Reproductive biology最新文献_第9页

Analyzing the toxicological effects of PET-MPs on male infertility: Insights from network toxicology, mendelian randomization, and transcriptomics 分析PET-MPs对男性不育的毒理学影响：来自网络毒理学、孟德尔随机化和转录组学的见解

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-09-09 DOI: 10.1016/j.repbio.2025.101076

Yang Yang , Linfeng Li , Ning Zhang , Zheng Zhang , Zhengyang Wu , Dongmei Ji

Current research indicates that polyethylene terephthalate microplastics (PET-MPs) may significantly impair male reproductive function. This study aimed to investigate the potential molecular mechanisms underlying this impairment. Potential gene targets of PET-MPs were predicted via the SwissTargetPrediction database. GWAS summary statistics for male infertility were obtained from the GWAS Catalog, and eQTL data were acquired from the eQTLGen database. SMR analysis was subsequently performed to identify genes exhibiting significant causal associations with male infertility. The potential targets of PET-MPs contributing to male infertility were ultimately identified by intersecting the two gene sets. Additionally, bulk RNA-seq and scRNA-seq analyses were employed to elucidate the potential molecular mechanisms underlying PET-MPs-induced male infertility. Our findings suggest that CLK4 may serve as a functional target through which PET-MPs contribute to male infertility, with elevated CLK4 expression representing a significant risk factor. Molecular docking and molecular dynamics simulations demonstrated that PET-MPs can form stable binding conformations with the CLK4 protein. We further identified terminally differentiated CD4⁺ T cells as a prominent risk factor for male infertility, revealing a significant positive correlation between CLK4 expression levels and Th1 cell infiltration. Additionally, CLK4 exhibited a biphasic expression pattern during spermatocyte-to-sperm differentiation, initially increasing before subsequent downregulation. These observations indicate that PET-MPs may participate in the pathogenesis of male infertility by targeting CLK4 to modulate Th1 cell infiltration and disrupt normal spermatogenic processes. In conclusion, our study demonstrates that CLK4 may serve as a potential target for PET-MP-induced male infertility, and we further elucidate the underlying molecular mechanisms.

目前的研究表明，聚对苯二甲酸乙二醇酯微塑料（PET-MPs）可能严重损害男性生殖功能。本研究旨在探讨这种损伤的潜在分子机制。通过SwissTargetPrediction数据库预测PET-MPs的潜在基因靶点。男性不育的GWAS汇总统计数据来自GWAS目录，eQTL数据来自eQTLGen数据库。随后进行SMR分析，以确定与男性不育有显著因果关系的基因。PET-MPs导致男性不育的潜在靶标最终通过交叉两个基因集确定。此外，大量RNA-seq和scRNA-seq分析被用于阐明pet - mps诱导男性不育的潜在分子机制。我们的研究结果表明，CLK4可能是PET-MPs导致男性不育的一个功能靶点，CLK4表达升高是一个重要的危险因素。分子对接和分子动力学模拟表明PET-MPs可以与CLK4蛋白形成稳定的结合构象。我们进一步发现终末分化的CD4+ T细胞是男性不育的重要危险因素，揭示了CLK4表达水平与Th1细胞浸润之间的显著正相关。此外，CLK4在精细胞向精子分化过程中表现出双相表达模式，最初升高，随后下调。这些观察结果表明，PET-MPs可能通过靶向CLK4调节Th1细胞浸润和破坏正常的生精过程参与男性不育的发病机制。总之，我们的研究表明CLK4可能是pet - mp诱导的男性不育的潜在靶点，我们进一步阐明了潜在的分子机制。

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引用次数: 0

Pasteurized Akkermansia muciniphila ameliorates insulin resistance by reducing placental inflammation in GDM mouse model 巴氏灭菌的嗜粘阿克曼氏菌通过减少GDM小鼠模型的胎盘炎症改善胰岛素抵抗

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-09-04 DOI: 10.1016/j.repbio.2025.101073

