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Trps1 targets Scarb1 to regulate cholesterol acquisition in mouse Leydig cells Trps1靶向Scarb1调节小鼠间质细胞中的胆固醇获取
IF 2.5 3区 生物学 Q3 REPRODUCTIVE BIOLOGY Pub Date : 2025-09-01 Epub Date: 2025-06-18 DOI: 10.1016/j.repbio.2025.101046
Xiuli Lian , Zihang Lin , Weitao Hu , Zhangting Chen , Shanshan Luo , Shumin Liao , Yue Liu , Shie Wang , Jiandong Sun
Approximately 7 % of men are suffering from infertility, accounting for 40 %-50 % of all cases of all infertility, and low testosterone levels are closely associated with male infertility. Our previous study indicated that transcriptional repressor GATA binding 1 (Trps1) could inhibit testosterone synthesis in Leydig cells. In the present study, to elucidate the molecular mechanism by which Trps1 regulates testosterone synthesis in Leydig cells, differentially expressed genes (DEGs) following Trps1 knockdown was conducted by RNA-sequencing. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Genes ontology (GO) analysis were utilized to investigate the pathways associated with Trps1. Gene-silencing technology, Real-Time PCR, and Western blot were performed to validate DEGs. In addition, testosterone and cellular cholesterol content were further observed. We found that GO analysis of DEGs associated with “cholesterol metabolism”. Real-Time PCR and Western blot showed that the expression of steroidogenic factor-1 (Sf-1) and scavenger receptor class B, member 1 (Scarb1) were up-regulated after Trps1 silencing. Knockdown of Sf-1 and Scarb1 could revert the elevated testosterone and cellular cholesterol levels caused by Trps1 deficiency. Moreover, ChIP-seq and CUT&Tag-qPCR demonstrated that the promoter of Scarb1 has a binding site for SF-1. The present study revealed that TRPS1 exerts regulatory control over the expression of Scarb1 by modulating Sf-1 transcriptional activity, thereby enhancing cholesterol level and promoting the synthesis of testosterone in Leydig cells.
大约7 %的男性患有不育症,占所有不育症病例的40 %-50 %,睾丸激素水平低与男性不育症密切相关。我们之前的研究表明,转录抑制因子GATA结合1 (Trps1)可以抑制间质细胞的睾酮合成。为了阐明Trps1在间质细胞中调控睾酮合成的分子机制,本研究通过rna测序对Trps1敲低后的差异表达基因(DEGs)进行了研究。利用京都基因与基因组百科全书(KEGG)富集分析和基因本体(GO)分析来研究与Trps1相关的途径。采用基因沉默技术、Real-Time PCR和Western blot对deg进行验证。此外,进一步观察睾酮和细胞胆固醇含量。我们发现DEGs的氧化石墨烯分析与“胆固醇代谢”相关。Real-Time PCR和Western blot结果显示,Trps1沉默后,甾体生成因子-1 (Sf-1)和清道夫受体B类成员1 (Scarb1)的表达上调。敲低Sf-1和Scarb1可以恢复Trps1缺乏引起的睾酮和细胞胆固醇水平升高。此外,ChIP-seq和CUT&;Tag-qPCR证实Scarb1的启动子具有SF-1的结合位点。本研究发现TRPS1通过调节Sf-1转录活性调控Scarb1的表达,从而提高间质细胞胆固醇水平,促进睾酮合成。
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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 : 2025-09-01 Epub 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
Summarizing the human genes and their variants causative of non-obstructive azoospermia uncovered using whole genome/exome sequencing 总结利用全基因组/外显子组测序发现的导致非阻塞性无精子症的人类基因及其变异
IF 2.5 3区 生物学 Q3 REPRODUCTIVE BIOLOGY Pub Date : 2025-09-01 Epub Date: 2025-06-27 DOI: 10.1016/j.repbio.2025.101048
Rim Ibrahim, Agnieszka Malcher , Maciej Kurpisz
Azoospermia represents 15 % of male infertility cases and is characterized by the total absence of sperm cells in the ejaculate. Recent studies on non-obstructive azoospermia (NOA) underline the significance of genetic diagnosis such as whole-exome sequencing (WES) and whole-genome sequencing (WGS) to identify the genetic causes of the disease. In this review, we aim to pinpoint genes and their variants uncovered to date related to NOA using next-generation sequencing. We also provide a unique functional classification of NOA-related genes. Furthermore, we highlight the importance of consanguineous families for uncovering genes and their variants, a point that is largely missing in other reviews. We included all relevant article types, regardless of their publication period, and excluded the articles related to the AZF region. Gene expression data in human and mouse testes were sourced from the NCBI Gene database. The localization/expression of genes were explored using Human Protein Atlas (single-cell type). 230 genes related to azoospermia were identified, divided and categorized based on their function in spermatogenesis and their expression level in the testis. We also highlighted the gene and its variants uncovered in consanguineous families. This review represents a step closer to the creation of a NOA gene panel essential for the routine diagnosis of infertility and perhaps a future strategy for treatment.
