Reproductive biology最新文献_第8页

Extracellular vesicles derived from placental trophoblast regulate ovine endometrial receptivity by promoting the transformation of endometrial epithelial cells 胎盘滋养细胞衍生的细胞外囊泡通过促进子宫内膜上皮细胞的转化来调节绵羊子宫内膜容受性。

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-10-27 DOI: 10.1016/j.repbio.2025.101091

Huijia Jin , Yujiao Guo , Yanshe Xie , Xin Xiang , Zhengguang Wang , Jizhong Xiang

The establishment of endometrial receptivity is required for successful embryo implantation during early pregnancy in many mammals. Extracellular vesicles (EVs) microRNAs (miRNAs) play an important role during embryo implantation. While their roles have been characterized in other species, the specific functions of trophoblast-derived EVs miRNAs in ovine endometrial receptivity remain undefined. In this study, we systematically investigated the effects of ovine placental trophoblast (OTR) cells-derived EVs on ovine endometrial epithelial cells (EECs) by cck-8 assay, EdU assay, cell migration assay, RT-qPCR and ultrastructural examination of apical plasma membranes. Subsequently, miRNA expression profiles of EV-treated EECs were identified and analyzed by miRNA-Seq. The results showed that OTR cells-derived EVs were taken up by EECs, enhancing the migration of EECs. EVs treatment reduced microvilli on the apical plasma membranes of EECs. The expression of genes involved in endometrial receptivity increased. OTR cells-derived EVs induced changes consistent with a receptive phenotype through coordinated cellular remodeling and gene expression changes. The miRNA-Seq results revealed 287 detectable miRNAs, including 34 with significant differential expression (20 upregulated and 14 downregulated) in EV-treated versus control EECs. The predicted target genes of these differentially expressed miRNAs were enriched in signaling pathways regulating embryo implantation and endometrial receptivity, such as MAPK, Toll-like receptor, adherens junction and focal adhesion. Our in vitro findings suggested that OTR cells-derived EVs may promote endometrial receptivity by facilitating the transformation of EECs, as indicated by receptivity-associated morphological and molecular changes. It provided novel insights for improving successful pregnancy rate in sheep.

子宫内膜容受性的建立是许多哺乳动物妊娠早期胚胎成功着床的必要条件。细胞外囊泡（EVs） microRNAs （miRNAs）在胚胎着床过程中起着重要作用。虽然它们在其他物种中的作用已被确定，但滋养细胞来源的EVs mirna在绵羊子宫内膜容受性中的具体功能仍不清楚。本研究采用cck-8法、EdU法、细胞迁移法、RT-qPCR及顶质膜超微结构检测等方法，系统研究了胎盘滋养细胞（OTR）源性ev对绵羊子宫内膜上皮细胞（EECs）的影响。随后，通过miRNA- seq鉴定和分析ev处理的EECs的miRNA表达谱。结果表明，OTR细胞衍生的电动汽车被EECs吸收，增强了EECs的迁移。EVs处理减少了EECs顶端质膜上的微绒毛。与子宫内膜容受性相关的基因表达增加。OTR细胞衍生的ev通过协调的细胞重塑和基因表达变化诱导了与受体表型一致的变化。miRNA-Seq结果显示，与对照组相比，ev处理的eec中有287种可检测到的mirna，其中34种具有显著差异表达（20种上调，14种下调）。这些差异表达的mirna的预测靶基因富集于调控胚胎着床和子宫内膜容受性的信号通路，如MAPK、toll样受体、粘附体连接和局灶粘附。我们的体外研究结果表明，OTR细胞衍生的ev可能通过促进EECs的转化来促进子宫内膜容受性，这表明了与容受性相关的形态学和分子变化。为提高绵羊妊娠成功率提供了新的见解。

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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 : 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

Moringa oleifera leaves aqueous extract mitigates nicotine-induced reproductive toxicity in male rats 辣木叶水提物减轻尼古丁诱导的雄性大鼠生殖毒性