Yi Wang , Yuting Zhu , Yan Cui , Jiali Fang , Hong Zhong , Yujie Shi , Lan Liu , Xianwei Cui

Gestational diabetes mellitus (GDM) is a common and serious complication during pregnancy. Depleted next-generation probiotic, Akkermansia muciniphila (AKK) in GDM women indicates its potential on GDM prevention. However, the functions and mechanisms of AKK on GDM remain unclear. Due to the limited strategies for GDM therapy, combined with the anaerobic properties of AKK, herein, we reported pasteurized AKK functions as novel postbiotics which ameliorated glucose intolerance and insulin resistance in the GDM mouse model induced by high-fat diet (HFD) feeding combined with STZ. The oral administration of pasteurized AKK enhanced glucose homeostasis and alleviated placental inflammation in the GDM mouse model. Specifically, placental macrophage polarization was transferred by AKK treatment. In addition, the outer membrane protein of AKK, Amuc_1100, mimicked anti-inflammatory properties and improvement of GDM, which served as an effector protein. These findings demonstrate that oral AKK supplementation alleviated placental inflammatory responses through modulating macrophage polarization. Mechanically, we uncovered that a heat-stable outer membrane protein of AKK, Amuc_1100, mimics the anti-diabetic properties of pasteurized AKK through oral administration. Taken together, our findings demonstrated an effective treatment of GDM from the perspective of potential probiotic agents.

妊娠期糖尿病（GDM）是妊娠期常见且严重的并发症。GDM女性中缺失的下一代益生菌AKK （Akkermansia muciniphila， AKK）显示了其预防GDM的潜力。然而，AKK在GDM中的作用和机制尚不清楚。由于GDM治疗策略有限，结合AKK的厌氧特性，本文报道了巴氏杀菌AKK作为一种新型后生物制剂，可以改善高脂肪饮食（HFD）喂养联合STZ诱导的GDM小鼠模型中的葡萄糖耐受不良和胰岛素抵抗。在GDM小鼠模型中，口服巴氏灭菌的AKK可增强葡萄糖稳态并减轻胎盘炎症。具体而言，AKK治疗可转移胎盘巨噬细胞极化。此外，AKK的外膜蛋白Amuc_1100具有模拟抗炎和改善GDM的作用，是一种效应蛋白。这些结果表明，口服AKK补充剂通过调节巨噬细胞极化来减轻胎盘炎症反应。机械地，我们发现AKK的热稳定外膜蛋白Amuc_1100通过口服来模拟巴氏杀菌AKK的抗糖尿病特性。综上所述，我们的研究结果从潜在益生菌制剂的角度证明了GDM的有效治疗。

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引用次数: 0

Evaluation of the protective effect of resveratrol-loaded solid lipid nanoparticles on radiation- or doxorubicin-induced spermatogenic damage in mice 白藜芦醇载固体脂质纳米颗粒对辐射或阿霉素诱导小鼠生精损伤的保护作用评价

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-09-04 DOI: 10.1016/j.repbio.2025.101058

Mohammad Farhadi Rad , Faranak Aghaz , Khodabakhsh Rashidi , Sousan Gharibnejad , Elham Arkan , Kamran Mansouri , Elahe Motevaseli , Masoud Najafi

Radiation and doxorubicin (Dox) exert destructive effects on testicular tissue. Resveratrol, a natural antioxidant, may protect the spermatogenic system against the toxic effects of these agents. This study evaluated the protective and antioxidant properties of resveratrol-loaded solid lipid nanoparticles (RES-SLNs) against Dox- and radiation-induced testicular injury in mice. Following the synthesis of RES-SLNs and characterization of their physicochemical properties, 60 adult male mice were randomly assigned to six groups (n = 10 per group): control, RES-SLNs, Dox, radiation (Rad), RES-SLNs + Dox, and RES-SLNs + Rad. Five mice from each group underwent anesthesia and bilateral orchiectomy for determination of malondialdehyde (MDA) and superoxide dismutase (SOD) levels. The remaining mice were sacrificed for histopathological evaluation of testicular tissue. Radiation and Dox administration significantly increased MDA levels, reduced SOD activity, and altered histological parameters. In contrast, intraperitoneal RES-SLN administration significantly lowered MDA levels, enhanced SOD activity, and mitigated morphological alterations induced by radiation or Dox. These findings indicate that RES-SLNs attenuate oxidative stress in the testes caused by radiation or Dox, thereby preventing severe structural damage.

