Reproductive biology最新文献_第4页

ProAKAP4 as a potential biomarker of fertility and sperm freezability in males of different species - A review ProAKAP4作为不同物种雄性生殖能力和精子冷冻性的潜在生物标志物的研究进展

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2026-03-01 Epub Date: 2025-12-30 DOI: 10.1016/j.repbio.2025.101176

Paulina Surmacz, Monika Petrajtis-Gołobów, Paula Kiełbik, Katarzyna Siewruk, Ewa Kautz-Wasilewska, Sławomir Giziński

In recent years, special attention has been paid to proAKAP4, the precursor of A-kinase anchoring protein 4 (AKAP4), which plays a crucial role in the structure and function of the sperm flagellum. This testis-specific protein forms the fibrous sheath and local signal transduction required for proper sperm capacitation and motility. Highly conserved across species, proAKAP4 levels are strongly correlated with fertility and sperm survivability post-thaw. This review summarizes the biological roles of proAKAP4 and its potential as a semen quality biomarker in various mammalian species, including humans, horses, bulls, boars, dogs, rodents and other species. We discuss structural and molecular aspects of proAKAP4 (e.g., prodomain, PKA interactions, phosphorylation sites), as well as its involvement in key signaling pathways controlling sperm movement, such as the cAMP-PKA cascade and calcium signaling. The review also outlines various methods for measuring proAKAP4, such as ELISA, Western blotting and immunocytochemistry. Particular attention is given to commercial assays, which allow rapid and species-specific quantification of proAKAP4, independent of seminal plasma or cryoprotectant presence. Although the data are promising, researchers highlight the need for further validation in larger populations under varying environmental conditions. Nonetheless, current findings suggest that proAKAP4 may emerge as a standard marker in andrological diagnostics and a valuable tool for selecting breeding males and optimizing semen cryopreservation procedures.

近年来，a激酶锚定蛋白4 （AKAP4）的前体proAKAP4在精子鞭毛的结构和功能中起着至关重要的作用。这种睾丸特异性蛋白形成纤维鞘和局部信号转导，这是精子获得和运动所需的。proAKAP4在物种间高度保守，其水平与受精能力和解冻后精子存活率密切相关。本文综述了proAKAP4在人类、马、牛、猪、狗、啮齿动物等哺乳动物中的生物学作用及其作为精液质量生物标志物的潜力。我们讨论了proAKAP4的结构和分子方面（如原结构域、PKA相互作用、磷酸化位点），以及它参与控制精子运动的关键信号通路，如cAMP-PKA级联和钙信号传导。本文还概述了检测proAKAP4的各种方法，如ELISA、Western blotting和免疫细胞化学。特别注意的是商业分析，它允许快速和物种特异性定量proAKAP4，独立于精浆或冷冻保护剂的存在。虽然这些数据很有希望，但研究人员强调，需要在不同环境条件下的更大人群中进一步验证。尽管如此，目前的研究结果表明，proAKAP4可能会成为男科诊断的标准标记，以及选择繁殖雄性和优化精液冷冻保存程序的有价值的工具。

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引用次数: 0

The secretome from human amniotic membrane-derived mesenchymal stem cells alleviate oxidative damage in bovine sperm 人羊膜间充质干细胞分泌组可减轻牛精子的氧化损伤

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2026-03-01 Epub Date: 2025-12-31 DOI: 10.1016/j.repbio.2025.101178

Negin Amirjannati , Mohammadmehdi Barfar , Mostafa Pournourali , Niloofar Khalili , Parviz Tajik , Razie Shams , Alireza Jahandideh , Leila Balaei Goli , Seyed Jafar Hashemian , Ablofazl Shirazi , Hannaneh Golshahi

