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Scriptaid is a prospective agent for improving human asthenozoospermic sample quality and fertilization rate in vitro. Scriptaid 是一种可改善人类无精子样本质量和体外受精率的前瞻性药物。
Pub Date : 2024-09-01 Epub Date: 2024-06-11 DOI: 10.4103/aja202416
Yi-Ting Yang, Bin Yan, Li-Na Guo, Miao Liu, Yu-Hua Li, Zhi-Yu Shao, Hua Diao, Su-Ying Liu, He-Guo Yu

Abstract: Male infertility is a global issue caused by poor sperm quality, particularly motility. Enhancement of the sperm quality may improve the fertilization rate in assisted reproductive technology (ART) treatment. Scriptaid, with a novel human sperm motility-stimulating activity, has been investigated as a prospective agent for improving sperm quality and fertilization rate in ART. We evaluated the effects of Scriptaid on asthenozoospermic (AZS) semen, including its impact on motility stimulation and protective effects on cryopreservation and duration of motility, by computer-aided sperm analysis (CASA). Sperm quality improvement by Scriptaid was characterized by increased hyaluronan-binding activity, tyrosine phosphorylation, adenosine triphosphate (ATP) concentration, mitochondrial membrane potential, and an ameliorated AZS fertilization rate in clinical intracytoplasmic sperm injection (ICSI) experiments. Furthermore, our identification of active Scriptaid analogs and different metabolites induced by Scriptaid in spermatozoa lays a solid foundation for the future biomechanical exploration of sperm function. In summary, Scriptaid is a potential candidate for the treatment of male infertility in vitro as it improves sperm quality, prolongs sperm viability, and increases the fertilization rate.

摘要:男性不育是一个全球性问题,其原因是精子质量差,尤其是活力差。提高精子质量可提高辅助生殖技术(ART)治疗中的受精率。Scriptaid具有新型人类精子活力刺激活性,已被研究作为提高精子质量和辅助生殖技术受精率的前瞻性药物。我们通过计算机辅助精子分析(CASA)评估了Sriptaid对无精子症(AZS)精液的影响,包括对活力刺激的影响以及对冷冻保存和活力持续时间的保护作用。通过提高透明质酸结合活性、酪氨酸磷酸化、三磷酸腺苷(ATP)浓度、线粒体膜电位,以及在临床卵胞浆内单精子注射(ICSI)实验中改善 AZS 受精率,Scriptaid 可以提高精子质量。此外,我们还鉴定了精子中的活性 Scriptaid 类似物和 Scriptaid 诱导的不同代谢物,这为今后从生物力学角度探索精子功能奠定了坚实的基础。总之,Sriptaid 是体外治疗男性不育症的潜在候选药物,因为它能改善精子质量、延长精子存活时间并提高受精率。
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引用次数: 0
Sperm RNA quantity and PRM1, PRM2, and TH2B transcript levels reflect sperm characteristics and early embryonic development. 精子 RNA 数量以及 PRM1、PRM2 和 TH2B 转录本水平反映了精子的特征和早期胚胎发育。
Pub Date : 2024-08-27 DOI: 10.4103/aja202452
Bilge Ozsait-Selcuk, Sibel Bulgurcuoglu-Kuran, Dilek Sever-Kaya, Neslihan Coban, Gulsen Aktan, Ates Kadioglu

Abstract: Spermatozoa have a highly complex RNA profile. Several of these transcripts are suggested as biomarkers for male infertility and contribute to early development. To analyze the differences between sperm RNA quantity and expression of protamine (PRM1 and PRM2) and testis-specific histone 2B (TH2B) genes, spermatozoa from 33 patients who enrolled in assisted reproduction treatment (ART) program were analyzed. Sperm RNA of teratozoospermic (T), oligoteratozoospermic (OT), and normozoospermic (N) samples was extracted, and the differences in transcript levels among the study groups were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The correlations of total RNA per spermatozoon and the expression of the transcripts were evaluated in relation to sperm characteristics and preimplantation embryo development. The mean (±standard deviation) RNA amount per spermatozoon was 28.48 (±23.03) femtogram in the overall group and was significantly higher in the OT group than that in N and T groups. Total sperm RNA and gene expression of PRM1 and PRM2 genes were related to preimplantation embryo development and developmental arrest. Specific sperm characteristics were correlated with the expressions of PRM1, PRM2, or TH2B genes. We conclude that the sperm RNA amount and composition are important factors and might influence early embryonic development and also differ in different cases of male infertility.