辐射和阿霉素（Dox）对睾丸组织具有破坏性作用。白藜芦醇是一种天然的抗氧化剂，可以保护生精系统免受这些药物的毒性作用。本研究评估了白藜芦醇负载的固体脂质纳米颗粒（RES-SLNs）对Dox和辐射诱导的小鼠睾丸损伤的保护和抗氧化性能。在合成RES-SLNs并对其理化性质进行表征后，将60只成年雄性小鼠随机分为6组（每组 = 10只）：对照组、RES-SLNs、Dox、辐射（Rad）、RES-SLNs + Dox和RES-SLNs + Rad。每组5只小鼠麻醉后切除双侧睾丸，测定丙二醛（MDA）和超氧化物歧化酶（SOD）水平。其余小鼠处死，进行睾丸组织病理检查。辐射和Dox给药显著增加MDA水平，降低SOD活性，改变组织学参数。相比之下，腹腔注射RES-SLN可显著降低MDA水平，增强SOD活性，减轻辐射或Dox引起的形态学改变。这些发现表明，res - sln可减轻辐射或Dox引起的睾丸氧化应激，从而防止严重的结构损伤。

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引用次数: 0

The ameliorative effects of L-arginine on testicular and genotoxic toxicity induced by chronic exposure to cadmium chloride in male murine models l -精氨酸对慢性氯化镉暴露雄性小鼠睾丸及遗传毒性的改善作用

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-08-29 DOI: 10.1016/j.repbio.2025.101072

Nasibeh Hemati , Milad Chahardori , Mohammad Hosseinzadeh , Fereshteh Taleb-Pour , Fatemeh Shaki

Cadmium (Cd) is a toxic heavy metal known to cause DNA damage, genetic alterations, and reproductive issues in males through free radical production. This study investigates L-arginine, an amino acid with antioxidant and metal-chelating properties, in mitigating Cd-induced genetic and reproductive toxicity in male mice. Thirty-six male mice were divided into six groups: a control group, a Cd group (2 mg/kg), three groups receiving Cd (2 mg/kg) combined with L-arginine (50, 100, 200 mg/kg), and a positive control group receiving vitamin C (500 mg/kg) with Cd. After 42 days, oxidative stress markers, including ROS, protein carbonyl, lipid peroxidation, and glutathione levels, were assessed in bone marrow and testicular tissue. Sperm parameters and histopathological evaluations of testes were also conducted. Chronic Cd exposure significantly reduced glutathione levels and increased oxidative stress markers in both tissues. Sperm count and motility decreased, while abnormal sperm increased. Conversely, L-arginine treatment notably reduced oxidative stress markers, improved antioxidant levels, sperm quality, and testicular histopathology compared to the Cd group. Additionally, Cd exposure increased the number of micronuclei in polychromatic erythrocytes (PCEs), which decreased with L-arginine treatment, enhancing the PCE/(PCE+normochromatic erythrocytes) ratio. These findings suggest that L-arginine effectively mitigates Cd-induced toxicity. The results indicate that L-arginine has significant protective effects against Cd-induced reproductive and bone marrow toxicity.