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-10-15 DOI: 10.1016/j.repbio.2025.101093

Ahmed Mohamed Ibrahim, Ahmed Emam Dakrory, Amel Ramadan Omar , Aya A. Mahmoud

Nicotine, a chemical component included in tobacco, has been demonstrated to influence various facets of spermatogenesis and sperm functionality. Moringa oleifera Lam. (Moringaceae) is used in traditional medicine to treat various ailments, including reproductive toxicity. The current study aims to investigate the ameliorative effect of Moringa oleifera leaves aqueous extract (MOE) on nicotine (NT)-induced reproductive toxicity in male rats. Forty rats were assigned into four groups (n = 10): control (distilled water), MOE (400 mg/kg), NT (1 mg/kg), and NT + MOE groups, and orally treated for 56 days. At the end of the experiment, body and organ weights, epididymal sperm analysis, oxidative stress, hormone levels, and histopathological abnormalities were assessed. Nicotine administration results in a significant increase in malondialdehyde (MDA) levels, accompanied by a decrease in glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). Consequently, NT decreases sperm quality and serum reproductive hormone levels, including testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH), and distorts testicular tissue architecture. The oral administration of MOE caused a significant decrease in MDA concentration and an increase in the levels of antioxidant molecules (GSH, CAT, SOD) and serum reproductive hormones levels. Additionally, it improved sperm characteristics, including sperm count, motility, viability, and morphology and partial improvement to the histological architecture of the testis. Our findings imply that 400 mg/kg of Moringa oleifera leaves may be utilized to enhance reproductive parameters against NT-induced reproductive toxicity in male rats, with the primary mechanism attributed to its antioxidant properties.

尼古丁是烟草中含有的一种化学成分，已被证明可以影响精子发生和精子功能的各个方面。辣木。（辣木科）在传统医学中用于治疗各种疾病，包括生殖毒性。本研究旨在探讨辣木叶水提物（MOE）对尼古丁（NT）诱导的雄性大鼠生殖毒性的改善作用。将40只大鼠分为4组（n = 10）：对照组（蒸馏水）、MOE组（400 mg/kg）、NT组（1 mg/kg）、NT + MOE组，口服56 d。实验结束时，对大鼠的体重、脏器重量、附睾精子分析、氧化应激、激素水平和组织病理学异常进行评估。服用尼古丁会导致丙二醛（MDA）水平显著增加，同时伴有谷胱甘肽（GSH）、过氧化氢酶（CAT）和超氧化物歧化酶（SOD）的减少。因此，NT降低精子质量和血清生殖激素水平，包括睾酮、促卵泡激素（FSH）和黄体生成素（LH），并扭曲睾丸组织结构。口服MOE可显著降低MDA浓度，升高抗氧化分子（GSH、CAT、SOD）水平和血清生殖激素水平。此外，它还改善了精子特征，包括精子数量、活力、活力和形态，并部分改善了睾丸的组织学结构。我们的研究结果表明，400 mg/kg辣木叶可用于增强雄性大鼠的生殖参数，以对抗nt诱导的生殖毒性，其主要机制归因于其抗氧化特性。

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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 : 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

Testis-specific gene C3ORF22/BC048671 is dispensable for spermiogenesis and male fertility 睾丸特异性基因C3ORF22/BC048671在精子发生和男性生育中是不可或缺的

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-10-11 DOI: 10.1016/j.repbio.2025.101089

Shiyue Du , Yongfu Liu , Le Wang , Liuliu Shi , Xiaoying Zhao , Zhongcheng Yang , Wei Yuan , Xiaoying Deng , Jiahua Liu , Shenglei Feng , Rui Chen