无精子症占男性不育病例的15% %,其特征是射精中完全没有精子细胞。最近关于非阻塞性无精子症(NOA)的研究强调了基因诊断的重要性,如全外显子组测序(WES)和全基因组测序(WGS)来确定疾病的遗传原因。在这篇综述中,我们的目标是利用新一代测序技术查明迄今为止发现的与NOA相关的基因及其变异。我们还提供了一个独特的功能分类noaa相关基因。此外,我们强调近亲家庭对于发现基因及其变异的重要性,这一点在其他综述中基本上是缺失的。我们纳入了所有相关的文章类型,不论其发表时间,并排除了与AZF地区相关的文章。人类和小鼠睾丸的基因表达数据来源于NCBI基因数据库。利用人类蛋白图谱(Human Protein Atlas,单细胞型)研究基因的定位和表达。根据230个无精子症相关基因在精子发生中的功能及其在睾丸中的表达水平,对其进行了鉴定、划分和分类。我们还强调了在近亲家庭中发现的基因及其变异。这一综述表明,我们离建立对不孕症的常规诊断至关重要的NOA基因小组又近了一步,或许还能成为未来的治疗策略。
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引用次数: 0
Chronic stress disturbs neuroendocrine control of reproduction and fertility in male rats 慢性应激干扰雄性大鼠生殖和生育的神经内分泌控制
IF 2.5 3区 生物学 Q3 REPRODUCTIVE BIOLOGY Pub Date : 2025-09-01 Epub Date: 2025-05-24 DOI: 10.1016/j.repbio.2025.101027
Habit Medina , Alejandra Flores , Lizbeth Juárez-Rojas , Fahiel Casillas , Mohammad Mehdi Ommati , Reza Heidari , Sara Vázquez , Denise Clavijo-Cornejo , Sheila Peña-Corona , Socorro Retana-Márquez
Currently, stress is considered one of the risk factors for infertility in male humans, altering sperm function. Sperm production and maturation depends on the hypothalamic-pituitary-testis axis control. Therefore, the objective of the current study was to evaluate the effects of chronic stress on the neuroendocrine control of male reproduction, the oxidative status in the epididymis, and male fertility. Adult male rats were assigned to control or chronic stress groups. Chronically stressed males were exposed to cold-water immersion (CWI) for 50 consecutive days. After euthanasia, the hypothalamus was dissected for Kisspeptin (Kiss1) and Gonadotropin releasing hormone (GnRH) evaluation; serum luteinizing hormone (LH), testosterone (T), and corticosterone concentrations were determined. In the epididymis, reactive oxygen species (ROS), lipid peroxides, and content of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx4) were assessed. Sperm motility, viability, concentration, morphology and acrosomal reaction were assessed. Epididymal sperm were used for in-vitro fertilization with oocytes from intact female rats. Stressed males showed lower hypothalamic Kiss1 and GnRH content, lower LH and T concentration, together with higher serum corticosterone concentration. ROS production, and lipid peroxides increased in all epididymal regions, while SOD, CAT, and GPx4 content decreased after chronic stress; sperm quality was also lower. The percentage of fertilized oocytes decreased, and embryonic development was low, compared to controls. Together, these results show that chronic stress disrupts neuroendocrine control of male reproduction and generates oxidative stress in the epididymis. These effects disturb sperm quality, leading to low fertilizing potential and poor embryonic development.
