gene expression analysis revealed dynamic regulation of markers involved in testicular function and spermatogenesis, including significant upregulation of GATA4. To evaluate toxicological responsiveness, organoids were exposed to cadmium chloride (CdCl₂). Treatment with 1 μM CdCl₂ significantly reduced cell viability, and 5 μM exposure induced γ-H2AX expression, indicating DNA damage and cellular stress. These findings demonstrate the successful generation and functional validation of a canine testicular organoid model that supports germ cell maintenance and enables mechanistic assessment of reproductive toxicants. This system represents a scientifically robust and ethically sourced alternative to traditional in vivo approaches for evaluating male reproductive toxicity.

由于其复杂的结构和功能（如精子发生），男性生殖系统的体外建模仍然具有挑战性。为了提高翻译的相关性，并坚持3R原则-替换，减少，细化，我们开发了一个三维（3D）犬睾丸类器官模型，使用从常规绝育手术中获得的睾丸。通过酶解分离睾丸细胞，将其植入琼脂糖微霉菌中，包埋在细胞外基质中，培养21天。类器官直径增大（500 ~ 1072 μm），分支形态复杂。免疫荧光证实了关键睾丸细胞类型的存在，包括生殖细胞（GCNA1）、支持细胞（SOX9）和间质细胞（HSD3B1），以及表达阶段特异性分化标记物SALL4、DPPA3、PRMT7和SCP3的生殖细胞群。时间基因表达分析揭示了睾丸功能和精子发生相关标记的动态调控，包括GATA4的显著上调。为了评估毒性反应，类器官暴露于氯化镉（CdCl₂）。1μM CdCl 2处理显著降低细胞活力，5μM暴露诱导γ-H2AX表达，表明DNA损伤和细胞应激。这些发现证明了犬睾丸类器官模型的成功生成和功能验证，该模型支持生殖细胞维持并能够对生殖毒物进行机制评估。该系统代表了一种科学可靠和道德来源的替代传统的体内方法来评估男性生殖毒性。

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引用次数: 0

CORRIGENDUM, Long Term Exposure to Benzo[b]fluoranthene Does Not Induce Mutations in MutaMouse Male Germ Cells. Reprod Toxicol, 2025, 137:108985 http://doi.org/10.1016/j.reprotox.2025.108985 勘误：长期接触苯并[b]荧光蒽不会诱导突变小鼠雄性生殖细胞发生突变。中华生殖医学杂志，2015,37:108985 https://doi.org/10.1016/j.reprotox.2025.108985。

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2026-03-01 Epub Date: 2025-12-12 DOI: 10.1016/j.reprotox.2025.109138

Madison T. Stewart, Gu Zhou, Danielle P.M. LeBlanc, Annette E. Dodge, Matthew J. Meier, Andrew Williams, Alexandra S. Long, Paul A. White, Carole L. Yauk, Francesco Marchetti

引用次数: 0

Corrigendum to “Hypothesis-driven approach to developmental toxicity assessment: Using mechanistic information to inform testing” [Reprod. Toxicol. 140 (2026) 109119] “假设驱动的发育毒性评估方法：使用机制信息为测试提供信息”的勘误表。中国生物医学工程学报，2014(5):391 - 391。

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2026-03-01 Epub Date: 2025-12-26 DOI: 10.1016/j.reprotox.2025.109144

George Daston , Matthew Burbank , Florian Gautier , Barbara F. Hales , Amer Jamalpoor , Yasunari Kanda , Susan Makris , Aldert H. Piersma , Nicola Powles-Glover , Sonya Sobrian , Vicki Sutherland , Steven Van Cruchten , Ronald L. Wange , Connie L. Chen

引用次数: 0

Effects of dexamethasone on luteal steroidogenesis, cell apoptosis and PKA/CREB/PPARG pathway in rats 地塞米松对大鼠黄体甾体生成、细胞凋亡及PKA/CREB/PPARG通路的影响。

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2026-03-01 Epub Date: 2026-01-09 DOI: 10.1016/j.reprotox.2026.109166