Bovine spermatozoa are highly vulnerable to oxidative stress (OS), which can impair motility, viability, membrane integrity, and DNA integrity. Human amniotic membrane-derived mesenchymal stem cells (AM-MSCs) secrete paracrine factors with antioxidant properties, making their secretome (AM-MSC-Sec) a potential tool for protecting sperm function. This study evaluated the protective effects of AM-MSC-Sec on bovine sperm under OS. Frozen Holstein bull semen was thawed, purified using a two-layer density gradient, and divided into four groups: control (no treatment), H₂O₂ (10 μM), H₂O₂ + 20 % AM-MSC-Sec, and H₂O₂ + 20 % DMEM/F12. After 2 h at 38.5°C and 5 % CO₂, sperm quality parameters—including motility, progressive motility, viability, plasma membrane integrity, acrosome reaction, DNA fragmentation, malondialdehyde (MDA), and total antioxidant capacity (TAC)—were assessed. AM-MSC-Sec significantly improved the percentage of total and progressive motility, enhanced viability and membrane integrity, and decreased DNA fragmentation compared with control and DMEM groups. The percentage of acrosome-reacted sperm increased, and TAC levels were elevated, indicating improved antioxidant defense. DMEM/F12 alone did not show a protective effect. MDA levels increased non-significantly under stress in the control group; however, the difference was not statistically significant. These findings suggest that AM-MSC-Sec could mitigate oxidative damage and preserve multiple functional parameters in bovine sperm. AM-MSC-Sec may serve as a promising therapeutic agent for maintaining sperm quality, with potential applications in bovine reproductive technologies.

牛精子非常容易受到氧化应激（OS）的影响，氧化应激会损害精子的运动性、活力、膜完整性和DNA完整性。人羊膜间充质干细胞（AM-MSCs）分泌具有抗氧化特性的旁分泌因子，使其分泌组（AM-MSCs - sec）成为保护精子功能的潜在工具。本研究评价了AM-MSC-Sec对OS下牛精子的保护作用。冷冻荷斯坦公牛精液解冻，采用双层密度梯度纯化，分为4组：对照组（未处理）、H₂O₂（10 μM）、H₂O₂+ 20 % AM-MSC-Sec和H₂O₂+ 20 % DMEM/F12。在38.5°C和5 % CO₂条件下2 h后，评估精子质量参数，包括运动性、渐进式运动性、活力、质膜完整性、顶体反应、DNA断裂、丙二醛（MDA）和总抗氧化能力（TAC）。与对照组和DMEM组相比，AM-MSC-Sec显著提高了总运动性和进行运动性的百分比，提高了细胞活力和膜完整性，减少了DNA断裂。顶体反应精子的百分比增加，TAC水平升高，表明抗氧化防御能力增强。单独的DMEM/F12没有显示出保护作用。应激条件下，对照组丙二醛水平无明显升高；然而，差异无统计学意义。这些结果表明，AM-MSC-Sec可以减轻牛精子的氧化损伤，并保持多种功能参数。AM-MSC-Sec可能是一种很有前景的精子质量维持剂，在牛生殖技术中具有潜在的应用前景。

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引用次数: 0

Phloretin enhances the efficiency of sheep oocyte IVM and early embryonic development by bolstering antioxidant defenses, inhibiting apoptosis, and promoting development 根皮素通过增强抗氧化防御、抑制细胞凋亡和促进发育来提高绵羊卵母细胞IVM和早期胚胎发育的效率

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2026-03-01 Epub Date: 2025-11-14 DOI: 10.1016/j.repbio.2025.101102

Xu Li , Shuhong Tang , Yinwei Zheng , Ruiguo Zhao , Feifan Xu , Naerhulan Ayiken , Guangdong Hu , Yanping Wang , Weibin Zeng

Phloretin, a natural dihydrochalcone flavonoid, is recognized for its potent antioxidant, anti-apoptotic, and anti-inflammatory properties. This study investigated the effects of phloretin on the in vitro maturation (IVM) of sheep oocytes and subsequent early embryonic development. Treatment with 5 μmol/L phloretin significantly improved the rates of oocyte maturation, cleavage, and blastocyst formation compared to the control group. This treatment also significantly increased intracellular glutathione (GSH) levels and mitochondrial membrane potential (ΔΨm), while reducing reactive oxygen species (ROS) levels. Furthermore, the treatment up-regulated the expression of key antioxidant genes (CAT, SOD2, GPX3) and the follicular development factor gene BMP15. Similarly, supplementing the early embryo culture medium with 5 μmol/L phloretin elevated GSH levels and ΔΨm, and reduced ROS levels in morulae. It also up-regulated the expression of the antioxidant genes CAT, GPX3, and SOD2. Moreover, the treatment enhanced the expression of development-related genes (P53 and OCT4) and significantly decreased the pro-apoptotic Bax/Bcl-2 ratio. In conclusion, phloretin enhances the efficiency of sheep oocyte IVM and early embryonic development by bolstering antioxidant defenses, inhibiting apoptosis, and promoting development. These findings provide a foundation for optimizing in vitro embryo production (IVP) protocols in sheep.

