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Bovine ampullary and isthmic epithelial spheroids: proteomic profile and physiological features for in vitro studies of gamete-oviduct interactions 牛壶腹和峡部上皮球体:配子-输卵管相互作用体外研究的蛋白质组学特征和生理特征
IF 2.5 3区 生物学 Q3 REPRODUCTIVE BIOLOGY Pub Date : 2025-08-15 DOI: 10.1016/j.repbio.2025.101057
Coline Mahé , Ludivine Marco , Ludivine Laffont , Marie-Véronique Demattei , Karine Reynaud , Emmanuelle Com , Régis Lavigne , Charles Pineau , Marie Saint-Dizier
After mating or insemination, spermatozoa reach the first part of the oviduct, known as the isthmus, where a subpopulation binds to the epithelial cilia, forming a reservoir. Then, spermatozoa migrate toward the ampulla, where additional interactions with cilia occur and fertilization takes place. Exploring sperm-oviduct interactions requires physiologically relevant in vitro models. Our goal was to characterize isthmic and ampullary epithelial spheroids in terms of cellular, proteomic and sperm binding properties. Spheroids measuring 100–150 µm in diameter, formed after a 3-day culture of pre-ovulatory oviduct mucosa fragments, were selected and analyzed for (i) epithelial, fibroblast and cilia markers by immunostaining, (ii) proteomic content by dia-PASEF nanoLC-MS/MS, and (iii) ability to interact with bull spermatozoa during a 6-h co-culture, assessed by confocal and scanning electron microscopy. Cells within both isthmic and ampullary spheroids showed positive immunostaining for cytokeratin and no staining for vimentin. Ampullary spheroids consistently exhibited a higher proportion of ciliated cells compared to isthmic spheroids (24.5 % vs 20 %; p < 0.05; variation coefficients among replicates of 15 and 11 %, respectively). A total of 6914 proteins were quantified, of which 1010 (14 %) were differentially abundant between isthmic and ampullary spheroids. Following co-culture, 95–97 % of bound spermatozoa were attached by their head to cilia of both spheroid groups. The density of bound spermatozoa was on average 33–45 % higher on ampullary compared to isthmic spheroids (p < 0.001). This study provides a well-differentiated oviduct epithelium model for in vitro investigations of gamete and embryo interactions with the oviduct.
在交配或授精后,精子到达输卵管的第一部分,即峡部,在那里一个亚群与上皮纤毛结合,形成一个储存库。然后,精子向壶腹移动,在那里与纤毛发生额外的相互作用并受精。探索精子-输卵管相互作用需要生理相关的体外模型。我们的目标是在细胞,蛋白质组学和精子结合特性方面表征峡部和壶腹上皮球体。在排卵前输卵管粘膜片段培养3天后形成直径为100-150 µm的球体,选择并分析(i)通过免疫染色检测上皮、成纤维细胞和纤毛标志物,(ii)通过dia-PASEF nanoLC-MS/MS检测蛋白质组学含量,以及(iii)通过共聚焦和扫描电子显微镜评估在6小时共培养过程中与公牛精子相互作用的能力。峡部和壶腹球体内的细胞角蛋白免疫染色阳性,而波形蛋白未染色。壶腹球体比峡部球体始终显示出更高比例的纤毛细胞(24.5% % vs 20% %;p & lt; 0.05;重复间变异系数分别为15和11 %)。共检测到6914个蛋白,其中1010个(14 %)在壶腹和峡部球体之间差异丰富。共培养后,95 - 97% %的结合精子头部附着在两组的纤毛上。壶腹结合精子密度比峡部球体平均高33-45 % (p <; 0.001)。本研究为体外研究配子和胚胎与输卵管的相互作用提供了一个分化良好的输卵管上皮模型。
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引用次数: 0
Protective role of gallic acid in sperm health and environmentally induced male infertility: A narrative review of human-relevant and translational preclinical studies 没食子酸在精子健康和环境诱导的男性不育中的保护作用:对人类相关和转化性临床前研究的述评
IF 2.5 3区 生物学 Q3 REPRODUCTIVE BIOLOGY Pub Date : 2025-08-13 DOI: 10.1016/j.repbio.2025.101055
Weitian Chen , Junfeng Qiu , Zhiming Hong , Jinjun Yuan , Quan Wang , Wenbin Zhou
Male infertility has become a growing global concern due to the decline in sperm quality, largely influenced by environmental toxins, aging, and lifestyle factors. This comprehensive review investigates the potential protective effects of gallic acid (GA), a natural phenolic compound, against various forms of male infertility. GA’s antioxidant, anti-inflammatory, and anti-apoptotic properties are explored in the context of sperm health and reproductive dysfunctions induced by environmental toxins, oxidative stress, and drug treatments. The paper highlights preclinical studies demonstrating GA’s ability to improve sperm quality, enhance testicular function, and restore hormonal balance. Key findings show that GA can mitigate testicular damage, reduce oxidative stress, and promote spermatogenesis in response to stressors such as chemotherapy, phthalates, and nicotine exposure. Moreover, GA’s potential in sperm cryopreservation and fertility preservation is also examined. This review emphasizes the therapeutic promise of GA as a natural agent in supporting male reproductive health and offers insight into its molecular mechanisms. These data collectively justify immediate clinical translation, specifically, well-controlled phase I/II trials that define GA’s optimal dose, safety, pharmacokinetics, and efficacy on validated reproductive endpoints.
