首页 > 最新文献

Reproductive biology最新文献

英文 中文
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。
{"title":"Cryptorchidism-induced disruption of TRPM8 expression and calcium signaling in canine testes: A potential mechanism for tumourigenesis","authors":"Anna Gałuszka ,&nbsp;Wojciech Łopuszyński ,&nbsp;Patrycja Kurowska ,&nbsp;Katarzyna Kotarska ,&nbsp;Agnieszka Rak ,&nbsp;Piotr Pawlicki","doi":"10.1016/j.repbio.2025.101052","DOIUrl":"10.1016/j.repbio.2025.101052","url":null,"abstract":"<div><div>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 &lt; 0.01). Western blot analysis revealed a substantial decrease in TRPM8 protein levels (P &lt; 0.001), accompanied by an increase in PKCα and ERK1/2 proteins (P &lt; 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 &lt; 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.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 3","pages":"Article 101052"},"PeriodicalIF":2.5,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703982","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
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。
{"title":"Use of an exogenous DNA-free system to generate MSTN-KO calves by CRISPR/Cas9 and SCNT","authors":"Mariana Suvá ,&nbsp;Juan Ignacio Bastón ,&nbsp;Elisabet Astrid Wiedenmann ,&nbsp;María Belén Pose Ortiz de Rozas ,&nbsp;Roberto Jordán ,&nbsp;Alberto Ghetti ,&nbsp;Diego Luis Viale ,&nbsp;Lucia Natalia Moro ,&nbsp;Gabriel Damián Vichera","doi":"10.1016/j.repbio.2025.101050","DOIUrl":"10.1016/j.repbio.2025.101050","url":null,"abstract":"<div><div>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.</div><div>In the first experiment (E1), we compared the gene editing efficiency of four gRNAs targeting different coding regions of the <em>MSTN</em> 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 <em>MSTN</em> 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-male<sup>ed</sup>) and two edited bovine mesenchymal stem lines (MSC-E2-male<sup>ed</sup> and MSC-E2-fem<sup>ed</sup>) 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-male<sup>ed</sup>, MSC-E2-male<sup>ed</sup> and MSC-E2-fem<sup>ed</sup>, respectively.</div><div>Transfer of 35 MSC-E2-fem<sup>ed</sup> 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.</div><div>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 <em>MSTN</em>-knockout calves. This study provides a foundation for gene editing to improve productive or biomedical traits.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 3","pages":"Article 101050"},"PeriodicalIF":2.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144631122","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
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。
{"title":"Evaluation of the relative gene expression of FGF2, HAS2, BCL2, VEGFA, and PGR in repeat-breeder cows undergoing cyclicity or acyclicity","authors":"Punnawut Yama ,&nbsp;Napatsorn Montha ,&nbsp;Jakree Jitjumnong ,&nbsp;Hien Van Doan ,&nbsp;Nguyen Vu Linh ,&nbsp;Warittha U-krit ,&nbsp;Maslin Osathanunkul ,&nbsp;Raktham Mektrirat ,&nbsp;Julakorn Panatuk ,&nbsp;Payungsuk Intawicha ,&nbsp;Chien-Kai Wang ,&nbsp;Tossapol Moonmanee","doi":"10.1016/j.repbio.2025.101049","DOIUrl":"10.1016/j.repbio.2025.101049","url":null,"abstract":"<div><div>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 [<em>FGF2</em>], hyaluronan synthase 2 [<em>HAS2</em>], B-cell lymphoma 2 [<em>BCL2</em>], vascular endothelial growth factor A [<em>VEGFA</em>], and progesterone receptor [<em>PGR</em>]). The relative expression levels of <em>FGF2</em> mRNA in GCs (0.34-fold and –65.84 %) and <em>PGR</em> mRNA in endometrium (0.09-fold and –90.53 %) were lower (P &lt; 0.05) in acyclic cows relative to cyclic cows. The relative expression levels of <em>HAS2</em> and <em>BCL2</em> 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 <em>VEGFA</em> in the ovary and uterus differed between groups (P &gt; 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.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 3","pages":"Article 101049"},"PeriodicalIF":2.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534363","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
