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Exosomal ncRNAs in seminal fluid: Unraveling their regulatory roles in male infertility 精液外泌体ncRNAs:揭示其在男性不育中的调节作用
IF 2.5 3区 生物学 Q3 REPRODUCTIVE BIOLOGY Pub Date : 2025-12-31 DOI: 10.1016/j.repbio.2025.101175
Marwah Suliman Maashi
By transmitting bioactive substances, including proteins, lipids, and a varied spectrum of non-coding RNAs, seminal exosomes—including epididymosomes and prostasomes—are shown to be crucial in sperm maturation, motility, and protection. The paper emphasizes how miRNAs, lncRNAs, and circRNAs within these exosomes affect gene expression during spermatogenesis and are starting to be interesting non-invasive biomarkers for several infertility abnormalities, including azoospermia and asthenozoospermia. It also addresses the therapeutic possibilities of exosome-based approaches in reducing inflammation, oxidative stress, and cellular damage in the male reproductive system. The paper identifies essential information gaps and suggests future research paths to clarify the molecular processes behind male infertility by combining knowledge from proteomic, lipidomic, and transcriptomic investigations. These results help to close the knowledge gap on seminal exosomes and open the door for creative therapeutic and diagnostic tools in reproductive medicine.
通过传递生物活性物质,包括蛋白质、脂质和各种非编码rna,精子外泌体(包括附睾和前列腺体)在精子成熟、运动和保护中起着至关重要的作用。本文强调了这些外泌体中的miRNAs、lncRNAs和circRNAs如何影响精子发生过程中的基因表达,并开始成为几种不孕症异常(包括无精子症和弱精子症)的有趣的非侵入性生物标志物。它还解决了基于外泌体的治疗方法在减少炎症、氧化应激和男性生殖系统细胞损伤方面的可能性。本文确定了必要的信息缺口,并提出了未来的研究路径,以阐明男性不育背后的分子过程,通过结合蛋白质组学,脂质组学和转录组学研究的知识。这些结果有助于缩小对精液外泌体的知识差距,并为生殖医学的创造性治疗和诊断工具打开大门。
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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 Pub 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
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 Pub 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
Reproductive biology characterization of violinha Loricariichthys anus 喉喉小提琴的生殖生物学特征
IF 2.5 3区 生物学 Q3 REPRODUCTIVE BIOLOGY Pub Date : 2025-12-20 DOI: 10.1016/j.repbio.2025.101171
Douglas C. Selle , Raquel S. dos Santos , Thaiza R. de Freitas , Jhony L. Benato , Thales de S. França , Renata V. Dantas , Marco A. Rotta , Marcelle F.O. Barbosa , Vanessa Coimbra , Diógenes H. Siqueira-Silva , Danilo P. Streit Jr.
This study aimed to characterize the reproductive biology of Loricariichthys anus (violinha) from the Guaíba River (Brazil) to support conservation efforts and development of captive reproduction protocols. Monthly collections (November 2021-October 2022) of 144 specimens were analyzed for sexual dimorphism, gonadosomatic index (GSI), gonadal histology, and sperm parameters (motility, concentration, morphology). Sexual dimorphism was evidenced by elongated lower lip in males, predominantly during the reproductive period (November-March). GSI values peaked during November-March for both sexes (P < 0.05). Histological analysis revealed females reached maturity from November to February with evidence of multiple spawning, while males produced sperm year-round, albeit in low volumes. Sperm motility parameters differed significantly between individuals (P < 0.05) with mean concentration of 6.88 × 106 ± 8.18 × 105 spermatozoa/mL. L. anus reproductive period occurs from November to February, with males presenting low seminal volume and viable sperm concentration compared to other Loricariidae species, which has implications for both conservation and captive reproduction efforts.