由于精子质量下降,很大程度上受环境毒素、衰老和生活方式因素的影响,男性不育症已成为一个日益受到全球关注的问题。这篇综合综述调查了没食子酸(GA),一种天然酚类化合物,对各种形式的男性不育的潜在保护作用。在环境毒素、氧化应激和药物治疗诱导的精子健康和生殖功能障碍的背景下,探讨了GA的抗氧化、抗炎和抗凋亡特性。这篇论文强调了临床前研究表明GA能够改善精子质量,增强睾丸功能,恢复激素平衡。主要研究结果表明,GA可以减轻睾丸损伤,减少氧化应激,促进精子发生,以应对化疗,邻苯二甲酸盐和尼古丁暴露等应激源。此外,还探讨了GA在精子冷冻保存和生育能力保存方面的潜力。这篇综述强调了GA作为一种支持男性生殖健康的天然药物的治疗前景,并提供了其分子机制的见解。这些数据共同证明了立即的临床转化,特别是控制良好的I/II期试验,这些试验确定了GA的最佳剂量、安全性、药代动力学和在经过验证的生殖终点的有效性。
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引用次数: 0
Surgical management of ovarian torsion in children: Detorsion, cyst/mass excision, and ovarian fixation 儿童卵巢扭转的手术治疗:扭转、囊肿/肿块切除和卵巢固定
IF 2.5 3区 生物学 Q3 REPRODUCTIVE BIOLOGY Pub Date : 2025-08-05 DOI: 10.1016/j.repbio.2025.101054
Serpil Sancar , Meryem Anayurt , Sabriye Dayı
This study evaluated surgical interventions based on the presence or absence of ovarian cysts or masses in pediatric and adolescent patients with ovarian torsion (OT) and analyzed their impact on retorsion development. A retrospective review was conducted on 25 ovaries from 23 patients under 18 years of age who underwent surgery for OT between July 2019 and January 2025. Patients were divided into two groups: Group 1 (n = 14), with ovarian or paraovarian cysts or masses that were excised; and Group 2 (n = 11), without detectable lesions. Detorsion was performed in all cases, and adnexal fixation was selectively applied based on intraoperative findings. All Group 1 patients underwent cyst or mass excision, and no retorsion was observed. All lesions were histologically benign. In Group 2, retorsion occurred in patients with high-risk features such as solitary ovary, elongated uteroovarian ligament, or a history of contralateral torsion. Uteroovarian ligament plication (UOP) was performed in four ovaries from three Group 2 patients. The difference in fixation rates between the groups was statistically significant (p = 0.026). No postoperative complications were noted. Excision of associated cysts or masses may reduce recurrence in OT, while adnexal fixation appears to be a safe, feasible option for lesion-free patients with anatomical risk factors.