Testicular tissue displays the most complex transcriptome across all tissues, with over 2000 genes exhibiting testis-enriched expression patterns. However, the functional ambiguity of such genes limits our understanding of spermatogenesis and male fertility. Here, we reanalyzed testicular gene expression profiles from patients with impaired spermatogenesis and identified that reduced expression of the testis-specific gene C3ORF22 was correlated with spermatogenic defects in humans. We showed that the murine ortholog BC048671 was predominant expressed in round spermatids, and its protein is present in spermatozoa. BC048671 knockout (KO) mice exhibited normal fertility, sperm morphology, and sperm motility. Intriguingly, RNA-Seq analysis revealed that BC048671 was the most markedly dysregulated gene in KO testes. Although proteomic analysis reveals the down-regulated ADAM family members (e.g., ADAM28 and ADAM2) in BC048671-null sperm, expression of the key downstream effector ADAM3 remained unaffected. These findings indicate that BC048671/C3ORF22 exhibits functional redundancy in spermatozoa. Although C3ORF22 is dispensable for male fertility, we consider it essential to report such negative results to guide researchers to prioritize efforts toward genes critical for human fertility.

睾丸组织在所有组织中表现出最复杂的转录组，有超过2000个基因表现出睾丸富集的表达模式。然而，这些基因的功能模糊限制了我们对精子发生和男性生育能力的理解。在这里，我们重新分析了精子发生受损患者的睾丸基因表达谱，发现睾丸特异性基因C3ORF22的表达减少与人类精子发生缺陷相关。我们发现小鼠同源基因BC048671在圆形精子中主要表达，其蛋白存在于精子中。BC048671基因敲除（KO）小鼠表现出正常的生育能力、精子形态和精子活力。有趣的是，RNA-Seq分析显示，BC048671是KO睾丸中最明显的失调基因。尽管蛋白质组学分析显示，在bc048671缺失的精子中，ADAM家族成员ADAM28和ADAM2下调，但关键的下游效应物ADAM3的表达未受影响。这些发现表明BC048671/C3ORF22在精子中表现出功能冗余。尽管C3ORF22在男性生育能力中是必不可少的，但我们认为报告这样的阴性结果对于指导研究人员优先考虑对人类生育能力至关重要的基因是必要的。

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引用次数: 0

Casimiroa edulis extract modulates testosterone levels, testicular enzymes and spermatogenesis disorders in streptozotocin-induced diabetic male rats 毛豆提取物对链脲佐菌素诱导的糖尿病雄性大鼠睾酮水平、睾丸酶和精子发生障碍的调节作用

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-10-11 DOI: 10.1016/j.repbio.2025.101088

Aya A. Mahmoud, Amel Ramadan Omar, Heba Ali Abd El-Rahman

Diabetes mellitus is a serious health issue that adversely affects male reproductive function and contributes to the rise in male infertility. This study examined the effectiveness of Casimiroa edulis leaf extract in improving reproductive impairment in diabetic male rats. Forty male rats were divided into control, Casimiroa edulis extract-treated, diabetic, and diabetic + Casimiroa edulis groups. Diabetic rats showed a notable reduction in sperm quality, a considerable rise in serum cholesterol levels, accompanied by a decrease in both androstenedione and testosterone levels. Histological examination of testicular tissue revealed degeneration of the seminiferous tubules, depletion of germinal cells, and lack of Leydig cells. They also exhibited a notable reduction in the activity of testicular enzymes, specifically 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase, along with a rise in the level of dehydroepiandrosterone. Casimiroa edulis treatment substantially reduced cholesterol levels, enhanced the activity of testicular enzymes, and restored testicle structure. Consequently, testosterone levels were elevated, and sperm quality was improved. To conclude, Casimiroa edulis may mitigate the negative effects of diabetes mellitus on the reproductive parameters of male rats and enhance fertility.