本研究旨在研究巴西Guaíba河Loricariichthys anus (violinha)的生殖生物学特征,以支持圈养繁殖方案的制定和保护工作。对每月采集的144例标本(2021年11月至2022年10月)进行两性二态性、性腺指数(GSI)、性腺组织学和精子参数(活力、浓度、形态)的分析。雌雄二态性表现为雄性下唇拉长,主要发生在生殖期(11 - 3月)。GSI值在11月至3月期间达到峰值(P <; 0.05)。组织学分析显示,雌性从11月到2月达到成熟,有证据表明多次产卵,而雄性全年产生精子,尽管数量较少。精子活力指标个体间差异显著(P <; 0.05),平均浓度为6.88 × 106 ± 8.18 × 105个精子/mL。在11月至次年2月的生殖期,与其他蠓科物种相比,雄性蠓的精液量和存活精子浓度较低,这对保护和圈养繁殖具有重要意义。
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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 Pub 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。
{"title":"Biochemical profile of fetal fluids in alpacas (Vicugna pacos) during pregnancy and immediate postpartum","authors":"Joel Iván Pacheco ,&nbsp;Hugo Wenceslao Deza ,&nbsp;Víctor Manuel Vélez-Marroquín ,&nbsp;Wilber García ,&nbsp;Francisco Franco ,&nbsp;Edward H. Cabezas-Garcia ,&nbsp;Daniel Marcelo Lombardo","doi":"10.1016/j.repbio.2025.101172","DOIUrl":"10.1016/j.repbio.2025.101172","url":null,"abstract":"<div><div>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 (<em>Vicugna pacos</em>). 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.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"26 1","pages":"Article 101172"},"PeriodicalIF":2.5,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786494","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
Correlation between Polycomb repressive complex proteins and epithelial–mesenchymal transition-associated genes in endometriotic tissues 子宫内膜异位症组织中Polycomb抑制复合体蛋白与上皮-间充质过渡相关基因的相关性
IF 2.5 3区 生物学 Q3 REPRODUCTIVE BIOLOGY Pub Date : 2025-12-19 DOI: 10.1016/j.repbio.2025.101173
Anushree Nandan , Abhishek Mangeshikar , Vaijayanti Kale , Anuradha Vaidya , Prasad Pethe
Endometriosis is a condition in which functional endometrial glands and stroma are found to grow outside the uterine cavity that can lead to symptoms like dysmenorrhea, dyspareunia, adhesions, and infertility. Current treatment strategies can provide only symptomatic relief as its etiology remains unclear. Several studies have linked the cellular process of epithelial–mesenchymal transition (EMT) to endometriosis development; however, what triggers EMT states in endometriosis is unknown. Polycomb group (PcG) proteins are histone modifiers that control gene expression by catalyzing repressive histone modifications such as H3K27me3/2 and H2AK119ub1. The misexpression of PcGs and/or genes controlled by them reportedly causes several types of cancers, such as breast, colon, pancreatic, and liver. We investigated whether dysregulation of PcG proteins such as RING1B, BMI1, and EZH2 in ectopic endometriotic tissue as compared to eutopic correlates with genes required for EMT in endometriotic tissue from the same patient with laparoscopically confirmed endometriosis. We quantified the expression of Polycomb repressive complex 1 (PRC1) genes (RING1B and BMI1), EMT-associated genes (TWIST, SNAI1, SNAI2, ZEB1, CDH1, CDH2, and VIM) in paired eutopic and ectopic (endometriotic) tissue samples obtained from 12 women who underwent laparoscopy for severe endometriosis identified as per #ENZIAN classification. Our results showed that the endometriotic lesions had higher gene expression of PRC1 proteins – RING1B and BMI1 as well as higher expression of EMT associated genes than the endometrial tissue. Thus, our results suggest that PRC1 proteins may have a role in the pathogenesis of endometriosis.
子宫内膜异位症是一种功能正常的子宫内膜腺体和间质生长在子宫腔外的情况,可导致痛经、性交困难、粘连和不孕等症状。目前的治疗策略只能提供症状缓解,因为其病因尚不清楚。一些研究将上皮-间质转化(EMT)的细胞过程与子宫内膜异位症的发展联系起来;然而,是什么触发了子宫内膜异位症的EMT状态尚不清楚。Polycomb group (PcG)蛋白是组蛋白修饰因子,通过催化抑制组蛋白修饰如H3K27me3/2和H2AK119ub1来控制基因表达。据报道,PcGs和/或由PcGs控制的基因的错误表达会导致几种类型的癌症,如乳腺癌、结肠癌、胰腺癌和肝癌。我们研究了与异位子宫内膜异位症患者相比,异位子宫内膜异位症组织中PcG蛋白如RING1B、BMI1和EZH2的失调是否与子宫内膜异位症组织中EMT所需的基因相关。我们量化了从12名因严重子宫内膜异位症接受腹腔镜检查的妇女中获得的配对异位和异位(子宫内膜异位症)组织样本中Polycomb抑制复合体1 (PRC1)基因(RING1B和BMI1)、emt相关基因(TWIST、SNAI1、SNAI2、ZEB1、CDH1、CDH2和VIM)的表达。我们的研究结果表明,与子宫内膜组织相比,子宫内膜异位症病变中PRC1蛋白- RING1B和BMI1基因表达较高,EMT相关基因表达较高。因此,我们的研究结果表明PRC1蛋白可能在子宫内膜异位症的发病机制中起作用。
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引用次数: 0
Origin, viability, and cell cycle status of seminal somatic cells for potential application in cattle cloning via nuclear transfer 牛核移植克隆中潜在应用的精体细胞的起源、活力和细胞周期状态。
IF 2.5 3区 生物学 Q3 REPRODUCTIVE BIOLOGY Pub Date : 2025-12-17 DOI: 10.1016/j.repbio.2025.101170
