Reproductive biology最新文献_第4页

USP13 exacerbates the malignant progression of cervical cancer by inhibiting ECT2 ubiquitination and degradation USP13通过抑制ECT2泛素化和降解而加剧宫颈癌的恶性进展。

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-11-11 DOI: 10.1016/j.repbio.2025.101095

Tingting Li , Xiulan Xiong , Tingting Xie , Wei Liu , Xuqin Feng , Silin Chen , Xin Hu , Rengui Li , Kaiwen Fu

Cervical cancer (CC) is one of the most common malignant tumors affecting the female reproductive system. Epithelial Cell Transforming Sequence 2 (ECT2), a guanine nucleotide exchange factor, is crucial in regulating cellular functions. This study focuses on elucidating the role of ECT2 in CC and the involved underlying mechanisms. Western blot verified protein expression in tissues and cells. Cell proliferation, migration, and invasion were assessed via clone formation, wound healing, and transwell assays. Glycolytic indicators (glucose uptake, lactate release, ATP levels, lactate dehydrogenase (LDH) activity, and pyruvate dehydrogenase (PDH) activity) were detected using specific kits. UbiBrowser was used to predict ubiquitin-specific protease 13 (USP13)-mediated ECT2 deubiquitination. Co-immunoprecipitation (Co-IP) was performed to validate USP13’s deubiquitination on ECT2 and their interaction. In vivo validation employed a mouse xenograft model, with immunohistochemistry (IHC) assessing gene expression therein. This study demonstrated that ECT2 was upregulated in CC tissues and cells, and its downregulation effectively inhibited the proliferation, migration, invasion, and glycolysis of CC cells. USP13 exhibited high expression levels in CC and stabilized ECT2 expression through its deubiquitinating activity. Knockdown of USP13 significantly suppressed the malignant phenotypes of CC cells; however, this suppressive effect was markedly reversed upon ECT2 overexpression. In vivo experiments revealed that USP13 knockdown suppressed CC tumor growth by modulating ECT2 expression. Together, USP13 exacerbates the malignant progression of CC by inhibiting ECT2 ubiquitination, suggesting that targeting the USP13-ECT2 axis might be a potential therapeutic strategy for CC with notable clinical significance.

宫颈癌（CC）是影响女性生殖系统最常见的恶性肿瘤之一。上皮细胞转化序列2 （ECT2）是一种鸟嘌呤核苷酸交换因子，在调节细胞功能中起着至关重要的作用。本研究的重点是阐明ECT2在CC中的作用及其潜在机制。Western blot证实蛋白在组织和细胞中的表达。通过克隆形成、伤口愈合和transwell试验评估细胞增殖、迁移和侵袭。使用特异性试剂盒检测糖酵解指标（葡萄糖摄取、乳酸释放、ATP水平、乳酸脱氢酶（LDH）活性和丙酮酸脱氢酶（PDH）活性）。UbiBrowser用于预测泛素特异性蛋白酶13 （USP13）介导的ECT2去泛素化。采用免疫共沉淀法（Co-IP）验证USP13对ECT2的去泛素化作用及其相互作用。体内验证采用小鼠异种移植模型，免疫组织化学（IHC）评估其中的基因表达。本研究表明，ECT2在CC组织和细胞中表达上调，其下调可有效抑制CC细胞的增殖、迁移、侵袭和糖酵解。USP13在CC中表现出高表达水平，并通过其去泛素化活性稳定了ECT2的表达。敲低USP13可显著抑制CC细胞的恶性表型；然而，这种抑制作用在ECT2过表达时明显逆转。体内实验表明，USP13敲低通过调节ECT2的表达抑制CC肿瘤的生长。综上所述，USP13通过抑制ECT2泛素化而加剧CC的恶性进展，提示靶向USP13-ECT2轴可能是一种具有显著临床意义的CC潜在治疗策略。

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引用次数: 0

Influence of different cell passage numbers on bovine cloned embryo: A systematic review and meta-analysis 不同细胞传代数对牛克隆胚胎的影响：系统综述和荟萃分析

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-11-01 DOI: 10.1016/j.repbio.2025.101097

Haris Setiawan , Agung Irawan

Animal cloning remains inefficient, with live birth rates below 5 % in most mammalian species, slightly higher in bovines (20–25 %). Among various factors, nuclear donor cells play crucial roles, and their passage numbers may influence cloning efficiency. However, a definitive association between passage numbers and outcomes in cloning remains inconclusive due to insufficient data and inconsistent results. In the present meta-analytical study, we compared research using high (>6) and low (≤6) cell passage numbers across various types, breeds, and sexes of donor cells to assess their impact on embryo development and associated gene expressions in bovine clones. Our findings revealed that cell passaging influences developmental competence at the cleavage and blastocyst rates, with lower passage numbers yielding better results. Higher acetylation of H3K9 in low-passage cells is consistently associated with improved developmental competence through the blastocyst stage, although the difference was not statistically significant. Donor cells with higher histone acetylation may undergo reprogramming more easily and completely, thus improving cloning efficiency. Further analysis elucidated that the types and breeds of donor cells also affected the blastocyst outcome. Nevertheless, high heterogeneity and meta-bias were identified in the meta-analytical outcomes, particularly in cleavage, 2-cell, 8-cell, blastocyst, the total cell number (TCN), the ratio of inner cell mass and total cell number (ICM/TCN), NANOG, and birth rate, which may contribute to inconsistencies in embryo quality results and hinder comparisons between development-related gene expressions and the embryo transfer outcome.