根皮素是一种天然的二氢查尔酮类黄酮，因其有效的抗氧化、抗凋亡和抗炎特性而被公认。本研究探讨了根皮素对绵羊卵母细胞体外成熟（IVM）及随后早期胚胎发育的影响。与对照组相比，5 μmol/L根皮素处理显著提高了卵母细胞成熟、卵裂和囊胚形成的速度。该治疗还显著增加细胞内谷胱甘肽（GSH）水平和线粒体膜电位（ΔΨm），同时降低活性氧（ROS）水平。此外，该处理上调了关键抗氧化基因（CAT、SOD2、GPX3）和卵泡发育因子基因BMP15的表达。同样，在早期胚培养基中添加5 μmol/L根皮素可提高桑葚胚GSH和ΔΨm水平，降低ROS水平。同时上调抗氧化基因CAT、GPX3和SOD2的表达。此外，该治疗提高了发育相关基因（P53和OCT4）的表达，并显著降低了促凋亡的Bax/Bcl-2比值。综上所述，根皮素通过增强抗氧化防御、抑制细胞凋亡和促进发育，提高绵羊卵母细胞IVM和早期胚胎发育效率。这些发现为优化绵羊体外胚胎生产（IVP）方案提供了基础。

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引用次数: 0

The impact of extracellular vesicles on spermatozoa: Navigating toward fertilization 细胞外囊泡对精子的影响：导向受精

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2026-03-01 Epub Date: 2025-10-15 DOI: 10.1016/j.repbio.2025.101090

Saumya Gunasekara , Qurat Ul Ain Reshi , Getnet Midekessa , Suranga Kodithuwakku , Alireza Fazeli , Aneta Andronowska

Reproduction is a complex and highly regulated biological process, underpinned by a range of hormones and unique biological fluids secreted by the reproductive system, including follicular fluid, oviductal fluid, uterine fluid, seminal fluid, amniotic fluid, etc. These fluids not only create an optimal environment by maintaining homeostasis for gamete development and fertilization but also ensure the successful adaptation of the developing embryo to its surrounding environments. Within this intricate network, Extracellular Vesicles (EVs), which are found in reproductive tracts associated biological fluids, have emerged as key players in regulating various reproductive processes. Unlike other micro and macromolecules found in these fluids, EVs are gaining significant attention due to their crucial roles in cellular communication across several biological barriers and their biological compatibility. Therefore, over the past few decades, EVs have emerged as a significant aspect in reproduction-related research, shedding light on underlying physiological mechanisms and harboring potential for clinical applications in fertility diagnosis, treatment, and beyond.

生殖是一个复杂和高度调控的生物过程，由生殖系统分泌的一系列激素和独特的生物液体支撑，包括卵泡液、输卵管液、子宫液、精液、羊水等。这些液体不仅通过维持配子发育和受精的稳态来创造最佳环境，而且还确保发育中的胚胎成功适应周围环境。在这个复杂的网络中，细胞外囊泡（EVs）在生殖道相关的生物液体中被发现，在调节各种生殖过程中起着关键作用。与在这些液体中发现的其他微分子和大分子不同，电动汽车因其在跨越多种生物屏障的细胞通信中发挥的关键作用及其生物相容性而受到广泛关注。因此，在过去的几十年里，ev已经成为生殖相关研究的一个重要方面，揭示了潜在的生理机制，并在生育诊断、治疗等方面具有潜在的临床应用潜力。

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引用次数: 0

Cytotoxicity, antioxidant activity, and gene expression effects of gossypol in primary smooth muscle of myometrium from Ovis aries (PSMo24) cells 棉酚在卵巢肌层原代平滑肌（PSMo24）细胞中的细胞毒性、抗氧化活性和基因表达影响

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2026-03-01 Epub Date: 2025-10-21 DOI: 10.1016/j.repbio.2025.101092

Carolina Rodriguez Jimenez , Bruno Scatena Gatti , Daniela Pimenta , Lívia Presuto , Brenda Luciana Alves da Silva , Patricia Spoto Corrêa , Severino Matias de Alencar , Helder Louvandini