镉（Cd）是一种有毒的重金属，已知会通过自由基的产生导致DNA损伤、基因改变和男性生殖问题。l-精氨酸是一种具有抗氧化和金属螯合特性的氨基酸，它可以减轻cd对雄性小鼠的遗传和生殖毒性。将36只雄性小鼠分为6组：对照组、Cd组（2 mg/kg）、Cd组（2 mg/kg）联合l -精氨酸组（50、100、200 mg/kg）和维生素C阳性对照组（500 mg/kg）联合Cd。42 d后，测定骨髓和睾丸组织中氧化应激标志物（ROS、蛋白羰基、脂质过氧化和谷胱甘肽）水平。还进行了精子参数和睾丸组织病理学评估。慢性Cd暴露显著降低了两个组织中的谷胱甘肽水平并增加了氧化应激标志物。精子数量和活力下降，而异常精子增加。相反，与Cd组相比，l -精氨酸处理显著降低了氧化应激标志物，提高了抗氧化水平，精子质量和睾丸组织病理学。此外，Cd暴露增加了多染红细胞（PCE）的微核数量，l -精氨酸处理降低了PCE/（PCE+正染红细胞）的比例。这些发现表明l -精氨酸可以有效减轻cd诱导的毒性。结果表明，l -精氨酸对cd诱导的生殖毒性和骨髓毒性具有显著的保护作用。

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引用次数: 0

Fisetin attenuates the adverse effects of freezing and thawing procedures on the biological characteristics of human asthenoteratozoospermia samples 非瑟酮可减轻冷冻和解冻过程对人类弱异精子症样本生物学特性的不利影响

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-08-27 DOI: 10.1016/j.repbio.2025.101060

Daniyal Ezati , Reyhane Vardiyan , Ali Reza Talebi , Fatemeh Alipour , Hasan Pahang , Shabnam Mohammadi

Sperm cryopreservation is a conventional method to preserve sperm cells for a long time. This technique may cause various effects on sperm parameters. Therefore, applying beneficial antioxidants to decrease the adverse effects of freezing is noteworthy. Fisetin is a compound with antioxidant and anti-inflammatory properties. The main aim of the present study is to investigate the protective and beneficial effects of fisetin against cryo-damage on sperm functional parameters. In this experimental study, we analyzed 20 semen samples from asthenoteratozoospermic (AT) patients. Each sample was divided into three treatment groups: (1) fresh control (non-frozen), (2) cryopreservation medium (without fisetin), and (3) cryomedium supplemented with 50 μM fisetin. Freezing and thawing procedures were performed via the conventional method. Post-thaw analyses revealed that cryopreservation significantly reduced sperm motility, chromatin integrity, and mitochondrial membrane potential while increasing DNA fragmentation, malondialdehyde (MDA) levels, and apoptosis (p < 0.05). Fisetin supplementation markedly improved progressive motility (p < 0.05), reduced non-motile sperm percentage (p < 0.05), and decreased DNA fragmentation and MDA levels (p < 0.05). Additionally, it enhanced chromatin condensation and reduced apoptosis rates (p < 0.05). Fisetin attenuates cryo-damage through its antioxidant and anti-apoptotic properties, improving post-thaw sperm quality. Thus, incorporating fisetin into cryopreservation media could enhance sperm viability for assisted reproductive technologies (ART).

精子低温保存是一种长期保存精子细胞的传统方法。这项技术可能会对精子参数产生各种影响。因此，应用有益的抗氧化剂来减少冷冻的不利影响是值得注意的。非瑟酮是一种具有抗氧化和抗炎特性的化合物。本研究的主要目的是探讨非瑟酮对精子功能参数的保护和有益作用。在本实验研究中，我们分析了20例无畸形精子症（AT）患者的精液样本。每个样品分为三个处理组：(1)新鲜对照（不冷冻），(2)低温保存培养基（不含非瑟酮），(3)添加50 μM非瑟酮的低温培养基。冷冻和解冻程序通过常规方法进行。解冻后分析显示，冷冻保存显著降低了精子活力、染色质完整性和线粒体膜电位，同时增加了DNA断裂、丙二醛（MDA）水平和细胞凋亡（p <； 0.05）。补充非瑟酮可显著提高进行性运动能力（p <； 0.05），降低非运动精子百分比（p <； 0.05），降低DNA片段化和MDA水平（p <； 0.05）。此外，它还能增强染色质凝聚，降低细胞凋亡率（p <； 0.05）。非瑟酮通过其抗氧化和抗凋亡特性减轻低温损伤，改善解冻后精子质量。因此，在低温保存培养基中加入非瑟酮可以提高辅助生殖技术（ART）的精子存活率。