本研究评估了儿童和青少年卵巢扭转(OT)患者是否存在卵巢囊肿或肿块的手术干预,并分析了它们对卵巢扭转发展的影响。对2019年7月至2025年1月期间接受OT手术的23名18岁以下患者的25个卵巢进行了回顾性研究。患者分为两组:1组(n = 14),切除卵巢或卵巢旁囊肿或肿块;2组(n = 11),无可检出病变。所有病例均行扭转术,并根据术中发现选择性应用附件固定。所有1组患者均行囊肿或肿块切除,未见复发。所有病变组织学上均为良性。在第2组中,扭转发生在具有高危特征的患者,如卵巢孤立、子宫卵巢韧带拉长或有对侧扭转史。对3例2组患者的4个卵巢行子宫腔韧带夹闭术(UOP)。两组间固定率差异有统计学意义(p = 0.026)。无术后并发症。切除相关的囊肿或肿块可以减少OT的复发,而附件固定对于无病变但有解剖学危险因素的患者来说是一种安全可行的选择。
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引用次数: 0
The impact of dexamethasone on cellular stress responses caused by mild serum deprivation in androgen-insensitive prostate cancer cells 地塞米松对雄激素不敏感前列腺癌细胞轻度血清剥夺引起的细胞应激反应的影响
IF 2.5 3区 生物学 Q3 REPRODUCTIVE BIOLOGY Pub Date : 2025-08-05 DOI: 10.1016/j.repbio.2025.101053
Weronika Broszkiewicz , Jakub Beda , Kamila Domińska
Dexamethasone (DEX), a glucocorticoid receptor agonist, is widely used for prostate cancer therapies, although its exact impact on androgen-independent prostate cancer cells remains unclear. As solid cancers are typically characterized by nutrient-deprived conditions in the tumor microenvironment (TME), the present study examines the effect of DEX on stress responses in DU-145 and PC3 cells caused by mild serum deficiency. It was found that DEX limited the ability of prostate cancer cells to divide and deepened the G0 / G1 cell cycle arrest induced by serum deprivation; it also reduced adhesion by DU-145 and PC3 cells to extracellular matrix proteins, but did not increase migration. However, it improved the survival of androgen-insensitive prostate cancer cells under conditions of mild serum deprivation by preventing apoptosis, reprogramming the glucose and lipid metabolism and restoring the inflammatory balance. We postulate that dexamethasone has a cytostatic rather than cytotoxic effect on androgen-independent prostate cancer cells and that it directs prostate cancer cells to a resting state. Treatment also carries a risk of minimal residual disease (MRD).
地塞米松(Dexamethasone, DEX)是一种糖皮质激素受体激动剂,广泛用于前列腺癌治疗,尽管其对雄激素非依赖性前列腺癌细胞的确切影响尚不清楚。由于实体癌的典型特征是肿瘤微环境(TME)中的营养剥夺状况,本研究考察了DEX对轻度血清缺乏引起的DU-145和PC3细胞应激反应的影响。结果发现,DEX抑制了前列腺癌细胞的分裂能力,加深了血清剥夺诱导的G0 / G1细胞周期阻滞;它还降低了DU-145和PC3细胞对细胞外基质蛋白的粘附,但没有增加迁移。然而,它通过阻止细胞凋亡、重编程糖脂代谢和恢复炎症平衡,提高了雄激素不敏感的前列腺癌细胞在轻度血清剥夺条件下的存活率。我们假设地塞米松对雄激素非依赖性前列腺癌细胞具有细胞抑制作用而不是细胞毒性作用,并指导前列腺癌细胞进入静息状态。治疗也有微小残留病(MRD)的风险。
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引用次数: 0
Comparative study of sperm protamine gene expression and chromatin integrity in Nellore and Angus bulls 内洛尔公牛和安格斯公牛精蛋白基因表达和染色质完整性的比较研究
IF 2.5 3区 生物学 Q3 REPRODUCTIVE BIOLOGY Pub Date : 2025-07-25 DOI: 10.1016/j.repbio.2025.101051
Carlos Alonso Paco Nagaki , Thais Rose dos Santos Hamilton , Camilla Mota Mendes , Mayra Elena Ortiz D’Ávila Assumpção
Methodologies used to evaluate bull fertility often overlook sperm chromatin, a nuclear structure critical for reproductive success due to its DNA composition, which is tightly bound to nucleoproteins called protamines. In mammals, the ratio between Protamine 1 (PRM1) and Protamine 2 (PRM2) plays a pivotal role in male fertility, with imbalances linked to infertility in species such as humans and mice. While bull sperm chromatin was previously believed to contain only PRM1, recent findings have confirmed the presence of PRM2, prompting questions about the impact of the PRM1:PRM2 ratio on bull fertility. The present study hypothesizes that bull infertility may be associated with impaired protamination, resulting in imbalances between PRM1 and PRM2 gene expression. The objective was to compare the chromatin structure through protamine deficiency (CMA3), DNA susceptibility to fragmentation, and PRM1 and PRM2 gene expression among bulls of differing in vivo fertility levels (high fertility and low fertility) and breeds (Nellore and Angus). Sperm from 14 Nellore and 20 Angus bulls with high and low in vivo fertility were analyzed for protamine deficiency, susceptibility to DNA fragmentation, and PRM1 and PRM2 gene expression. Additionally, PRM1:PRM2 ratios were calculated for each experimental group. Results revealed solely a breed effect. Nellore sperm exhibited lower susceptibility to DNA fragmentation and higher PRM1 and PRM2 total transcripts compared to Angus. Conversely, Nellore sperm also demonstrated greater susceptibility to protamine deficiency. Protamine composition may not explain fertility differences, it could play a significant role in adaptive mechanisms across bull breeds.