Higor da Silva Ferreira , Gabriella Borba de Oliveira , Eduardo de Oliveira Sanguinet , Ana Laura da Silva Feijó , César Augusto Pinzón-Osorio , Verônica Rafaela Benvenutti , Louise Fontoura Köhler , Marianna Bertolini , Fernando Almeida-Souza , Felipe de Jesus Moraes Junior , David Driemeier , Ana Lúcia Abreu-Silva , José Luiz Rigo Rodrigues , Marcelo Bertolini
Seminal somatic cells (SSCs) represent promising donor nuclei for cloning by somatic cell nuclear transfer (SCNT), particularly for genetic conservation. This study aimed to identify and characterize SSCs present in bovine semen, determine their possible tissue origins, and evaluate their suitability for cloning. SSCs were isolated using sucrose or mini-Percoll® density gradients and analyzed for morphology, viability, and cell cycle status, as well as their potential use in SCNT cloning. Cytological and histological assessments of the bovine genitourinary tract were performed side-by-side to identify the anatomical origins of each SSC type, and epithelial marker expression was examined by RT-qPCR in SSCs, urethral, and bladder tissues. The mini-Percoll® gradient efficiently separated SSCs from sperm cells, concentrating viable somatic cells in the 20 % fraction. Three SSC types were identified (polygonal, round, and elongated), with polygonal cells being the most abundant and highly viable (>90 %), although they failed to adhere or proliferate in culture. Flow cytometry revealed that most polygonal SSCs (89 %) were arrested at the G0/G1 phase, indicating cell-cycle compatibility for cloning, although with low membrane fusion capacity in SCNT assays. Cytological, histological, and molecular findings collectively indicate that polygonal SSCs most likely originate from the non-keratinized stratified epithelium of the urethral navicular fossa, whereas round and elongated SSCs may derive from the proximal urethra and the ampullary-vesicular-ductal complex, respectively. These results provide a comprehensive anatomical and molecular characterization of SSC subtypes in bovine semen, offering a foundation for improving SCNT cloning standardization and applications in genetic preservation.
在体细胞核移植(SCNT)技术中,生殖体细胞(ssc)是一种很有前途的供核,尤其在遗传保护方面。本研究旨在鉴定牛精液中存在的ssc,确定其可能的组织来源,并评估其克隆的适用性。使用蔗糖或mini-Percoll®密度梯度分离ssc,分析其形态、活力和细胞周期状态,以及它们在SCNT克隆中的潜在应用。同时对牛生殖泌尿道进行细胞学和组织学评估,以确定每种SSC类型的解剖学起源,并通过RT-qPCR检测SSC、尿道和膀胱组织中上皮标志物的表达。mini-Percoll®梯度有效地从精子细胞中分离ssc,浓缩20% %的活体细胞。鉴定出三种SSC类型(多边形、圆形和细长型),其中多边形细胞最丰富,存活率最高(bbb90 %),尽管它们在培养中不能粘附或增殖。流式细胞术显示,大多数多边形SSCs(89 %)停留在G0/G1期,表明细胞周期兼容性克隆,尽管在SCNT检测中膜融合能力较低。细胞学、组织学和分子检查结果共同表明,多边形SSCs最有可能起源于尿道舟窝的非角化层状上皮,而圆形和细长的SSCs可能分别来自尿道近端和壶腹-膀胱-导管复合体。这些结果为牛精液中SSC亚型的解剖和分子特征提供了全面的分析,为提高SCNT的克隆标准化和遗传保存应用奠定了基础。
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引用次数: 0
Mechanisms underlying Sorghum bicolor extract protection against monosodium glutamate-induced reproductive toxicity in female rats 高粱双色提取物对谷氨酸钠诱导的雌性大鼠生殖毒性的保护机制。
IF 2.5 3区 生物学 Q3 REPRODUCTIVE BIOLOGY Pub Date : 2025-12-03 DOI: 10.1016/j.repbio.2025.101168
Dumebi Anita Konwea , Jerome Ndudi Asiwe , Julian Enwerim Nwangwa , Blessing Zeinab Odili-Ovili , Saviour God’swealth Usin , Eze Kingsley Nwangwa
Monosodium glutamate (MSG) has been implicated in female reproductive toxicity through endocrine disruption, oxidative stress, inflammation, and apoptosis. This study investigated the protective role of Sorghum bicolor extract (SBE), a polyphenol-rich nutraceutical, against MSG-induced reproductive dysfunction in female Wistar rats, integrating in vivo outcomes with in silico docking analysis. Rats were exposed to MSG (4 g/kg) with or without SBE supplementation (100 mg/kg) orally for 28 days. Estrous cycle, sexual behaviors, hormonal profiles, oxidative and nitrosative stress markers, inflammatory mediators, and apoptotic regulators were assessed. Molecular docking evaluated the interactions of SBE phytochemicals with LHB and LHCGR. MSG disrupted the pituitary–gonadal axis, shortened estrous phases, suppressed reproductive behaviors, increased lipid peroxidation, activated NF-κB, and triggered mitochondrial apoptosis. SBE restored gonadotropins and steroid hormones, normalized estrous cycle, enhanced antioxidant defenses, suppressed inflammation, and prevented apoptosis. Docking analysis revealed strong ligand–protein interactions, supporting endocrine and cellular protection. Conclusively, SBE confers robust gonadoprotective effects against MSG toxicity through endocrine restoration, antioxidant, anti-inflammatory, and anti-apoptotic mechanisms validated in vivo and in silico.