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引用次数: 0

Molecular docking of nano-curcumin to caspase-3 and caspase-9: Unraveling its cryoprotective mechanism in rabbit sperm extenders 纳米姜黄素与caspase-3和caspase-9的分子对接：揭示其在兔精子扩展器中的冷冻保护机制

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-08-26 DOI: 10.1016/j.repbio.2025.101071

Abdel-Khalek Kh A E. , Saima Qadeer , Sh.A. Gabr , A.M. Shehabeldin , A.E.B. Ghodaia , Sara Latif , Asma Ul Husna

This study aimed to investigate the cryoprotective mechanism of nano-curcumin (CRNPs) on rabbit sperm via molecular docking and to compare the effects of two extenders, Tris-egg yolk (TEYE) and Tris-soybean lecithin (TSBLE) supplemented with CRNPs on post thaw sperm quality. Molecular docking revealed strong binding of nano-curcumin to Caspase-3 and Caspase-9, suggesting its potential to inhibit pro-apoptotic activity. In silico toxicological profiling predicted a low acute toxicity for nano-curcumin (LD₅₀ = 2000mg/kg; class4). Semen from ten white New Zealand rabbits was collected and pooled, then divided between TEYE and TSBLE. Each extender was further supplemented with CRNPs (0, 1.5, 2 and 2.5 µg/mL). After equilibration, samples were cryopreserved and evaluated post-thaw using CASA and flow cytometry. Supplementation with 1.5 µg/mL CRNPs significantly (p < 0.05) improved total, progressive, and rapid motility, normal morphology, motion velocities, and viability compared to the control. Although reductions in immotility, abnormal forms, apoptosis, and necrosis were observed, these differences were not significant (p > 0.05). Both extenders significantly (p < 0.05) enhanced antioxidant defense by increasing TAC, GPx, and SOD levels while reducing MDA and H₂O₂, with TSBLE showing slightly better performance. In conclusion, CRNPs at 1.5 µg/mL improved sperm motility, viability, morphology, and antioxidant status, likely by mitigating oxidative stress and apoptosis via caspase inhibition. Both extenders were effective, and further in vivo studies are needed to assess fertility outcomes.

本研究旨在通过分子对接的方法探讨纳米姜黄素（CRNPs）对兔精子的冷冻保护机制，并比较添加CRNPs的tris -蛋黄（TEYE）和tris -大豆卵磷脂（TSBLE）两种扩展剂对解冻后精子质量的影响。分子对接发现，纳米姜黄素与Caspase-3和Caspase-9有较强的结合，提示其具有抑制促凋亡活性的潜力。硅毒性分析预测纳米姜黄素具有较低的急性毒性（LD50 = 2000mg/kg; 4）。收集10只新西兰白兔的精液，将其分成TEYE和TSBLE两组。每种扩展剂进一步添加CRNPs（0、1.5、2和2.5 µg/mL）。平衡后，样品冷冻保存，解冻后用CASA和流式细胞术评估。与对照组相比，补充1.5 µg/mL CRNPs显著（p <； 0.05）改善了总运动、进行性运动和快速运动、正常形态、运动速度和活力。虽然观察到运动障碍、异常形态、细胞凋亡和坏死的减少，但这些差异并不显著（p >； 0.05）。两种扩展剂均显著（p <； 0.05）通过提高TAC、GPx和SOD水平，降低MDA和H2O2水平来增强抗氧化防御，其中TSBLE的性能略好。总之，1.5 µg/mL的CRNPs可以改善精子活力、活力、形态和抗氧化状态，可能是通过抑制caspase来减轻氧化应激和细胞凋亡。这两种扩展剂都是有效的，需要进一步的体内研究来评估生育结果。