动物克隆仍然效率低下，大多数哺乳动物物种的活产率低于5 %，牛的活产率略高（20-25 %）。在众多因素中，核供细胞起着至关重要的作用，其传代数可能影响克隆效率。然而，由于数据不足和结果不一致，传代数与克隆结果之间的明确关联仍然不确定。在当前的meta分析研究中，我们比较了不同类型、品种和性别的供体细胞使用高（>6）和低（≤6）细胞传代数的研究，以评估它们对牛克隆胚胎发育和相关基因表达的影响。我们的研究结果表明，细胞传代影响卵裂率和囊胚率的发育能力，传代次数越少，结果越好。低传代细胞中较高的H3K9乙酰化始终与囊胚期发育能力的提高相关，尽管差异无统计学意义。组蛋白乙酰化程度高的供体细胞更容易完全重编程，从而提高克隆效率。进一步的分析表明，供体细胞的类型和品种也影响囊胚的结局。然而，在meta分析结果中发现了高度异质性和meta偏倚，特别是在卵裂、2细胞、8细胞、囊胚、总细胞数（TCN）、内细胞质量与总细胞数之比（ICM/TCN）、NANOG和出生率方面，这可能会导致胚胎质量结果的不一致，并阻碍发育相关基因表达与胚胎移植结果之间的比较。

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引用次数: 0

Branched chain amino acid sufficiency is necessary for proper luteinizing hormone response and testosterone synthesis 支链氨基酸充足是促黄体激素反应和睾酮合成的必要条件

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-10-31 DOI: 10.1016/j.repbio.2025.101094

Yeva Shamailova , Saad A. Farooq , Megan E. Gilmore , Timothy J. Stanek , Esther M. Lopez , Berish B. Wetstein , Emily T. Mirek , Tracy G. Anthony , Elizabeth M. Snyder

Testosterone production by testicular Leydig cells (steroidogenesis) is vital to male fertility and overall male health. Information about how nutrition influences Leydig cell steroidogenesis is lacking. Branched chain amino acids (BCAAs – leucine, isoleucine, and valine) are essential amino acids and important regulators of protein synthesis and energy production. Circulating and tissue BCAA levels are tightly regulated by the enzyme branched chain a-keto acid dehydrogenase kinase (BCKDK), which inhibits their catabolism. This work explored how BCAAs, and especially leucine, modulate male fertility and testosterone production. In a mutant mouse model of Bckdk, breeding analysis showed reduced male fertility and circulating testosterone. Further, morphological evaluation demonstrated testicular and epididymal abnormalities consistent with abnormal testicular androgen signaling. Fertility was partially rescued by feeding a high protein diet while circulating testosterone was not. In wild type testes, Leydig cells were the primary cell type to express BCKDK. Leveraging a primary interstitial cell culture, cell survival and apoptosis analyses demonstrated Leydig cells are highly sensitive to leucine deprivation and this sensitivity is enhanced under steroidogenesis stimulating conditions. Lastly, using the same primary cell culture system, testosterone production was shown to be lost under leucine deprivation. In total, this work demonstrates Leydig cells are uniquely sensitive to BCAA status under steroidogenesis stimulation and that regulated BCAA catabolism may be important for optimal male fertility.

睾丸间质细胞产生睾丸激素（类固醇生成）对男性生育能力和整体男性健康至关重要。关于营养如何影响间质细胞类固醇生成的信息是缺乏的。支链氨基酸（BCAAs -亮氨酸、异亮氨酸和缬氨酸）是必需氨基酸，是蛋白质合成和能量生产的重要调节因子。循环和组织BCAA水平受到支链a-酮酸脱氢酶激酶（BCKDK）的严格调控，BCKDK抑制其分解代谢。这项工作探讨了支链氨基酸，尤其是亮氨酸，如何调节男性生育能力和睾丸激素的产生。在Bckdk突变小鼠模型中，育种分析显示雄性生育能力和循环睾酮水平降低。此外，形态学评估显示睾丸和附睾异常与睾丸雄激素信号异常一致。通过喂食高蛋白饮食，生育能力得到了部分恢复，而循环睾酮则没有。在野生型睾丸中，间质细胞是表达BCKDK的主要细胞类型。利用原代间质细胞培养、细胞存活和凋亡分析表明，间质细胞对亮氨酸剥夺高度敏感，这种敏感性在类固醇生成刺激条件下增强。最后，使用相同的原代细胞培养系统，在亮氨酸剥夺的情况下，睾酮的产生被证明是损失的。总之，这项工作表明，在类固醇生成刺激下，间质细胞对BCAA状态非常敏感，调节BCAA分解代谢可能对最佳男性生育能力很重要。

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引用次数: 0

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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