糖尿病是一个严重的健康问题，对男性生殖功能产生不利影响，并导致男性不育症的增加。本研究探讨了金针叶提取物对糖尿病雄性大鼠生殖功能障碍的改善作用。将40只雄性大鼠分为对照组、枫香提取物组、糖尿病组和糖尿病+ 枫香组。糖尿病大鼠表现出精子质量显著下降，血清胆固醇水平显著上升，雄烯二酮和睾丸激素水平均下降。睾丸组织的组织学检查显示精小管变性，生发细胞耗竭，间质细胞缺乏。他们还表现出睾丸酶活性的显著降低，特别是3β-羟基类固醇脱氢酶和17β-羟基类固醇脱氢酶，同时脱氢表雄酮水平升高。卡西米罗处理显著降低了胆固醇水平，提高了睾丸酶的活性，恢复了睾丸结构。结果，睾酮水平升高，精子质量得到改善。综上所述，枫香可减轻糖尿病对雄性大鼠生殖参数的负面影响，提高生殖能力。

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引用次数: 0

MicroRNA mediated downregulation of HSD17B1 impairs estrone-to-estradiol conversion in polycystic ovarian syndrome MicroRNA介导的HSD17B1下调损害多囊卵巢综合征中雌二醇与雌二醇的转化。

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-09-29 DOI: 10.1016/j.repbio.2025.101085

Prajna Bhandary , Prasanna Kumar Shetty , Praveenkumar Shetty , Lakshmi Manjeera , Prakash Patil

Polycystic ovary syndrome (PCOS) is a complicated disorder with genetic and epigenetic factors as the potential contributors of disease progression. The major findings of PCOS involves an imbalanced estrogen and androgen. The gene HSD17B1 is known to be involved in the synthesis of these steroids. Because miRNAs, which are short non-coding RNAs that regulate genes, are promising therapeutic possibilities for disease regulation, this study focused on the effect of miRNAs that target the HSD17B1 gene in PCOS. TargetScan database was used to identify the target miRNAs of HSD171B1. In-silico approaches were employed for prediction of expression levels of HSD17B1, miR-4430 and miR-200b-5p in PCOS and for the functional annotations of miRNAs. Validated the relative expression of HSD17B1, miR-4430, miR-200b-5p and HSD17B1 protein levels in the serum PCOS and control (n = 40/each group) using RT-qPCR and ELISA. Estrone (E1), and androstenedione (A4), were significantly increased and estradiol (E2) was significantly decreased in PCOS. The relative expression shows, overexpression of miR-4430, miR-200b-5p and reduced expression of HSD17B1 gene as well as lower HSD17B1 protein level in PCOS. The in-silico functional annotation indicated that these miRNAs are involved pathways related to PCOS pathogenesis such as steroid synthesis and cell proliferation. Additionally, the diagnostic effectiveness by ROC analysis shows AUC for HSD17B1, miR-4430 and miR-200b-5p is 0.874, 0.869, and 0.943 respectively, reflecting a good diagnostic biomarker for PCOS. In conclusion, study indicates that overexpressed miR-4430 and miR-200b-5p probably limits the synthesis of estrone to estradiol via HSD17B1 in PCOS.

多囊卵巢综合征（PCOS）是一种复杂的疾病，遗传和表观遗传因素是疾病进展的潜在因素。多囊卵巢综合征的主要表现包括雌激素和雄激素失衡。已知基因HSD17B1参与了这些类固醇的合成。由于miRNAs是一种短的非编码rna，可以调节基因，在疾病调节方面具有很好的治疗前景，因此本研究主要关注靶向HSD17B1基因的miRNAs在PCOS中的作用。使用TargetScan数据库鉴定HSD171B1的靶mirna。采用芯片方法预测PCOS中HSD17B1、miR-4430和miR-200b-5p的表达水平，并对mirna进行功能注释。采用RT-qPCR和ELISA验证血清PCOS和对照组中HSD17B1、miR-4430、miR-200b-5p和HSD17B1蛋白的相对表达水平（n = 40/每组）。PCOS患者雌二醇（E1）和雄烯二酮（A4）水平显著升高，雌二醇（E2）水平显著降低。相对表达结果显示，PCOS中miR-4430、miR-200b-5p过表达，HSD17B1基因表达降低，HSD17B1蛋白水平降低。计算机功能注释表明，这些mirna参与了PCOS发病机制的类固醇合成和细胞增殖等相关途径。此外，ROC分析显示HSD17B1、miR-4430和miR-200b-5p的AUC分别为0.874、0.869和0.943，是PCOS较好的诊断生物标志物。总之，研究表明，在PCOS中，过表达的miR-4430和miR-200b-5p可能通过HSD17B1限制了雌酮合成为雌二醇。