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引用次数: 0

Potential novel biomarkers for gestational diabetes mellitus in first and early second trimesters: A comprehensive review 妊娠早期和早期妊娠中期糖尿病潜在的新型生物标志物：全面综述

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-08-26 DOI: 10.1016/j.repbio.2025.101059

Rabail Azhar Iqbal , Sophia Nazir

Gestational diabetes mellitus (GDM) is one of the commonly encountered medical disorders of pregnancy affecting women of childbearing age globally at an alarming rate and causing significant perinatal morbidity and adverse fetal outcomes. The intricate interchanges between genetic susceptibility, metabolic changes and environmental factors contribute to the altered β-cell function, insulin sensitivity and glucose metabolism leading to hyperglycaemia in pregnancy. However, the precise etiology of GDM remains incompletely understood. There is a compelling need for the identification of GDM in at-risk pregnant females at an early stage to improve maternal and fetal outcomes. Ongoing research has revealed numerous biomarkers that can be both predictive and diagnostic for GDM. This review aims to explore the various biomarkers that have increasing evidence for their use as predictors of GDM in the first and early second trimesters. The sensitivity, specificity, accuracy, and predictive power of these biomarkers have been compared to identify the ideal candidate(s), despite the effect of confounding factors. Throughout this review, research gaps were highlighted and future research directions were suggested to accurately diagnose GDM through a panel of efficacious biomarkers well before the disease manifests in later pregnancy.

妊娠期糖尿病（GDM）是影响全球育龄妇女的常见妊娠医学疾病之一，发病率惊人，可导致严重的围产期发病率和不良胎儿结局。遗传易感性、代谢变化和环境因素之间复杂的相互作用导致妊娠期β细胞功能、胰岛素敏感性和葡萄糖代谢的改变，从而导致高血糖。然而，GDM的确切病因尚不完全清楚。迫切需要在早期阶段识别高危孕妇的GDM，以改善母体和胎儿的结局。正在进行的研究已经揭示了许多可以预测和诊断GDM的生物标志物。本综述旨在探讨各种生物标志物，越来越多的证据表明，它们可以作为妊娠早期和早期妊娠中期GDM的预测指标。这些生物标志物的敏感性、特异性、准确性和预测能力进行了比较，以确定理想的候选物，尽管存在混杂因素的影响。在这篇综述中，强调了研究的空白，并建议未来的研究方向是在妊娠后期疾病出现之前，通过一组有效的生物标志物准确诊断GDM。

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引用次数: 0

Diurnal variation in clock gene expression and progesterone secretion is inhibited under constant light conditions in Japanese Black cows 恒定光照条件下，日本黑牛生物钟基因表达和黄体酮分泌的日变化受到抑制

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-08-19 DOI: 10.1016/j.repbio.2025.101056

Tsuyoshi Otsuka , Hiroki Mitsuishi , Hiroki Onishi , Masato Yayota

The circadian clock is constructed by a transcription–translation feedback loop system of clock genes and regulates various reproductive physiological functions. Understanding the rhythms of clock gene expression is important for understanding biological rhythms. However, the in vivo clock gene expression rhythm in Japanese Black breeding cows has not yet been clarified. Herein, we investigated the circadian expression rhythm of clock genes in hair follicle cells in the hair roots of Japanese Black breeding cows. We found that the clock genes of Japanese Black breeding cows exhibit an expression rhythm with a period of approximately 24 h under natural light, similar to the pattern observed in mice and humans, and that this expression rhythm disappears under constant light conditions. Furthermore, since the expression levels of clock genes are significantly reduced in pregnant cows exposed to constant light conditions, we analysed the diurnal variation in the plasma concentration of progesterone, which plays an important role in maintaining pregnancy. We found that the progesterone secretion rhythm observed under natural light in pregnant cows also disappeared under constant light conditions. These results indicate that in Japanese Black breeding cows, clock genes exhibit a diurnal expression rhythm in response to light; this rhythm disappears under constant light conditions. These clock genes play important roles in the diurnal variation in hormone secretion by interacting with progesterone in the blood.