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。
{"title":"The impact of bisphenol A and its analogs on female reproductive health","authors":"Ewelina Trela-Kobędza,&nbsp;Anna Ajduk","doi":"10.1016/j.repbio.2025.101028","DOIUrl":"10.1016/j.repbio.2025.101028","url":null,"abstract":"<div><div>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 <em>in vitro</em> 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.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 3","pages":"Article 101028"},"PeriodicalIF":2.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549559","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
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。
{"title":"The postnatal offspring of finasteride-treated male rats show altered ERα and PCNA expression in the liver","authors":"Agnieszka Kolasa ,&nbsp;Paulina Kur ,&nbsp;Sylwia Rzeszotek ,&nbsp;Marta Grabowska ,&nbsp;Małgorzata Blatkiewicz ,&nbsp;Marika Freus ,&nbsp;Aleksandra Wilk","doi":"10.1016/j.repbio.2025.101044","DOIUrl":"10.1016/j.repbio.2025.101044","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 3","pages":"Article 101044"},"PeriodicalIF":2.5,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534360","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
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 : 2025-06-27 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。
{"title":"Summarizing the human genes and their variants causative of non-obstructive azoospermia uncovered using whole genome/exome sequencing","authors":"Rim Ibrahim,&nbsp;Agnieszka Malcher ,&nbsp;Maciej Kurpisz","doi":"10.1016/j.repbio.2025.101048","DOIUrl":"10.1016/j.repbio.2025.101048","url":null,"abstract":"<div><div>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 <em>NCBI Gene</em> database. The localization/expression of genes were explored using <em>Human Protein Atlas</em> (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.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 3","pages":"Article 101048"},"PeriodicalIF":2.5,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144489559","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
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 : 2025-06-18 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。
{"title":"Trps1 targets Scarb1 to regulate cholesterol acquisition in mouse Leydig cells","authors":"Xiuli Lian ,&nbsp;Zihang Lin ,&nbsp;Weitao Hu ,&nbsp;Zhangting Chen ,&nbsp;Shanshan Luo ,&nbsp;Shumin Liao ,&nbsp;Yue Liu ,&nbsp;Shie Wang ,&nbsp;Jiandong Sun","doi":"10.1016/j.repbio.2025.101046","DOIUrl":"10.1016/j.repbio.2025.101046","url":null,"abstract":"<div><div>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 (<em>Trps1</em>) could inhibit testosterone synthesis in Leydig cells. In the present study, to elucidate the molecular mechanism by which <em>Trps1</em> regulates testosterone synthesis in Leydig cells, differentially expressed genes (DEGs) following <em>Trps1</em> 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 <em>Trps1</em>. 