This study aimed to investigate the effects of gossypol on cell viability, oxidative stress, and gene expression in Primary Smooth Muscle of Myometrium from Ovis aries (PSMo₂₄) Cells. The cells were cultured and treated with varying concentrations of gossypol (1–2000 µg/mL), cytotoxicity was assessed using the MTT assay, oxidative stress were evaluated by fluorescence-based methods (DCFH-DA/ABAP), and the expression of structural, hormonal, apoptotic, and antioxidant genes was analyzed by RT-qPCR. The results showed that concentrations ≤ 5 µg/mL gossypol (G5) maintained cell viability, whereas higher doses induced a progressive loss of viability, indicating dose-dependent cytotoxicity. The production of reactive oxygen species was not significantly affected, suggesting that gossypol did not exhibit relevant antioxidant or pro-oxidant activity at the tested doses. Gene expression analysis revealed differential regulation of β-actin, myosin light chain kinase (MLCK), progesterone receptor (PR), estradiol receptor (ER), the pro-apoptotic gene BAX, and the anti-apoptotic gene BCL2. The transition observed between G7, G10, and G15 revealed a functional gradient: G7 reflected a cell survival profile; G10 marked the apoptotic inflection point; and G15 corresponded to programmed cell death. The antioxidant genes remained unchanged, indicating the maintenance of cellular oxidative homeostasis. In conclusion, gossypol induces dose-dependent cytotoxicity in uterine smooth muscle cells (PSMo₂₄), modulating structural, hormonal, and apoptotic genes without altering basal antioxidant activity. Low concentrations were well tolerated, while higher doses from 7 µg/mL activated pro-apoptotic pathways The results highlight the need for caution in reproductive contexts within the animal field and suggest potential use in oncological therapies.

本研究旨在探讨棉酚对卵巢子宫肌平滑肌细胞（PSMo24）细胞活力、氧化应激和基因表达的影响。用不同浓度的棉酚（1-2000µg/mL）培养和处理细胞，用MTT法评估细胞毒性，用荧光法（DCFH-DA/ABAP）评估氧化应激，用RT-qPCR分析结构、激素、凋亡和抗氧化基因的表达。结果表明，浓度≤ 5 µg/mL的棉酚（G5）维持了细胞活力，而更高的剂量会导致细胞活力逐渐丧失，表明剂量依赖性的细胞毒性。活性氧的产生没有受到显著影响，表明棉酚在测试剂量下没有表现出相应的抗氧化或促氧化活性。基因表达分析显示，β-肌动蛋白、肌球蛋白轻链激酶（MLCK）、孕酮受体（PR）、雌二醇受体（ER）、促凋亡基因BAX和抗凋亡基因BCL2均有差异调控。在G7、G10和G15之间观察到的转变揭示了功能梯度：G7反映了细胞存活概况；G10为凋亡拐点；G15对应程序性细胞死亡。抗氧化基因保持不变，表明维持了细胞氧化稳态。综上所述，棉酚在子宫平滑肌细胞（PSMo24）中诱导剂量依赖性细胞毒性，调节结构、激素和凋亡基因，但不改变基础抗氧化活性。低浓度耐受性良好，而7 µg/mL的高剂量激活了促凋亡途径。结果强调了在动物领域生殖环境中需要谨慎，并提示在肿瘤治疗中的潜在应用。

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引用次数: 0

Downregulation of intracellular ATP levels by PANX1 inhibits ovarian granulosa cell proliferation and mediates follicular dysplasia in elderly women PANX1下调细胞内ATP水平可抑制老年女性卵巢颗粒细胞增殖并介导卵泡发育不良。

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2026-03-01 Epub Date: 2025-11-29 DOI: 10.1016/j.repbio.2025.101105

Zhiqin Zhang , Xuechen Sun , Xin Li , Peipei Liu , Liyun Cao , Shenggen Long , Jun Tan

This study examined pannexin 1 (PANX1) expression in ovarian granulosa cells of women with advanced maternal age and its role in cell proliferation and apoptosis, aiming to clarify mechanisms of age-related follicular dysplasia. Ninety women undergoing assisted reproductive technology were divided into reproductive-age (<35 years), advanced-age (35–41 years), and very advanced-age (≥42 years) groups. Clinical data and granulosa cell function were analyzed. PANX1 expression was detected in primary cells, while KGN cells were transfected with PANX1 plasmid or siRNA. Cell proliferation, apoptosis, and extracellular ATP levels were evaluated. With increasing age, oocyte yield, blastocyst formation, and pregnancy rates declined, granulosa cell proliferation decreased, apoptosis increased, and PANX1 expression was elevated. PANX1 overexpression inhibited proliferation and increased extracellular ATP, whereas knockdown enhanced proliferation without affecting apoptosis. PANX1 upregulation in aging granulosa cells mediates ATP efflux, depletes intracellular ATP, and suppresses proliferation, contributing to abnormal follicular development and reduced fertility.