用于评估公牛生育能力的方法经常忽略精子染色质,这是一种核结构,由于其DNA组成而对生殖成功至关重要,它与称为精蛋白的核蛋白紧密结合。在哺乳动物中,鱼精蛋白1 (PRM1)和鱼精蛋白2 (PRM2)之间的比例在雄性生育能力中起着关键作用,在人类和小鼠等物种中,这种失衡与不育有关。虽然以前认为公牛精子染色质只含有PRM1,但最近的研究结果证实了PRM2的存在,这引发了关于PRM1:PRM2比例对公牛生育能力影响的问题。本研究假设公牛不育可能与蛋白化受损有关,导致PRM1和PRM2基因表达不平衡。目的是比较不同体内生育水平(高生育能力和低生育能力)和品种(Nellore和Angus)公牛的染色质结构(CMA3)、DNA断裂易感性和PRM1和PRM2基因表达。分析了14头内洛尔公牛和20头安格斯公牛体内高育性和低育性精子的鱼精蛋白缺乏、DNA片段化易感性和PRM1和PRM2基因表达情况。并计算各实验组的PRM1:PRM2比值。结果显示仅存在品种效应。与安格斯相比,Nellore精子对DNA断裂的易感性较低,PRM1和PRM2总转录本较高。相反,Nellore精子也表现出对鱼精蛋白缺乏的更大敏感性。鱼精蛋白的组成可能不能解释繁殖力的差异,但它可能在不同公牛品种的适应机制中发挥重要作用。
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引用次数: 0
Cryptorchidism-induced disruption of TRPM8 expression and calcium signaling in canine testes: A potential mechanism for tumourigenesis 隐睾诱导的TRPM8表达和钙信号在犬睾丸中的破坏:肿瘤发生的潜在机制
IF 2.5 3区 生物学 Q3 REPRODUCTIVE BIOLOGY Pub Date : 2025-07-25 DOI: 10.1016/j.repbio.2025.101052
Anna Gałuszka , Wojciech Łopuszyński , Patrycja Kurowska , Katarzyna Kotarska , Agnieszka Rak , Piotr Pawlicki
Cryptorchidism is a condition where one or both testes fail to descend, increasing the risk of tumour development. This study investigated histological and molecular changes in canine cryptorchid testes, focusing on the TRPM8 calcium channel and its potential role in tumour-related signaling pathways. Histological and molecular changes in cryptorchid canine testes, focusing on the role of TRPM8, as well as the expression of PRKCA, MAPK1, and MAPK3 at both mRNA and protein levels, and intracellular calcium ion (Ca2 +) accumulation. Testicular tissues were collected from 14 middle-aged canine, including six with unilateral cryptorchidism. Histological analysis revealed a significant depletion of germ cells and extensive fibrosis in cryptorchid testes. Immunostaining analyses showed reduced expression and altered localization of TRPM8 in cryptorchid testes. Significant differences in TRPM8 transcript level were observed between control scrotal testes and cryptorchid testes, as well as between contralateral and cryptorchid testes (P < 0.01). Western blot analysis revealed a substantial decrease in TRPM8 protein levels (P < 0.001), accompanied by an increase in PKCα and ERK1/2 proteins (P < 0.001) in cryptorchid testes compared to control scrotal testes. Mean fluorescence intensity analysis showed a significantly lower accumulation of intracellular Ca2 + in cryptorchid testes (P < 0.01). The reduced TRPM8 expression and disrupted calcium signaling could activate pro-proliferative PKC/MAPK pathways, promoting tumourigenesis. These results underscore TRPM8’s role in calcium homeostasis and suggest its dysregulation in canine cryptorchidism could predispose to developing testicular cancer. Targeting TRPM8 and related pathways could offer new therapeutic strategies in veterinary and human oncology.