生物钟是由生物钟基因的转录-翻译反馈循环系统构成的，调节着各种生殖生理功能。了解生物钟基因表达的节律对于理解生物节律非常重要。然而，日本黑种牛体内时钟基因的表达节律尚未明确。在此，我们研究了日本黑种牛毛根毛囊细胞中时钟基因的昼夜表达节律。我们发现，日本黑奶牛的时钟基因在自然光下的表达周期约为24 h，与小鼠和人类的表达模式相似，而在恒定的光照条件下，这种表达节律消失。此外，由于时钟基因的表达水平在暴露于恒定光照条件下的怀孕奶牛中显著降低，我们分析了血浆中黄体酮浓度的日变化，黄体酮在维持妊娠中起着重要作用。我们发现，在自然光下观察到的孕酮分泌节律在恒定光照条件下也消失了。上述结果表明，日本黑种奶牛生物钟基因在光照条件下表现出昼夜表达节律；这种节奏在恒定的光照条件下消失。这些生物钟基因通过与血液中的黄体酮相互作用，在激素分泌的昼夜变化中发挥重要作用。

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引用次数: 0

Bovine ampullary and isthmic epithelial spheroids: proteomic profile and physiological features for in vitro studies of gamete-oviduct interactions 牛壶腹和峡部上皮球体：配子-输卵管相互作用体外研究的蛋白质组学特征和生理特征

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-08-15 DOI: 10.1016/j.repbio.2025.101057

Coline Mahé , Ludivine Marco , Ludivine Laffont , Marie-Véronique Demattei , Karine Reynaud , Emmanuelle Com , Régis Lavigne , Charles Pineau , Marie Saint-Dizier

After mating or insemination, spermatozoa reach the first part of the oviduct, known as the isthmus, where a subpopulation binds to the epithelial cilia, forming a reservoir. Then, spermatozoa migrate toward the ampulla, where additional interactions with cilia occur and fertilization takes place. Exploring sperm-oviduct interactions requires physiologically relevant in vitro models. Our goal was to characterize isthmic and ampullary epithelial spheroids in terms of cellular, proteomic and sperm binding properties. Spheroids measuring 100–150 µm in diameter, formed after a 3-day culture of pre-ovulatory oviduct mucosa fragments, were selected and analyzed for (i) epithelial, fibroblast and cilia markers by immunostaining, (ii) proteomic content by dia-PASEF nanoLC-MS/MS, and (iii) ability to interact with bull spermatozoa during a 6-h co-culture, assessed by confocal and scanning electron microscopy. Cells within both isthmic and ampullary spheroids showed positive immunostaining for cytokeratin and no staining for vimentin. Ampullary spheroids consistently exhibited a higher proportion of ciliated cells compared to isthmic spheroids (24.5 % vs 20 %; p < 0.05; variation coefficients among replicates of 15 and 11 %, respectively). A total of 6914 proteins were quantified, of which 1010 (14 %) were differentially abundant between isthmic and ampullary spheroids. Following co-culture, 95–97 % of bound spermatozoa were attached by their head to cilia of both spheroid groups. The density of bound spermatozoa was on average 33–45 % higher on ampullary compared to isthmic spheroids (p < 0.001). This study provides a well-differentiated oviduct epithelium model for in vitro investigations of gamete and embryo interactions with the oviduct.