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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 : 2025-09-27 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。

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引用次数: 0

Protective effect of nicotinamide mononucleotide against soybean isoflavone induced damage in mouse testis 烟酰胺单核苷酸对大豆异黄酮致小鼠睾丸损伤的保护作用。

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-09-27 DOI: 10.1016/j.repbio.2025.101080

Kaixuan Wang , Haiwei He , Yadan Jin , Fangdi Zhang , Ruixue Ma , Fei Wang , Baohua Li , Guoliang Zhang

Soybean isoflavone (SI) was one type of phytoestrogen that competitively interacts with estrogen in the body, potentially interfering with endocrine balance, spermatogenesis, and the normal function of testicular cells. Nicotinamide mononucleotide (NMN), an important bioactive substance, enhances organ and tissue function through mechanisms such as reducing oxidative stress. However, limited information exists regarding the ability of NMN to improve phytoestrogen-induced damage to testis development in mice. The study investigated the protective effect of NMN on testicular damage in mice caused by SI. The results of this study revealed SI-treated mice exhibited a significant reduction in body weight, testicular index, and reproduction-related factors, as well as a marked increase in apoptosis. RNA sequencing (RNA-seq) results demonstrated that exposure to SI led to the enrichment of differentially expressed genes (DEGs) primarily in cellular autophagy and proliferation pathways within mouse testicular tissues. Administration of SI at doses of 200 mg/kg and 400 mg/kg downregulated the Rb1cc1 gene in the longevity-regulating pathway and the Vav2 gene in the cAMP signaling pathway in mouse testes. In contrast, treatment with 100 mg/kg NMN significantly alleviated the adverse effects induced by SI. In summary, NMN exhibited significant therapeutic potential in alleviating SI-induced testicular damage.

大豆异黄酮（Soybean isoflavone， SI）是一种与体内雌激素竞争性相互作用的植物雌激素，可能干扰内分泌平衡、精子发生和睾丸细胞的正常功能。烟酰胺单核苷酸（Nicotinamide mononucleotide， NMN）是一种重要的生物活性物质，可通过降低氧化应激等机制增强器官和组织功能。然而，关于NMN改善植物雌激素诱导的小鼠睾丸发育损伤的能力的信息有限。研究NMN对SI致小鼠睾丸损伤的保护作用。本研究结果显示，si处理小鼠的体重、睾丸指数和生殖相关因子显著降低，细胞凋亡明显增加。RNA测序（RNA-seq）结果表明，暴露于SI导致小鼠睾丸组织中主要在细胞自噬和增殖途径中差异表达基因（DEGs）的富集。200 mg/kg和400 mg/kg剂量的SI可下调小鼠睾丸长寿调节通路中的Rb1cc1基因和cAMP信号通路中的Vav2基因。相比之下，100 mg/kg NMN处理显著减轻了SI引起的不良反应。综上所述，NMN在减轻si诱导的睾丸损伤方面表现出显著的治疗潜力。

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引用次数: 0

Tannic acid protection against oxidative and inflammatory effects of monosodium glutamate on testis: Molecular and biochemical approach 单宁酸对谷氨酸钠对睾丸氧化和炎症的保护作用：分子和生化方法