隐睾症是一个或两个睾丸不能下降的一种情况,增加了肿瘤发展的风险。本研究研究了犬隐睾的组织学和分子变化,重点研究了TRPM8钙通道及其在肿瘤相关信号通路中的潜在作用。隐睾犬睾丸的组织学和分子变化,重点关注TRPM8的作用,以及PRKCA、MAPK1和MAPK3在mRNA和蛋白水平上的表达,以及细胞内钙离子(Ca2 +)的积累。收集了14只中年犬的睾丸组织,其中6只为单侧隐睾。组织学分析显示隐睾有明显的生殖细胞损耗和广泛的纤维化。免疫染色分析显示,TRPM8在隐睾中的表达降低,定位改变。对照阴囊与隐睾、对侧睾丸与隐睾之间TRPM8转录本水平差异有统计学意义(P <; 0.01)。Western blot分析显示,与对照阴囊睾丸相比,隐睾中TRPM8蛋白水平显著降低(P <; 0.001),同时PKCα和ERK1/2蛋白水平升高(P <; 0.001)。平均荧光强度分析显示,隐睾细胞内Ca2 + 的积累显著降低(P <; 0.01)。TRPM8表达的降低和钙信号的中断可以激活促增殖的PKC/MAPK通路,促进肿瘤的发生。这些结果强调了TRPM8在钙稳态中的作用,并提示其在犬隐睾症中的失调可能导致睾丸癌的发生。靶向TRPM8及其相关通路可能为兽医和人类肿瘤的治疗提供新的策略。
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引用次数: 0
Use of an exogenous DNA-free system to generate MSTN-KO calves by CRISPR/Cas9 and SCNT 使用外源无dna系统通过CRISPR/Cas9和SCNT生成MSTN-KO小牛
IF 2.5 3区 生物学 Q3 REPRODUCTIVE BIOLOGY Pub Date : 2025-07-15 DOI: 10.1016/j.repbio.2025.101050
Mariana Suvá , Juan Ignacio Bastón , Elisabet Astrid Wiedenmann , María Belén Pose Ortiz de Rozas , Roberto Jordán , Alberto Ghetti , Diego Luis Viale , Lucia Natalia Moro , Gabriel Damián Vichera
This study aimed to obtain myostatin (MSTN)-knockout calves, while avoiding the risk of exogenous DNA integration during gene editing. To achieve this, we combined CRISPR/Cas9 ribonucleoprotein gene editing with somatic cell nuclear transfer (SCNT) technology.
In the first experiment (E1), we compared the gene editing efficiency of four gRNAs targeting different coding regions of the MSTN gene using plasmid-based CRISPR/Cas9 in bovine fetal fibroblasts (BFF-E1 cells). The highest bioinformatically-predicted editing rate (BPE) was obtained with gRNA2 (96 %), which was subsequently used for further experiments. Next, embryos were produced by SCNT using BFF-E1-edited cells as nuclear donors. Sanger sequencing of the embryos showed biallelic MSTN editing. In the second experiment (E2), plasmid-based editing was replaced with CAS9 protein and trac:crRNA oligoribonucleotides. Editing efficiency was assessed on one edited bovine fetal fibroblast line (BFF-E2-maleed) and two edited bovine mesenchymal stem lines (MSC-E2-maleed and MSC-E2-femed) derived from price-winning animals. BPEs were 58.8 %, 31 % and 59 % in fibroblast and MSC cells, and 64 %, 73.3 %, and 66.6 % in SCNT embryos derived from BFF-E2-maleed, MSC-E2-maleed and MSC-E2-femed, respectively.