目前,压力被认为是男性不育的危险因素之一,它会改变精子的功能。精子的产生和成熟取决于下丘脑-垂体-睾丸轴的控制。因此,本研究的目的是评估慢性应激对男性生殖神经内分泌控制、附睾氧化状态和男性生育能力的影响。将成年雄性大鼠分为对照组和慢性应激组。长期应激雄鼠连续50天浸泡在冷水中。安乐死后解剖下丘脑进行Kisspeptin (Kiss1)和促性腺激素释放激素(GnRH)评估;测定血清黄体生成素(LH)、睾酮(T)和皮质酮浓度。测定附睾中活性氧(ROS)、脂质过氧化物以及超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GPx4)的含量。评估精子活力、活力、浓度、形态和顶体反应。用完整雌鼠附睾精子与卵母细胞进行体外受精。应激雄性下丘脑Kiss1和GnRH含量降低,LH和T浓度降低,血清皮质酮浓度升高。慢性应激后附睾各区域ROS和脂质过氧化物含量均升高,SOD、CAT和GPx4含量降低;精子质量也较低。与对照组相比,受精卵的百分比下降,胚胎发育较低。总之,这些结果表明,慢性应激破坏了男性生殖的神经内分泌控制,并在附睾中产生氧化应激。这些影响会影响精子质量,导致受精率低和胚胎发育不良。
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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 : 2025-09-01 Epub 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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引用次数: 0
Physical activity pattern and Pre-eclampsia risk biomarkers: an observational study 体育活动模式和子痫前期风险生物标志物:一项观察性研究
IF 2.5 3区 生物学 Q3 REPRODUCTIVE BIOLOGY Pub Date : 2025-09-01 Epub Date: 2025-06-18 DOI: 10.1016/j.repbio.2025.101047
Ana M. Cagiao , Pablo Díaz-Brage , Manuel-Avelino Giráldez , Marta Torres-Tarrío , Melissa L. Erickson , Elvis A. Carnero
Screening tests for preterm pre-eclampsia (PE) include maternal risk factors, mean arterial blood pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF). Exercise interventions have been shown to improve vascular function in pregnant women, which could mediate improvements in angiogenic balance. However, few studies have analyzed how sedentarism and/or physical activity levels are associated with biomarkers of PE. The aim of this study was to analyze the associations between objectively measured physical activity and sedentarism levels with PE risk biomarkers. We hypothesized that higher PA levels would be associated with lower MAP and UtA-PI, and higher PlGF. This was an ancillary study with a convenience sampling from a larger cohort (PREVAL study). Physical activity and sedentarism levels were objectively measured by actigraphy (GT9X Actigraph) in 21 women during the first trimester of pregnancy. We measured PE biomarkers: UtA-PI by ultrasound, PlGF in serum and MAP with a digital sphygmomanometer. The sample was stratified in 2 groups for both physical activity and sedentarism level. Comparisons between groups for PE biomarkers were performed using T-test or Mann Whitney U-test. The level of significance was set at 0.05. PlGF was 57.6 % higher in the active group than in the low-active group (P = 0.018). UtA-PI and MAP were lower in the active group and low-sedentary group although differences were not significant. Moderate-vigorous physical activity (MVPA) was associated with PlGF levels. Therefore, our study suggests a plausible connection between MVPA and biomarkers of PE.
早产子痫前期(PE)筛查试验包括产妇危险因素、平均动脉血压(MAP)、子宫动脉搏动指数(UtA-PI)和血清胎盘生长因子(PlGF)。运动干预已被证明可以改善孕妇的血管功能,这可能介导血管生成平衡的改善。然而,很少有研究分析久坐和/或身体活动水平与PE的生物标志物之间的关系。本研究的目的是分析客观测量的身体活动和久坐水平与PE风险生物标志物之间的关系。我们假设较高的PA水平与较低的MAP和UtA-PI以及较高的PlGF有关。这是一项辅助研究,从更大的队列(PREVAL研究)中进行方便抽样。采用活动描记仪(GT9X Actigraph)客观测量21名妊娠早期妇女的身体活动和久坐水平。我们测量了PE生物标志物:超声UtA-PI,血清PlGF和数字血压计MAP。根据身体活动和久坐水平将样本分为两组。PE生物标志物组间比较采用t检验或Mann Whitney u检验。显著性水平设为0.05。活性组PlGF比低活性组高57.6 % (P = 0.018)。运动组和低久坐组的UtA-PI和MAP均较低,但差异不显著。中度剧烈运动(MVPA)与PlGF水平相关。因此,我们的研究表明MVPA与PE的生物标志物之间存在合理的联系。
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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 : 2025-09-01 Epub 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
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 : 2025-09-01 Epub 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
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 : 2025-09-01 Epub 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
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 : 2025-09-01 Epub 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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Reproductive biology
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