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 (<em>Sf-1</em>) and scavenger receptor class B, member 1 (<em>Scarb1</em>) were up-regulated after <em>Trps1</em> silencing. Knockdown of <em>Sf-1</em> and <em>Scarb1</em> could revert the elevated testosterone and cellular cholesterol levels caused by <em>Trps1</em> deficiency. Moreover, ChIP-seq and CUT&amp;Tag-qPCR demonstrated that the promoter of <em>Scarb1</em> has a binding site for SF-1. The present study revealed that TRPS1 exerts regulatory control over the expression of <em>Scarb1</em> by modulating <em>Sf-1</em> transcriptional activity, thereby enhancing cholesterol level and promoting the synthesis of testosterone in Leydig cells.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 3","pages":"Article 101046"},"PeriodicalIF":2.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306914","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
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 : 2025-06-18 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。
{"title":"Physical activity pattern and Pre-eclampsia risk biomarkers: an observational study","authors":"Ana M. Cagiao ,&nbsp;Pablo Díaz-Brage ,&nbsp;Manuel-Avelino Giráldez ,&nbsp;Marta Torres-Tarrío ,&nbsp;Melissa L. Erickson ,&nbsp;Elvis A. Carnero","doi":"10.1016/j.repbio.2025.101047","DOIUrl":"10.1016/j.repbio.2025.101047","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 3","pages":"Article 101047"},"PeriodicalIF":2.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313287","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
Frequent use of methylphenidate causes reduction in sperm production and sperm quality in adult balb/c mice 频繁使用哌醋甲酯会导致成年balb/c小鼠精子产量和精子质量下降
IF 2.5 3区 生物学 Q3 REPRODUCTIVE BIOLOGY Pub Date : 2025-06-17 DOI: 10.1016/j.repbio.2025.101043
Grasielle Avelar Vieira Rodrigues , Fernanda Carolina Ribeiro Dias , Elizabeth Lopes de Oliveira , Ana Luiza Pereira Martins , Sérgio Luis Pinto da Matta
Methylphenidate is a psychostimulant used mainly in the treatment of attention deficit hyperactivity disorder (ADHD). The present study evaluated the effects of the drug on the testicles of adult mice, through morphological, histometric, hormonal, and sperm evaluations. Twenty-four Balb /c mice were randomly divided into three experimental groups (n = 8). Group 01: control (distilled water); Group 02: 20 mg/kg/day of methylphenidate; Group 03: 40 mg/kg/day of methylphenidate. The treatment caused a reduction in body weight that may indicate toxic effects caused by prolonged use of the drug. Regarding the percentage of tubular components, there was an increase in the percentage of tubule and epithelium, but the percentage of lumen and tunica propria decreased. The diameters of spermatogonia A and Sertoli cells decreased in stage 1 of the cycle. There were reductions in the percentage of lymphatic space, connective tissue, and macrophages, with a consequent reduction in the percentage of intertubules. Methylphenidate treatment during adulthood decreased plasma testosterone concentrations and compromised the spermatogenic process leading to a reduction in the number of spermatids and spermatozoa, sperm production, and sperm transit time in the epididymis. This allowed us to demonstrate that methylphenidate can impair male fertility.
哌醋甲酯是一种精神兴奋剂,主要用于治疗注意缺陷多动障碍(ADHD)。本研究通过形态学、组织计量学、激素和精子评估来评估药物对成年小鼠睾丸的影响。24只Balb /c小鼠随机分为3个实验组(n = 8)。01组:对照(蒸馏水);02组:20 mg/kg/天;03组:40 mg/kg/天。治疗导致体重减轻,这可能表明长期使用该药物引起的毒性作用。在小管成分的百分比上,小管和上皮的百分比增加,而管腔和固有膜的百分比下降。精原细胞A和支持细胞直径在周期的第1阶段减小。淋巴间隙、结缔组织和巨噬细胞的百分比减少,随之而来的是小管间的百分比减少。成年期的哌醋甲酯治疗降低了血浆睾酮浓度,损害了生精过程,导致精子数量和精子数量减少,精子产量减少,精子在附睾中的转运时间减少。这使我们能够证明哌甲酯会损害男性的生育能力。