本研究通过检测pannexin 1 （PANX1）在高龄产妇卵巢颗粒细胞中的表达及其在细胞增殖和凋亡中的作用，旨在阐明年龄相关性卵泡发育不良的机制。90名接受辅助生殖技术的妇女被分为育龄(

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引用次数: 0

Biochemical profile of fetal fluids in alpacas (Vicugna pacos) during pregnancy and immediate postpartum 羊驼（Vicugna pacos）孕期和产后胎儿体液的生化特征

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2026-03-01 Epub Date: 2025-12-20 DOI: 10.1016/j.repbio.2025.101172

Joel Iván Pacheco , Hugo Wenceslao Deza , Víctor Manuel Vélez-Marroquín , Wilber García , Francisco Franco , Edward H. Cabezas-Garcia , Daniel Marcelo Lombardo

Pregnancy involves characteristics unique to each species, such as the development of fetal membranes and related fluids. In this descriptive exploratory study, a unique third fetal fluid located under the epidermal membrane, in addition to the allantoic and amniotic membranes, were described in alpacas (Vicugna pacos). The aim was to characterize the biochemical composition of fetal fluids as alpaca gestation progressed. Twenty-seven pregnant alpacas were examined; 21 of them were slaughtered at various pregnancy stages to both collect allantoic and amniotic fluids, and six were monitored until parturition to obtain postpartum allantoic fluid. In the last third of pregnancy, an additional fluid was observed between the fetal skin and the epidermal membrane, herein termed as ‘epidermal fluid’. Biochemical analyses were performed via spectrophotometry to measure glucose, triglycerides, cholesterol, total proteins, albumin, hemoglobin, calcium, phosphorus, uric acid, and creatinine. High variability was observed in all metabolites. Allantoic fluid showed increasing levels of uric acid, creatinine, and calcium throughout pregnancy, suggesting fetal renal function, while postpartum fluid showed reduced levels of several metabolites. The amniotic fluid displayed increased triglycerides and cholesterol, and decreased glucose levels at the end of pregnancy. Epidermal fluid exhibited the highest levels of glucose, calcium, and creatinine, and lowest uric acid compared to amniotic fluid, indicating a distinct biochemical composition. This study provides the first comprehensive insight into the biochemical characterization of fetal fluids in alpacas, updating current knowledge of fetal developmental physiology in South American camelids.

怀孕涉及每个物种特有的特征，如胎膜和相关液体的发育。在这项描述性探索性研究中，在羊驼（Vicugna pacos）中，除了尿囊膜和羊膜外，还发现了位于表皮膜下的独特的第三种胎液。目的是表征羊驼妊娠进展时胎液的生化组成。对27头怀孕的羊驼进行了检查；其中21例在妊娠各阶段屠宰，采集尿囊液和羊水，6例监测至分娩，采集产后尿囊液。在妊娠的最后三分之一，在胎儿皮肤和表皮膜之间观察到一种额外的液体，这里称为“表皮液”。通过分光光度法进行生化分析，测量葡萄糖、甘油三酯、胆固醇、总蛋白、白蛋白、血红蛋白、钙、磷、尿酸和肌酐。在所有代谢物中观察到高变异性。尿囊液显示尿酸、肌酐和钙水平在妊娠期间升高，提示胎儿肾功能，而产后液体显示几种代谢物水平降低。妊娠末期羊水显示甘油三酯和胆固醇升高，葡萄糖水平降低。与羊水相比，表皮液的葡萄糖、钙和肌酐含量最高，尿酸含量最低，这表明表皮液的生化成分不同。这项研究首次全面深入了解了羊驼胎儿体液的生化特征，更新了目前对南美骆驼类胎儿发育生理学的了解。

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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 : 2025-12-01 Epub 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

Exploring critical hub genes and potential drug candidates for PCOS: A systems biology approach 探索多囊卵巢综合征的关键枢纽基因和潜在候选药物：系统生物学方法

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-12-01 Epub Date: 2025-09-27 DOI: 10.1016/j.repbio.2025.101078

Ali Ahmadizad Firouzjaei , Ali Mahmoudi , Natalia Elizova , Prashant Kesharwani , Amirhossein Sahebkar