Jie Zhao , Xianyi Zhou , Hao Yu , Abdul Quddus , Xin Liu , Dagan Mao

This study aimed to investigate effects of dexamethasone (Dex) on luteal steroidogenesis, cell apoptosis and PKA/CREB/PPARG pathway in rats. Rats aged 28 days were treated with PMSG and hCG to obtain amounts of corpora lutea, followed by injections of Dex (Dex group) or saline (Control, Con group) for 7 days. Serum was collected to detect biochemical indices with corresponding kits and progesterone (P4) levels by RIA. Ovaries were collected for HE, IHC and TUNEL analysis, and genes and proteins associated with steroidogenesis and apoptosis, including PKA/CREB/PPARG members using real-time PCR and western blotting, respectively. Results showed that Dex treatment increased serum triglyceride and glucose levels (P < 0.05), and decreased high－density lipoprotein cholesterol and low－density lipoprotein cholesterol levels (P < 0.05). Dex treatment increased serum P4 level (P < 0.05), as well as ovarian mRNA abundances of Star and Cyp11a1 (P < 0.05), and protein levels of StAR and HSD3B (P < 0.05); Dex also increased the Bax/Bcl-2 ratio at both mRNA and protein levels (P < 0.05), with a greater incidence of apoptosis confirmed by BAX immunostaining and TUNEL assay. Dex treatment increased the mRNA abundances and protein levels of PKA/CREB/PPARG members (P < 0.05). IHC analysis showed that PPARG was localized in the nuclei as well as cytoplasm of luteal cells. Overall, Dex concurrently stimulated luteal steroidogenesis and apoptosis, likely by the activation of PKA/CREB/PPARG pathway, providing novel insights into stress-related glucocorticoids on luteal function, and reproductive health in mammals under stress or therapeutic glucocorticoid treatment.

本研究旨在探讨地塞米松（Dex）对大鼠黄体甾体生成、细胞凋亡及PKA/CREB/PPARG通路的影响。28日龄大鼠经PMSG和hCG处理获得一定量的黄体，然后注射右美托咪唑（右美托咪唑组）或生理盐水（对照组，对照组），持续7 d。采集血清，采用相应试剂盒检测生化指标，RIA检测孕酮（P4）水平。收集卵巢进行HE、IHC和TUNEL分析，并分别采用real-time PCR和western blotting检测与甾体生成和凋亡相关的基因和蛋白，包括PKA/CREB/PPARG成员。结果显示，右美托咪唑治疗大鼠血清甘油三酯和葡萄糖水平升高（P < 0.05），高密度脂蛋白胆固醇和低密度脂蛋白胆固醇水平降低（P < 0.05）。Dex组血清P4水平升高（P < 0.05），卵巢Star、Cyp11a1 mRNA丰度升高（P < 0.05）， Star、HSD3B蛋白水平升高（P < 0.05）；Dex在mRNA和蛋白水平上均提高了Bax/Bcl-2比值(P

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引用次数: 0

Reduced food consumption triggers abortion in antibiotic-treated pregnant rabbits: Insights from a pair-feeding study 减少食物消耗触发流产的怀孕兔子抗生素治疗：从一对喂养研究的见解

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2026-03-01 Epub Date: 2026-01-28 DOI: 10.1016/j.reprotox.2026.109176

Toshiki Matsuoka , Yoshiko Ohshima , Kumi Honda , Makoto Shirai , Ken Sakurai , Chiharu Kuwata

In embryo-fetal developmental toxicity studies in rabbits, antibiotic administration is often accompanied by reduced food consumption and abortion. This study aimed to investigate whether reduced food consumption, independent of antibiotic exposure, was sufficient to induce abortion and explore potential mechanisms. Pregnant rabbits were assigned to three groups (n = 5/group): oral administration of the fluoroquinolone antibiotic DC-159a group, a pair-fed group receiving the same daily amount of diet as the DC-159a group, and a control group fed ad libitum. DC-159a administration from gestational days 6–18 caused a marked and sustained reduction in food consumption and abortion in all dams. Notably, all pair-fed dams also aborted. Changes in blood chemistry consistent with undernutrition were observed in both groups. Serum progesterone began to decline several days before abortion, and ovarian histopathology suggested luteal dysfunction. These findings indicate that reduced food consumption is the primary trigger of abortion in rabbits treated with DC-159a, indicating the involvement of compromised luteal function under nutritional stress.