{"title":"Frequent use of methylphenidate causes reduction in sperm production and sperm quality in adult balb/c mice","authors":"Grasielle Avelar Vieira Rodrigues ,&nbsp;Fernanda Carolina Ribeiro Dias ,&nbsp;Elizabeth Lopes de Oliveira ,&nbsp;Ana Luiza Pereira Martins ,&nbsp;Sérgio Luis Pinto da Matta","doi":"10.1016/j.repbio.2025.101043","DOIUrl":"10.1016/j.repbio.2025.101043","url":null,"abstract":"<div><div>Methylphenidate is a psychostimulant used mainly in the treatment of attention deficit hyperactivity disorder (ADHD). The present study evaluated the effects of the drug on the testicles of adult mice, through morphological, histometric, hormonal, and sperm evaluations. Twenty-four Balb /c mice were randomly divided into three experimental groups (n = 8). Group 01: control (distilled water); Group 02: 20 mg/kg/day of methylphenidate; Group 03: 40 mg/kg/day of methylphenidate. The treatment caused a reduction in body weight that may indicate toxic effects caused by prolonged use of the drug. Regarding the percentage of tubular components, there was an increase in the percentage of tubule and epithelium, but the percentage of lumen and tunica propria decreased. The diameters of spermatogonia A and Sertoli cells decreased in stage 1 of the cycle. There were reductions in the percentage of lymphatic space, connective tissue, and macrophages, with a consequent reduction in the percentage of intertubules. Methylphenidate treatment during adulthood decreased plasma testosterone concentrations and compromised the spermatogenic process leading to a reduction in the number of spermatids and spermatozoa, sperm production, and sperm transit time in the epididymis. This allowed us to demonstrate that methylphenidate can impair male fertility.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 3","pages":"Article 101043"},"PeriodicalIF":2.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296780","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
Morpho-functional and biochemical improvements in ram spermatozoa following intraepididymal platelet-rich plasma administration 附睾内富血小板血浆对公羊精子形态功能和生化的改善
IF 2.5 3区 生物学 Q3 REPRODUCTIVE BIOLOGY Pub Date : 2025-06-11 DOI: 10.1016/j.repbio.2025.101045
Serap Dayan Cinkara , Nida Badıllı , İbrahim Halil Güngör , Aslıhan Çakır Cihangiroğlu , Tutku Can Acısu , Görkem Kırmızıkaya Özmen , Gözde Arkalı , Şeyma Özer Kaya , Mustafa Sönmez , Seyfettin Gür , Abdurrauf Yüce , Ökkeş Yılmaz , Gaffari Türk
This study evaluated the effects of intraepididymal platelet-rich plasma (PRP) administration on sperm morpho-functional characteristics and biochemical profiles in rams. Twelve healthy one-year-old Akkaraman rams were randomly assigned to control (0.9 % NaCl) and PRP (0.2 mL/per epididymis; ∼150–200 ×10⁶ platelets) groups, with six biweekly injections. Semen was collected biweekly and subjected to routine spermatological, flow-cytometric and biochemical assessments. PRP treatment significantly enhanced plasma membrane integrity (P < 0.001), total and rapid motility (P < 0.05), and kinematic parameters including VCL (P < 0.05), VSL, VAP, LIN, and WOB (P < 0.01). Significant reductions were observed in head and total abnormalities (P < 0.001), static spermatozoa (P < 0.05), ALH, and BCF (P < 0.05). Flow-cytometric analyses revealed increased proportions of sperm with high mitochondrial activity (P < 0.01), along with decreased acrosomal damage (P < 0.05) and apoptotic spermatozoa (P < 0.001). Biochemical assays demonstrated a marked reduction in malondialdehyde level (P < 0.001) and increased glutathione level, and glutathione-peroxidase and catalase activities (P < 0.01), indicating improved oxidative status. Although a 10.05 % increase in cholesterol level was observed following PRP administration, the change was not statistically significant. However, PRP significantly elevated margaric (C17:0) and stearic (C18:0) acids (P < 0.05–0.01), vaccenic (C18:1n7) and nervonic (C24:1) acids (P < 0.001), and α-linoleic (C18:3n3) and docosapentaenoic (C22:5n3) acids (P < 0.001). These findings suggest that epididymal PRP administration improves sperm quality via enhanced antioxidant capacity, mitochondrial function, and lipid remodeling.