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-09-27 DOI: 10.1016/j.repbio.2025.101077

Sümeyye Çınar Özkan, Emine Toraman

In this study, the toxic effects of monosodium glutamate (MSG), a widely used food additive, on rat testicular tissue were evaluated and the potential protective role of tannic acid (TA), a natural polyphenolic compound, against this toxicity was investigated. For this purpose, 24 rats were divided into four groups (n=6). They were administered 2 g/kg monosodium glutamate (MSG) for 21 days. Subsequently, they were treated with 50 mg/kg tannic acid (TA). At the end of this period, testicular tissues were collected for molecular and biochemical analyses. Antioxidant enzyme activities (SOD, CAT, GPx, GST, GR), oxidative stress markers (GSH, MDA), inflammatory markers (TNF-α, iNOS, COX-2) and DNA damage indicator 8-OHdG (8-hydroxy-2′-deoxyguanosine) levels were analyzed in the experimental groups. In addition, expression levels of antioxidant defense (Sod, Cat, Gpx, Gst, Gr), inflammation (Tnf-α, Il-6, Nf-κB, Cox-2, Inos, Foxo1, Foxo3) and reproductive function-related genes (Dazl, Ddx4, Amh) were evaluated by qPCR. In the MSG group, a decrease in GSH level and a significant increase in MDA, TNF-α, iNOS and 8-OHdG levels were found (P<0.01). While a decrease was observed in SOD, CAT, GST and GR enzyme activities (P<0.01), no significant change was found in GPx activity. At the gene level, MSG administration suppressed the expression of genes related to antioxidant and germ cell functions and increased the expression of Tnf-α, lL-6, Cox-2 and Foxo3 (P<0.001). On the other hand, TA, both alone and in combination with MSG, demonstrated ameliorative effects on inflammation and oxidative stress, although not on all parameters. The data suggest that MSG induces oxidative stress, inflammation, DNA damage, and impaired germ cell function in testicular tissue. It was concluded that TA treatment suppresses these harmful effects, supports cellular defenses, and may help preserve testicular function.

本研究评估了广泛使用的食品添加剂味精（MSG）对大鼠睾丸组织的毒性作用，并研究了天然多酚类化合物单宁酸（TA）对这种毒性的潜在保护作用。为此，将24只大鼠分为4组（n=6）。2 g/kg谷氨酸钠（MSG）治疗21 d。随后给予50 mg/kg单宁酸（TA）处理。在这一时期结束时，收集睾丸组织进行分子和生化分析。分析各组抗氧化酶活性（SOD、CAT、GPx、GST、GR）、氧化应激标志物（GSH、MDA）、炎症标志物（TNF-α、iNOS、COX-2）和DNA损伤指标8-OHdG（8-羟基-2′-脱氧鸟苷）水平。此外，采用qPCR检测抗氧化防御（Sod、Cat、Gpx、Gst、Gr）、炎症（Tnf-α、Il-6、Nf-κB、Cox-2、Inos、Foxo1、Foxo3）和生殖功能相关基因（Dazl、Ddx4、Amh）的表达水平。味精组GSH水平降低，MDA、TNF-α、iNOS和8-OHdG水平显著升高（P<0.01）。SOD、CAT、GST和GR酶活性降低（P<0.01）， GPx活性无显著变化。在基因水平上，味精抑制了与抗氧化和生殖细胞功能相关基因的表达，增加了Tnf-α、lL-6、Cox-2和Foxo3的表达（P<0.001）。另一方面，TA单独使用和与味精联合使用均显示出对炎症和氧化应激的改善作用，尽管并非对所有参数都有改善作用。这些数据表明，味精可诱导睾丸组织的氧化应激、炎症、DNA损伤和生殖细胞功能受损。由此得出结论，TA治疗可以抑制这些有害影响，支持细胞防御，并可能有助于保持睾丸功能。

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引用次数: 0