Transfer of 35 MSC-E2-femed embryos to recipient cows, resulted in the birth of one MSTN-edited calf with a heterozygous genotype. A second-generation clone was subsequently produced, using a fibroblast sample as nuclear donor.
In conclusion, we established an efficient protocol for generating high rates of edited blastocysts with a desirable genetic background, resulting in the birth of two MSTN-knockout calves. This study provides a foundation for gene editing to improve productive or biomedical traits.
这项研究旨在获得肌肉生长抑制素(MSTN)敲除小牛,同时避免基因编辑过程中外源DNA整合的风险。为此,我们将CRISPR/Cas9核糖核蛋白基因编辑与体细胞核移植(SCNT)技术相结合。在第一个实验(E1)中,我们使用基于质粒的CRISPR/Cas9在牛胎儿成纤维细胞(BFF-E1细胞)中比较了四种靶向MSTN基因不同编码区的gRNAs的基因编辑效率。使用gRNA2获得了最高的生物信息预测编辑率(BPE)(96 %),随后将其用于进一步的实验。接下来,使用bff - e1编辑的细胞作为核供体,通过SCNT产生胚胎。胚胎的Sanger测序显示双等位基因MSTN被编辑。在第二个实验(E2)中,用CAS9蛋白和trac:crRNA寡核苷酸取代了基于质粒的编辑。对一个编辑过的牛胚胎成纤维细胞系(BFF-E2-maleed)和两个编辑过的牛间充质干细胞细胞系(MSC-E2-maleed和MSC-E2-femed)的编辑效率进行了评估。成纤维细胞和MSC细胞的bpe分别为58.8% %、31 %和59 %,BFF-E2-maleed、MSC- e2 -maleed和MSC- e2 -femed的SCNT胚胎的bpe分别为64 %、73.3 %和66.6% %。将35个msc - e2胚胎移植到受体奶牛身上,产生了一头带有杂合基因型的mstn编辑小牛。随后用成纤维细胞样本作为核供体,产生了第二代克隆体。总之,我们建立了一种高效的方案,用于产生具有理想遗传背景的高比率编辑囊胚,从而产生了两只mstn敲除小牛。该研究为基因编辑改善生产或生物医学性状提供了基础。
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引用次数: 0
Evaluation of the relative gene expression of FGF2, HAS2, BCL2, VEGFA, and PGR in repeat-breeder cows undergoing cyclicity or acyclicity FGF2、HAS2、BCL2、VEGFA和PGR基因在循环和非循环状态下的相对表达评价
IF 2.5 3区 生物学 Q3 REPRODUCTIVE BIOLOGY Pub Date : 2025-07-03 DOI: 10.1016/j.repbio.2025.101049
Punnawut Yama , Napatsorn Montha , Jakree Jitjumnong , Hien Van Doan , Nguyen Vu Linh , Warittha U-krit , Maslin Osathanunkul , Raktham Mektrirat , Julakorn Panatuk , Payungsuk Intawicha , Chien-Kai Wang , Tossapol Moonmanee
Repeat breeder syndrome (RBS) is one of the main reproductive failures in mono-ovulatory dairy cattle. The differential relative expression of several important genes in the ovary and uterus were evaluated in repeat-breeder dairy cattle. Cows classified as RBS, defined as those that had failed to conceive after at least three consecutive inseminations, with no clinical abnormalities. The selected cows were divided into two groups: repeat-breeder dairy cows undergoing cyclicity (control group) (n = 8) or acyclicity (n = 6). Granulosa cells (GCs) and endometrium were collected from both groups to evaluate the relative expression levels of target genes (fibroblast growth factor 2 [FGF2], hyaluronan synthase 2 [HAS2], B-cell lymphoma 2 [BCL2], vascular endothelial growth factor A [VEGFA], and progesterone receptor [PGR]). The relative expression levels of FGF2 mRNA in GCs (0.34-fold and –65.84 %) and PGR mRNA in endometrium (0.09-fold and –90.53 %) were lower (P < 0.05) in acyclic cows relative to cyclic cows. The relative expression levels of HAS2 and BCL2 mRNA in GCs tended to be lower by 0.40-fold (–59.85 %, P = 0.084) and 0.54-fold (–45.84 %, P = 0.065) in acyclic cows relative to cyclic cows. However, none of the relative expression levels of VEGFA in the ovary and uterus differed between groups (P > 0.10). These results provide a comparison of differential gene expression in repeat-breeder dairy cows undergoing cyclicity and acyclicity, suggesting a role in ovarian follicular growth and uterine function.