本研究评价了附睾富血小板血浆(PRP)给药对公羊精子形态功能特征和生化特征的影响。12只健康一岁阿卡拉曼公羊随机分为对照组(0.9 % NaCl)和PRP组(0.2 mL/ /附睾;~ 150-200 ×10 26血小板)组,每两周注射6次。每两周采集一次精液,并进行常规精子学、流式细胞术和生化评估。PRP治疗显著提高了质膜完整性(P <; 0.001)、总运动和快速运动(P <; 0.05)和运动学参数,包括VCL (P <; 0.05)、VSL、VAP、LIN和WOB (P <; 0.01)。头部和总异常(P <; 0.001)、静态精子(P <; 0.05)、ALH和BCF (P <; 0.05)均显著降低。流式细胞术分析显示,高线粒体活性精子的比例增加(P <; 0.01),顶体损伤(P <; 0.05)和凋亡精子(P <; 0.001)减少。生化分析显示丙二醛水平显著降低(P <; 0.001),谷胱甘肽水平、谷胱甘肽过氧化物酶和谷胱甘肽过氧化氢酶活性显著增加(P <; 0.01),表明氧化状态得到改善。虽然在服用PRP后观察到胆固醇水平升高10.05 %,但变化无统计学意义。然而,PRP显著提高了人造脂肪酸(C17:0)和硬脂酸(C18:0)酸(P <; 0.05-0.01)、异丙酸(C18:1n7)和神经酸(C24:1)酸(P <; 0.001),以及α-亚油酸(C18:3n3)和二十碳五烯酸(C22:5n3)酸(P <; 0.001)。这些发现表明附睾PRP通过增强抗氧化能力、线粒体功能和脂质重塑来改善精子质量。
{"title":"Morpho-functional and biochemical improvements in ram spermatozoa following intraepididymal platelet-rich plasma administration","authors":"Serap Dayan Cinkara ,&nbsp;Nida Badıllı ,&nbsp;İbrahim Halil Güngör ,&nbsp;Aslıhan Çakır Cihangiroğlu ,&nbsp;Tutku Can Acısu ,&nbsp;Görkem Kırmızıkaya Özmen ,&nbsp;Gözde Arkalı ,&nbsp;Şeyma Özer Kaya ,&nbsp;Mustafa Sönmez ,&nbsp;Seyfettin Gür ,&nbsp;Abdurrauf Yüce ,&nbsp;Ökkeş Yılmaz ,&nbsp;Gaffari Türk","doi":"10.1016/j.repbio.2025.101045","DOIUrl":"10.1016/j.repbio.2025.101045","url":null,"abstract":"<div><div>This study evaluated the effects of intraepididymal platelet-rich plasma (PRP) administration on sperm morpho-functional characteristics and biochemical profiles in rams. Twelve healthy one-year-old Akkaraman rams were randomly assigned to control (0.9 % NaCl) and PRP (0.2 mL/per epididymis; ∼150–200 ×10⁶ platelets) groups, with six biweekly injections. Semen was collected biweekly and subjected to routine spermatological, flow-cytometric and biochemical assessments. PRP treatment significantly enhanced plasma membrane integrity (<em>P</em> &lt; 0.001), total and rapid motility (<em>P</em> &lt; 0.05), and kinematic parameters including VCL (<em>P</em> &lt; 0.05), VSL, VAP, LIN, and WOB (<em>P</em> &lt; 0.01). Significant reductions were observed in head and total abnormalities (<em>P</em> &lt; 0.001), static spermatozoa (<em>P</em> &lt; 0.05), ALH, and BCF (<em>P</em> &lt; 0.05). Flow-cytometric analyses revealed increased proportions of sperm with high mitochondrial activity (<em>P</em> &lt; 0.01), along with decreased acrosomal damage (<em>P</em> &lt; 0.05) and apoptotic spermatozoa (<em>P</em> &lt; 0.001). Biochemical assays demonstrated a marked reduction in malondialdehyde level (<em>P</em> &lt; 0.001) and increased glutathione level, and glutathione-peroxidase and catalase activities (<em>P</em> &lt; 0.01), indicating improved oxidative status. Although a 10.05 % increase in cholesterol level was observed following <em>P</em>RP administration, the change was not statistically significant. However, PRP significantly elevated margaric (C17:0) and stearic (C18:0) acids (<em>P</em> &lt; 0.05–0.01), vaccenic (C18:1n7) and nervonic (C24:1) acids (<em>P</em> &lt; 0.001), and α-linoleic (C18:3n3) and docosapentaenoic (C22:5n3) acids (<em>P</em> &lt; 0.001). These findings suggest that epididymal PRP administration improves sperm quality via enhanced antioxidant capacity, mitochondrial function, and lipid remodeling.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 3","pages":"Article 101045"},"PeriodicalIF":2.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144262494","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
期刊
Reproductive biology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1