味精(MSG)通过内分泌干扰、氧化应激、炎症和细胞凋亡与女性生殖毒性有关。本研究结合体内结果和硅对接分析,研究了富含多酚的营养制剂高粱双色提取物(SBE)对味精诱导的雌性Wistar大鼠生殖功能障碍的保护作用。大鼠口服味精(4 g/kg),并添加或不添加SBE(100 mg/kg),持续28天。评估发情周期、性行为、激素谱、氧化和亚硝化应激标志物、炎症介质和凋亡调节因子。分子对接研究了SBE植物化学物质与LHB和LHCGR的相互作用。味精破坏垂体-性腺轴,缩短发情期,抑制生殖行为,增加脂质过氧化,激活NF-κB,引发线粒体凋亡。SBE恢复促性腺激素和类固醇激素,使发情周期正常化,增强抗氧化防御,抑制炎症,防止细胞凋亡。对接分析显示配体-蛋白相互作用强,支持内分泌和细胞保护。综上所述,SBE通过内分泌恢复、抗氧化、抗炎和抗凋亡机制对味精毒性具有强大的促性腺保护作用。
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引用次数: 0
Inhibitory role of activin A during luteinization of follicular and lutein granulosa cells from small antral and preovulatory human follicles 激活素A在卵泡黄体化和卵泡叶黄素颗粒细胞中的抑制作用。
IF 2.5 3区 生物学 Q3 REPRODUCTIVE BIOLOGY Pub Date : 2025-11-29 DOI: 10.1016/j.repbio.2025.101169
Lea Bejstrup Jensen , Laura Victoria Højer , Lisette Schönhage , Cristina Subiran Adrados , Jane Alrø Bøtkjær , Tanni Borgbo , Jesús Cadenas , Kirsten Tryde Macklon , Stine Ringholm , Anette Tønnes Pedersen , Stine Gry Kristensen
Luteinization is a vital process in female reproduction, where granulosa cells differentiate into progesterone-secreting luteal cells. While luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are established promoters of luteinization, the regulatory role of activin A remains incompletely understood. This study aimed to investigate whether activin A can prevent or reverse luteinization in granulosa cells from small antral and preovulatory follicles using an in vitro model. Granulosa cells were collected from women undergoing either IVF treatment or ovarian tissue cryopreservation. Cells were cultured for 48 h with FSH, hCG, or activin A. Hormone secretion (progesterone and estradiol) and content of steroidogenic markers (CYP19A1, STAR, 17βHSD1, 3βHSD2, FSHR, and LHCGR) were analyzed via ELISA, RT-qPCR, and Western blot.

Results

demonstrated that activin A suppressed luteinization markers and progesterone production while promoting estrogen synthesis and maintaining granulosa cell features. Conversely, hCG increased luteinization marker expression and progesterone secretion, consistent with its known role in luteal transformation. Notably, granulosa cells from small antral follicles showed a distinct, stage-specific response to activin A compared to those from preovulatory follicles, indicating a temporal regulation of luteinization competence.
These findings support a regulatory role for activin A in maintaining granulosa cell identity and delaying luteinization. Understanding the differential responsiveness of granulosa cells across follicular development stages may inform new therapeutic approaches for luteal phase deficiencies and fertility preservation strategies.