Polycystic ovarian syndrome (PCOS) is widely recognized as the most common endocrine disorder in women of reproductive age. We aimed to identify PCOS-related genes by searching the Gene Expression Omnibus (GEO) database, and subsequently used the DESeq2 tool in the R program to identify differentially expressed genes. We constructed a protein-protein interaction (PPI) network for the upregulated genes in PCOS and applied the MCODE algorithm to identify significant clustering groups and hub candidates. Additionally, we performed an enrichment analysis using the ClueGO plugin to explore the biological processes and pathways associated with the upregulated genes. We successfully obtained the dataset GSE155489 from the GEO database and identified 198 elevated genes. The biological functions associated with the upregulated genes were predominantly related to steroid binding, chemokine activity, and pyridoxal phosphate binding. Results from the molecular docking study indicated that three drugs, namely Ponatinib, Dihydroergotamine, and Paliperidone, exhibited the lowest binding affinity energy and displayed the highest interaction with the most critical hub genes identified through the PPI network analysis (WNT5A, SERPINE1, and CXCR4). In summary, our findings highlight several crucial genes involved in PCOS and suggest that Ponatinib, Dihydroergotamine, and Paliperidone may have a significant impact on these genes. However, it is important to note that further research and well-designed clinical trials are necessary, as there is limited evidence from small-population clinical trials regarding the repurposing of drugs for PCOS. Advancements in PCOS knowledge will aid in the development of innovative medications for the disorder.

多囊卵巢综合征（PCOS）是公认的育龄妇女最常见的内分泌疾病。我们的目标是通过检索Gene Expression Omnibus （GEO）数据库来鉴定pcos相关基因，随后使用R程序中的DESeq2工具鉴定差异表达基因。我们构建了PCOS中上调基因的蛋白相互作用（protein-protein interaction， PPI）网络，并应用MCODE算法识别显著聚类群和候选中心。此外，我们使用ClueGO插件进行了富集分析，以探索与上调基因相关的生物学过程和途径。我们成功地从GEO数据库中获得了数据集GSE155489，并鉴定出198个升高基因。与上调基因相关的生物学功能主要与类固醇结合、趋化因子活性和磷酸吡哆醛结合有关。分子对接研究结果显示，Ponatinib、dihydro麦角胺和palperidone三种药物的结合亲和能最低，与PPI网络分析发现的最关键枢纽基因（WNT5A、SERPINE1和CXCR4）的相互作用最高。总之，我们的研究结果强调了与PCOS有关的几个关键基因，并表明波纳替尼、双氢麦角胺和帕利哌酮可能对这些基因有重大影响。然而，值得注意的是，进一步的研究和精心设计的临床试验是必要的，因为关于多囊卵巢综合征药物再利用的小人群临床试验证据有限。多囊卵巢综合征知识的进步将有助于开发针对该疾病的创新药物。

{"title":"Exploring critical hub genes and potential drug candidates for PCOS: A systems biology approach","authors":"Ali Ahmadizad Firouzjaei , Ali Mahmoudi , Natalia Elizova , Prashant Kesharwani , Amirhossein Sahebkar","doi":"10.1016/j.repbio.2025.101078","DOIUrl":"10.1016/j.repbio.2025.101078","url":null,"abstract":"<div><div>Polycystic ovarian syndrome (PCOS) is widely recognized as the most common endocrine disorder in women of reproductive age. We aimed to identify PCOS-related genes by searching the Gene Expression Omnibus (GEO) database, and subsequently used the DESeq2 tool in the R program to identify differentially expressed genes. We constructed a protein-protein interaction (PPI) network for the upregulated genes in PCOS and applied the MCODE algorithm to identify significant clustering groups and hub candidates. Additionally, we performed an enrichment analysis using the ClueGO plugin to explore the biological processes and pathways associated with the upregulated genes. We successfully obtained the dataset GSE155489 from the GEO database and identified 198 elevated genes. The biological functions associated with the upregulated genes were predominantly related to steroid binding, chemokine activity, and pyridoxal phosphate binding. Results from the molecular docking study indicated that three drugs, namely Ponatinib, Dihydroergotamine, and Paliperidone, exhibited the lowest binding affinity energy and displayed the highest interaction with the most critical hub genes identified through the PPI network analysis (WNT5A, SERPINE1, and CXCR4). In summary, our findings highlight several crucial genes involved in PCOS and suggest that Ponatinib, Dihydroergotamine, and Paliperidone may have a significant impact on these genes. However, it is important to note that further research and well-designed clinical trials are necessary, as there is limited evidence from small-population clinical trials regarding the repurposing of drugs for PCOS. Advancements in PCOS knowledge will aid in the development of innovative medications for the disorder.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 4","pages":"Article 101078"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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 : 2025-12-01 Epub 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