重复繁殖综合征(RBS)是单排卵奶牛繁殖失败的主要原因之一。研究了重复种牛卵巢和子宫中几个重要基因的差异相对表达。被归类为RBS的奶牛,定义为在至少连续三次人工授精后未能怀孕,没有临床异常的奶牛。将选取的奶牛分为两组:循环奶牛组(n = 8)和不循环奶牛组(n = 6)。采集两组患者的颗粒细胞(GCs)和子宫内膜,评估靶基因(成纤维细胞生长因子2 [FGF2]、透明质酸合成酶2 [HAS2]、b细胞淋巴瘤2 [BCL2]、血管内皮生长因子A [VEGFA]、孕激素受体[PGR])的相对表达水平。非循环奶牛GCs中FGF2 mRNA的相对表达量(0.34倍,-65.84 %)和子宫内膜中PGR mRNA的相对表达量(0.09倍,-90.53 %)低于循环奶牛(P <; 0.05)。HAS2和BCL2 mRNA在GCs中的相对表达量相对于循环奶牛有降低0.40倍(-59.85 %,P = 0.084)和0.54倍(-45.84 %,P = 0.065)的趋势。然而,各组间卵巢和子宫中VEGFA的相对表达量均无差异(P >; 0.10)。这些结果提供了在周期性和非周期性重复繁殖奶牛中差异基因表达的比较,提示其在卵巢卵泡生长和子宫功能中起作用。
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引用次数: 0
The impact of bisphenol A and its analogs on female reproductive health 双酚A及其类似物对女性生殖健康的影响
IF 2.5 3区 生物学 Q3 REPRODUCTIVE BIOLOGY Pub Date : 2025-07-03 DOI: 10.1016/j.repbio.2025.101028
Ewelina Trela-Kobędza, Anna Ajduk
The number of pollutants stemming from anthropogenic chemicals is increasing every year. Some of them act similarly to hormones and are referred to as endocrine-disrupting chemicals or endocrine disruptors. In this group, bisphenol A (BPA) is well characterized as a xenoestrogen and is known to affect human health. BPA is crucial to the production of plastic, a material that has revolutionized and facilitated daily life. Nevertheless, the use of BPA is currently being limited, and consequently, new BPA analogs are under development. However, both BPA and its analogs can be released into the environment during their manufacturing process and daily usage. In conjunction with the escalating demand for plastics and the prolonged persistence of plastic waste, it poses a substantial threat to human health. In this article, we concentrate on the influence of BPA and its most common analogs (bisphenol S, bisphenol F, bisphenol AF, bisphenol Z, bisphenol P, bisphenol AP, bisphenol B) on female reproductive health. We reviewed the existing epidemiological data (or in the absence of it, data obtained from animal and in vitro models) on their impact on hormone levels, oocyte yield, oocyte and embryo quality, implantation and pregnancy success, polycystic ovary syndrome, and endometriosis. We also discuss metabolism of bisphenols, their mechanism of action and impact on cellular physiology, as well as current regulations on their use. Our comprehensive review reveals that, despite existing discrepancies, a substantial body of evidence suggests that bisphenols influence female reproductive health. This underscores the urgent need for future regulatory measures to limit and regulate the use of bisphenols.