黄体生成是女性生殖过程中一个重要的过程,其中颗粒细胞分化为分泌黄体激素的黄体细胞。虽然黄体生成素(LH)和人绒毛膜促性腺激素(hCG)是已知的黄体生成素的促进因子,但活化素A的调节作用仍不完全清楚。本研究旨在通过体外模型研究激活素A是否能阻止或逆转小窦卵泡和排卵前卵泡颗粒细胞的黄体生成化。颗粒细胞从接受体外受精治疗或卵巢组织冷冻保存的妇女中收集。用FSH、hCG或activin a培养细胞48 h,通过ELISA、RT-qPCR和Western blot分析激素分泌(孕酮和雌二醇)和激素生成标志物(CYP19A1、STAR、17βHSD1、3βHSD2、FSHR和LHCGR)的含量。结果:激活素A抑制黄体生成素标记物和黄体酮的产生,同时促进雌激素合成,维持颗粒细胞特征。相反,hCG增加了黄体生成素标记物的表达和黄体酮的分泌,这与它在黄体转化中的已知作用一致。值得注意的是,与来自排卵前卵泡的颗粒细胞相比,来自小腔卵泡的颗粒细胞对激活素a表现出明显的阶段特异性反应,表明黄体生成素能力的时间调节。这些发现支持激活素a在维持颗粒细胞身份和延缓黄体生成中的调节作用。了解颗粒细胞在卵泡发育阶段的不同反应性可能为黄体期缺陷和生育保护策略提供新的治疗方法。
{"title":"Inhibitory role of activin A during luteinization of follicular and lutein granulosa cells from small antral and preovulatory human follicles","authors":"Lea Bejstrup Jensen ,&nbsp;Laura Victoria Højer ,&nbsp;Lisette Schönhage ,&nbsp;Cristina Subiran Adrados ,&nbsp;Jane Alrø Bøtkjær ,&nbsp;Tanni Borgbo ,&nbsp;Jesús Cadenas ,&nbsp;Kirsten Tryde Macklon ,&nbsp;Stine Ringholm ,&nbsp;Anette Tønnes Pedersen ,&nbsp;Stine Gry Kristensen","doi":"10.1016/j.repbio.2025.101169","DOIUrl":"10.1016/j.repbio.2025.101169","url":null,"abstract":"<div><div>Luteinization is a vital process in female reproduction, where granulosa cells differentiate into progesterone-secreting luteal cells. While luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are established promoters of luteinization, the regulatory role of activin A remains incompletely understood. This study aimed to investigate whether activin A can prevent or reverse luteinization in granulosa cells from small antral and preovulatory follicles using an in vitro model. Granulosa cells were collected from women undergoing either IVF treatment or ovarian tissue cryopreservation. Cells were cultured for 48 h with FSH, hCG, or activin A. Hormone secretion (progesterone and estradiol) and content of steroidogenic markers (CYP19A1, STAR, 17βHSD1, 3βHSD2, FSHR, and LHCGR) were analyzed via ELISA, RT-qPCR, and Western blot.</div></div><div><h3>Results</h3><div>demonstrated that activin A suppressed luteinization markers and progesterone production while promoting estrogen synthesis and maintaining granulosa cell features. Conversely, hCG increased luteinization marker expression and progesterone secretion, consistent with its known role in luteal transformation. Notably, granulosa cells from small antral follicles showed a distinct, stage-specific response to activin A compared to those from preovulatory follicles, indicating a temporal regulation of luteinization competence.</div><div>These findings support a regulatory role for activin A in maintaining granulosa cell identity and delaying luteinization. Understanding the differential responsiveness of granulosa cells across follicular development stages may inform new therapeutic approaches for luteal phase deficiencies and fertility preservation strategies.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"26 1","pages":"Article 101169"},"PeriodicalIF":2.5,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145650690","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
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 Pub 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(
{"title":"Downregulation of intracellular ATP levels by PANX1 inhibits ovarian granulosa cell proliferation and mediates follicular dysplasia in elderly women","authors":"Zhiqin Zhang ,&nbsp;Xuechen Sun ,&nbsp;Xin Li ,&nbsp;Peipei Liu ,&nbsp;Liyun Cao ,&nbsp;Shenggen Long ,&nbsp;Jun Tan","doi":"10.1016/j.repbio.2025.101105","DOIUrl":"10.1016/j.repbio.2025.101105","url":null,"abstract":"<div><div>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 (&lt;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.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"26 1","pages":"Article 101105"},"PeriodicalIF":2.5,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145650664","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
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Reproductive biology
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