在兔的胚胎-胎儿发育毒性研究中，抗生素的使用通常伴随着食物消耗的减少和流产。本研究旨在探讨在不依赖抗生素暴露的情况下，减少食物摄入是否足以诱导流产，并探讨可能的机制。将妊娠兔分为三组（n = 5只/组）：口服氟喹诺酮类抗生素DC-159a组，与DC-159a组日饲料量相同的配对喂养组，自由采食对照组。在妊娠6-18天服用DC-159a后，所有母鼠的食物消耗和流产率显著且持续下降。值得注意的是，所有成对供水的大坝也都夭折了。两组患者的血液化学变化与营养不良一致。流产前几天血清黄体酮开始下降，卵巢组织病理学提示黄体功能障碍。这些发现表明，食物消耗减少是DC-159a治疗家兔流产的主要触发因素，表明营养应激下黄体功能受损的参与。

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引用次数: 0

Endocrine-disrupting effects of titanium dioxide nanoparticles on the female reproductive system: Evidence from an ovariectomized rat model 二氧化钛纳米颗粒对雌性生殖系统的内分泌干扰作用：来自去卵巢大鼠模型的证据。

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology

Pub Date : 2026-03-01 Epub Date: 2025-12-22 DOI: 10.1016/j.reprotox.2025.109147

Z.G. Yurtgezen , M. Sapmaz-Metin , D. Ercetin

Background

Titanium dioxide nanoparticles (TiO₂NPs) are widely used metal nanoparticles capable of accumulating in tissues and exerting endocrine-disrupting effects. Their impact on female reproductive physiology remains largely unclear. This study aimed to elucidate the endocrine-disrupting properties of TiO₂NPs by assessing ovarian and uterine histology, serum hormone levels, estrous cycle changes, and receptor expression patterns in both intact and ovariectomized female rats.

Methods

Thirty-two Sprague Dawley rats were randomly divided into four groups (n = 8/group): intact control, intact TiO₂NP (10 mg/kg/day, oral, 30 days), ovariectomized control (OvX), and OvX + TiO₂NP (10 mg/kg/day, oral). Vaginal cytology was monitored for 10 days. ELISA measured serum estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels. Ovarian and uterine tissues were examined histologically and immunohistochemically for estrogen-receptor alpha (ERα), estrogen-receptor beta (ERβ), luteinizing hormone receptor (LHR), and follicle-stimulating hormone receptor (FSHR) expression.

Results

TiO₂NP exposure elevated estradiol levels in both intact and ovariectomized rats. While ovariectomy significantly increased LH and FSH, TiO₂NP treatment normalized these levels in OvX rats. Ovarian changes included an increase in atretic follicles and a reduction in hormone receptor expression, whereas uterine tissues showed greater gland number, endometrial thickness, and receptor positivity. Estrous cycles were absent in OvX rats but reappeared with prolonged length and estrus frequency in the OvX + TiO₂NP group.

Conclusion

TiO₂NPs exert estrogen-like effects and modulate gonadotropin release through the hypothalamic–pituitary axis, even without ovarian estrogen, indicating pronounced endocrine-disrupting effects on the female reproductive system.

背景：二氧化钛纳米颗粒（TiO₂NPs）是一种应用广泛的金属纳米颗粒，能够在组织中积累并发挥内分泌干扰作用。它们对女性生殖生理的影响在很大程度上仍不清楚。本研究旨在通过评估完整和去卵巢雌性大鼠卵巢和子宫组织学、血清激素水平、发情周期变化和受体表达模式来阐明TiO₂NPs的内分泌干扰特性。方法：32只Sprague Dawley大鼠随机分为4组（n=8/组）：完整对照组、完整TiO₂NP （10mg/kg/d，口服，30 d）、去卵巢对照组（OvX）和OvX + TiO₂NP （10mg/kg/d，口服）。阴道细胞学监测10天。ELISA检测血清雌二醇、促黄体生成素（LH）和促卵泡激素（FSH）水平。采用组织学和免疫组织化学方法检测卵巢和子宫组织中雌激素受体α (ERα)、雌激素受体β (ERβ)、促黄体生成素受体（LHR）和促卵泡激素受体（FSHR）的表达。结果：TiO₂NP暴露可提高未切除卵巢和未切除卵巢大鼠的雌二醇水平。虽然卵巢切除术显著增加了黄体生成素和卵泡刺激素，但在OvX大鼠中，TiO₂NP治疗使这些水平正常化。卵巢变化包括闭锁卵泡增加和激素受体表达减少，而子宫组织显示出更多的腺体数量、子宫内膜厚度和受体阳性。OvX大鼠无发情周期，但OvX + TiO₂NP组出现发情周期，发情周期延长，发情频率增加。结论：即使没有卵巢雌激素，TiO₂NPs也能通过下丘脑-垂体轴调节促性腺激素的释放，对女性生殖系统具有明显的内分泌干扰作用。

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引用次数: 0