在交配或授精后，精子到达输卵管的第一部分，即峡部，在那里一个亚群与上皮纤毛结合，形成一个储存库。然后，精子向壶腹移动，在那里与纤毛发生额外的相互作用并受精。探索精子-输卵管相互作用需要生理相关的体外模型。我们的目标是在细胞，蛋白质组学和精子结合特性方面表征峡部和壶腹上皮球体。在排卵前输卵管粘膜片段培养3天后形成直径为100-150 µm的球体，选择并分析(i)通过免疫染色检测上皮、成纤维细胞和纤毛标志物，（ii）通过dia-PASEF nanoLC-MS/MS检测蛋白质组学含量，以及（iii）通过共聚焦和扫描电子显微镜评估在6小时共培养过程中与公牛精子相互作用的能力。峡部和壶腹球体内的细胞角蛋白免疫染色阳性，而波形蛋白未染色。壶腹球体比峡部球体始终显示出更高比例的纤毛细胞(24.5% % vs 20% %；p & lt; 0.05;重复间变异系数分别为15和11 %)。共检测到6914个蛋白，其中1010个（14 %）在壶腹和峡部球体之间差异丰富。共培养后，95 - 97% %的结合精子头部附着在两组的纤毛上。壶腹结合精子密度比峡部球体平均高33-45 % （p <； 0.001）。本研究为体外研究配子和胚胎与输卵管的相互作用提供了一个分化良好的输卵管上皮模型。

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Protective role of gallic acid in sperm health and environmentally induced male infertility: A narrative review of human-relevant and translational preclinical studies 没食子酸在精子健康和环境诱导的男性不育中的保护作用：对人类相关和转化性临床前研究的述评

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-08-13 DOI: 10.1016/j.repbio.2025.101055

Weitian Chen , Junfeng Qiu , Zhiming Hong , Jinjun Yuan , Quan Wang , Wenbin Zhou

Male infertility has become a growing global concern due to the decline in sperm quality, largely influenced by environmental toxins, aging, and lifestyle factors. This comprehensive review investigates the potential protective effects of gallic acid (GA), a natural phenolic compound, against various forms of male infertility. GA’s antioxidant, anti-inflammatory, and anti-apoptotic properties are explored in the context of sperm health and reproductive dysfunctions induced by environmental toxins, oxidative stress, and drug treatments. The paper highlights preclinical studies demonstrating GA’s ability to improve sperm quality, enhance testicular function, and restore hormonal balance. Key findings show that GA can mitigate testicular damage, reduce oxidative stress, and promote spermatogenesis in response to stressors such as chemotherapy, phthalates, and nicotine exposure. Moreover, GA’s potential in sperm cryopreservation and fertility preservation is also examined. This review emphasizes the therapeutic promise of GA as a natural agent in supporting male reproductive health and offers insight into its molecular mechanisms. These data collectively justify immediate clinical translation, specifically, well-controlled phase I/II trials that define GA’s optimal dose, safety, pharmacokinetics, and efficacy on validated reproductive endpoints.

由于精子质量下降，很大程度上受环境毒素、衰老和生活方式因素的影响，男性不育症已成为一个日益受到全球关注的问题。这篇综合综述调查了没食子酸（GA），一种天然酚类化合物，对各种形式的男性不育的潜在保护作用。在环境毒素、氧化应激和药物治疗诱导的精子健康和生殖功能障碍的背景下，探讨了GA的抗氧化、抗炎和抗凋亡特性。这篇论文强调了临床前研究表明GA能够改善精子质量，增强睾丸功能，恢复激素平衡。主要研究结果表明，GA可以减轻睾丸损伤，减少氧化应激，促进精子发生，以应对化疗，邻苯二甲酸盐和尼古丁暴露等应激源。此外，还探讨了GA在精子冷冻保存和生育能力保存方面的潜力。这篇综述强调了GA作为一种支持男性生殖健康的天然药物的治疗前景，并提供了其分子机制的见解。这些数据共同证明了立即的临床转化，特别是控制良好的I/II期试验，这些试验确定了GA的最佳剂量、安全性、药代动力学和在经过验证的生殖终点的有效性。

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引用次数: 0