摘要:精子具有高度复杂的 RNA 图谱。其中一些转录本被认为是男性不育症的生物标志物,并有助于早期发育。为了分析精子RNA数量与原胺(PRM1和PRM2)和睾丸特异性组蛋白2B(TH2B)基因表达之间的差异,研究人员对33名参加辅助生殖治疗(ART)项目的患者的精子进行了分析。提取了畸形精子症(T)、少精子症(OT)和正常精子症(N)样本的精子 RNA,并通过实时定量聚合酶链反应(qRT-PCR)分析了研究组间转录水平的差异。评估了每个精子的总 RNA 和转录本表达与精子特征和植入前胚胎发育的相关性。全组每个精子的平均(±标准差)RNA量为28.48(±23.03)毫微克,OT组明显高于N组和T组。精子总RNA以及PRM1和PRM2基因的表达与植入前胚胎发育和发育停滞有关。特定的精子特征与 PRM1、PRM2 或 TH2B 基因的表达相关。我们的结论是,精子RNA的数量和组成是重要因素,可能会影响早期胚胎发育,而且在不同的男性不育症病例中也存在差异。
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引用次数: 0
Intralesional and topical treatments for Peyronie's disease: a narrative review of current knowledge. 佩罗尼氏病的内服和外用疗法:现有知识综述。
Pub Date : 2024-08-23 DOI: 10.4103/aja202460
Antonio Minore, Loris Cacciatore, Fabrizio Presicce, Andrea Iannuzzi, Antonio Testa, Gianluigi Raso, Rocco Papalia, Marco Martini, Roberto Mario Scarpa, Francesco Esperto

Abstract: Peyronie's disease (PD) presents a multifaceted challenge in contemporary urological practice, marked by penile deformity, pain, and the potential for erectile dysfunction. We meticulously explored the existing literature of intralesional/topical interventions, aiming to provide clinicians with a nuanced understanding of available options for comprehensive PD management. To conduct this review, we performed a systematic search using the PubMed, Scopus, and ScienceDirect databases, including the keywords of combination of the "Peyronie's disease/plastic induration of the penis (PIP) and intralesional/topical treatments". The study selection was based on adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, resulting in the inclusion of 16 articles. We delve into the effectiveness and safety profiles of collagenase Clostridium histolyticum (CCH), interferon, platelet-rich plasma (PRP), hyaluronic acid, botulinum toxin, stem cell, extracorporeal shock wave therapy (ESWT), and traction therapy, assessing their impact on penile curvature, length improvement, and patient-reported symptoms and outcomes. The best options evaluated are intralesional injections of CCH and penile traction devices, alone or in combination. Despite PD remains a challenge for urologists, the objective of this review is to contribute to the evolving landscape of PD management, fostering informed decision-making, and personalized care for individuals grappling with this challenging condition.

摘要:佩罗尼氏病(Peyronie's disease,PD)是当代泌尿外科临床中的一项多方面挑战,主要表现为阴茎畸形、疼痛和潜在的勃起功能障碍。我们仔细研究了现有的腔内/局部干预文献,旨在让临床医生对综合治疗 PD 的可用方案有一个细致入微的了解。为了进行此次综述,我们使用 PubMed、Scopus 和 ScienceDirect 数据库进行了系统性检索,其中包括 "佩罗尼氏病/阴茎整形性萎缩(PIP)和腔内/局部治疗 "的组合关键词。根据系统综述和元分析首选报告项目(PRISMA)指南对研究进行了筛选,最终纳入了 16 篇文章。我们深入研究了胶原酶溶解梭菌(CCH)、干扰素、富血小板血浆(PRP)、透明质酸、肉毒杆菌毒素、干细胞、体外冲击波疗法(ESWT)和牵引疗法的有效性和安全性,评估了它们对阴茎弯曲、长度改善以及患者报告症状和结果的影响。目前评估的最佳方案是鞘内注射 CCH 和阴茎牵引装置(单独使用或联合使用)。尽管阴茎短小症对泌尿科医生来说仍是一项挑战,但本综述的目的是为不断发展的阴茎短小症管理做出贡献,促进知情决策,并为应对这一挑战性疾病的患者提供个性化护理。
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引用次数: 0
Association of redundant foreskin with sexual dysfunction: a cross-sectional study from 5700 participants. 多余包皮与性功能障碍的关系:对 5700 名参与者进行的横断面研究。
Pub Date : 2024-08-20 DOI: 10.4103/aja202461
Yuan-Qi Zhao, Nian Li, Xiao-Hua Jiang, Yang-Yang Wan, Bo Xu, Xue-Chun Hu, Yi-Fu Hou, Ji-Yan Li, Shun Bai