由人为化学物质产生的污染物的数量每年都在增加。它们中的一些作用类似于激素,被称为内分泌干扰化学物质或内分泌干扰物。在这一组中,双酚A (BPA)被认为是一种雌激素,已知会影响人体健康。双酚a对塑料的生产至关重要,塑料是一种彻底改变和促进日常生活的材料。然而,双酚a的使用目前是有限的,因此,新的双酚a类似物正在开发中。然而,双酚a及其类似物在制造过程和日常使用中都会释放到环境中。再加上对塑料的需求不断增加和塑料废物长期存在,它对人类健康构成了重大威胁。在本文中,我们主要关注双酚a及其最常见的类似物(双酚S、双酚F、双酚AF、双酚Z、双酚P、双酚AP、双酚B)对女性生殖健康的影响。我们回顾了现有的流行病学数据(或在没有流行病学数据的情况下,从动物和体外模型获得的数据),研究它们对激素水平、卵母细胞产量、卵母细胞和胚胎质量、着床和妊娠成功率、多囊卵巢综合征和子宫内膜异位症的影响。我们还讨论了双酚类物质的代谢、作用机制和对细胞生理的影响,以及目前对其使用的规定。我们的综合审查显示,尽管存在差异,但大量证据表明双酚类物质影响女性生殖健康。这强调了今后迫切需要采取管制措施来限制和管制双酚类物质的使用。
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引用次数: 0
The postnatal offspring of finasteride-treated male rats show altered ERα and PCNA expression in the liver 非那雄胺处理的雄性大鼠出生后的后代肝脏中ERα和PCNA表达发生改变
IF 2.5 3区 生物学 Q3 REPRODUCTIVE BIOLOGY Pub Date : 2025-07-02 DOI: 10.1016/j.repbio.2025.101044
Agnieszka Kolasa , Paulina Kur , Sylwia Rzeszotek , Marta Grabowska , Małgorzata Blatkiewicz , Marika Freus , Aleksandra Wilk
A growing body of data indicates that the physiology of the liver is sex-hormone dependent, with some types of liver failure occurring more frequently in males, and some in females. In males, in physiological conditions, estrogens acts via estrogen receptors (ERs). Estrogen may promote liver tumorigenesis, due to the increased hepatocyte mitogenic activity or may cause regression of hypertrophic liver nodules or, as in the case of hepatic adenocarcinoma, may reduce the estrogen-binding ability of hepatocytes. In our previous studies, we demonstrated biochemical changes in blood parameters as well as physiological and morphological changes in the liver of male rats from the paternal generation receiving finasteride. Therefore, the goal of the study was to assess whether the administration of finasteride has an intergenerational effect on ERα and PCNA (to detect mitotic activity) expression in the hepatocytes of male rat offspring. The study was conducted on the liver from immature (7, 14, 21, 28 days age) and mature (90 days age) Wistar male rats (F1:Fin) born by females fertilized by finasteride-treated rats. The control group was the offspring (F1:Control) of untreated Wistar parents. After the IHC reaction, the slides were undergoing Quantitative Computer Image Analysis. We demonstrated an altered pattern of immunoexpression level of the studied markers in the F1:Control vs F1:Fin groups. We noticed a positive (F1:Control 7PND, postnatal days) and negative (F1:Control 90PND) correlation between ERα and PCNA immunoexpression. Additionally, the expression of ERα and PCNA was examined at the mRNA level. This paper is documenting that finasteride use by paternal generation males (in reproductive age) may lead to an intergenerational effect detrimental to the liver function of their male offspring.
越来越多的数据表明,肝脏的生理机能依赖于性激素,有些类型的肝功能衰竭更常发生在男性身上,有些更常发生在女性身上。在男性中,在生理条件下,雌激素通过雌激素受体(er)起作用。由于肝细胞有丝分裂活性的增加,雌激素可能促进肝脏肿瘤的发生,也可能导致肥厚性肝结节的消退,或者像在肝腺癌的情况下,可能降低肝细胞的雌激素结合能力。在我们之前的研究中,我们证明了父亲代的雄性大鼠接受非那雄胺后血液参数的生化变化以及肝脏的生理和形态变化。因此,本研究的目的是评估非那雄胺给药是否对雄性大鼠后代肝细胞中ERα和PCNA(检测有丝分裂活性)表达有代际影响。本研究采用未成熟(7、14、21、28日龄)和成熟(90日龄)Wistar雄性大鼠(F1:Fin)与非那雄胺处理大鼠受精后所生的肝脏。对照组为未处理Wistar亲本的后代(F1: control)。免疫组化反应后,对载玻片进行定量计算机图像分析。我们证明了F1:Control组与F1:Fin组中所研究标记物的免疫表达水平的改变模式。我们注意到ERα和PCNA免疫表达呈正相关(F1:对照7PND,出生后)和负相关(F1:对照90PND)。在mRNA水平上检测ERα和PCNA的表达。本文记录了父亲代男性(育龄期)使用非那雄胺可能导致对其男性后代肝功能有害的代际效应。
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Reproductive biology
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