A previous study showed that the length of the foreskin plays a role in the risk of sexually transmitted infections and chronic prostatitis, which can lead to poor quality of sexual life. Here, the association between foreskin length and sexual dysfunction was evaluated. A total of 5700 participants were recruited from the andrology clinic at The First Affiliated Hospital of University of Science and Technology of China (Hefei, China). Clinical characteristics, including foreskin length, were collected, and sexual function was assessed by the International Index of Erectile Function-5 (IIEF-5) and Premature Ejaculation Diagnostic Tool (PEDT) questionnaires. Men with sexual dysfunction were more likely to have redundant foreskin than men without sexual dysfunction. Among the 2721 erectile dysfunction (ED) patients and 1064 premature ejaculation (PE) patients, 301 (11.1%) ED patients and 135 (12.7%) PE patients had redundant foreskin, respectively. Men in the PE group were more likely to have redundant foreskin than men in the non-PE group (P = 0.004). Logistic regression analyses revealed that the presence of redundant foreskin was associated with increased odds of moderate/severe ED (adjusted odds ratio [aOR] = 1.31, adjusted P = 0.04), moderate PE (aOR = 1.38, adjusted P = 0.02), and probable PE (aOR = 1.37, adjusted P = 0.03) after adjusting for confounding variables. Our study revealed a positive correlation between the presence of redundant foreskin and the risk of sexual dysfunction, especially in PE patients. Assessment of the length of the foreskin during routine clinical diagnosis may provide information for patients with sexual dysfunction.

先前的一项研究表明,包皮的长度对性传播感染和慢性前列腺炎的风险有一定影响,会导致性生活质量低下。本研究评估了包皮长度与性功能障碍之间的关系。中国科学技术大学第一附属医院(中国合肥)泌尿外科门诊共招募了 5700 名参与者。研究人员收集了包括包皮长度在内的临床特征,并通过国际勃起功能指数-5(IIEF-5)和早泄诊断工具(PEDT)问卷评估了性功能。与没有性功能障碍的男性相比,有性功能障碍的男性更有可能有多余的包皮。在2721名勃起功能障碍(ED)患者和1064名早泄(PE)患者中,分别有301名(11.1%)ED患者和135名(12.7%)PE患者有多余包皮。PE组男性比非PE组男性更容易出现包皮过长(P = 0.004)。逻辑回归分析显示,在调整了混杂变量后,存在多余包皮与中度/重度ED(调整后的几率比[aOR] = 1.31,调整后的P = 0.04)、中度PE(aOR = 1.38,调整后的P = 0.02)和可能PE(aOR = 1.37,调整后的P = 0.03)的几率增加有关。我们的研究显示,多余包皮的存在与性功能障碍的风险呈正相关,尤其是在 PE 患者中。在常规临床诊断中评估包皮长度可为性功能障碍患者提供信息。
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引用次数: 0
Gene regulation and signaling transduction in mediating the self-renewal, differentiation, and apoptosis of spermatogonial stem cells. 介导精原干细胞自我更新、分化和凋亡的基因调控和信号转导。
Pub Date : 2024-08-20 DOI: 10.4103/aja202464
Cai-Mei He, Dong Zhang, Zuping He

Infertility has become one of the most serious diseases worldwide, and 50% of this disease can be attributed to male-related factors. Spermatogenesis, by definition, is a complex process by which spermatogonial stem cells (SSCs) self-renew to maintain stem cell population within the testes and differentiate into mature spermatids. It is of great significance to uncover gene regulation and signaling pathways that are involved in the fate determinations of SSCs with aims to better understand molecular mechanisms underlying human spermatogenesis and identify novel targets for gene therapy of male infertility. Significant achievement has recently been made in demonstrating the signaling molecules and pathways mediating the fate decisions of mammalian SSCs. In this review, we address key gene regulation and crucial signaling transduction pathways in controlling the self-renewal, differentiation, and apoptosis of SSCs, and we illustrate the networks of genes and signaling pathways in SSC fate determinations. We also highlight perspectives and future directions in SSC regulation by genes and their signaling pathways. This review could provide novel insights into the genetic regulation of normal and abnormal spermatogenesis and offer molecular targets to develop new approaches for gene therapy of male infertility.

不育症已成为全球最严重的疾病之一,其中50%可归因于与男性有关的因素。根据定义,精子发生是精原干细胞(SSC)自我更新以维持睾丸内干细胞群并分化为成熟精子的复杂过程。揭示参与精原干细胞命运决定的基因调控和信号通路,对于更好地理解人类精子发生的分子机制和确定男性不育症基因治疗的新靶点具有重要意义。近来,在证明介导哺乳动物造精细胞命运决定的信号分子和通路方面取得了重大成就。在这篇综述中,我们探讨了控制造血干细胞自我更新、分化和凋亡的关键基因调控和重要信号转导途径,并阐述了造血干细胞命运决定过程中的基因和信号途径网络。我们还强调了基因及其信号通路对造血干细胞调控的前景和未来方向。本综述可为正常和异常精子发生的基因调控提供新的见解,并为开发男性不育基因治疗的新方法提供分子靶点。
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引用次数: 0
Divergences in neuroendocrine prostate cancer frequency as recognized by anatomic pathologists, clinicians, and basic scientists. 解剖病理学家、临床医生和基础科学家认识到的神经内分泌前列腺癌频率差异。
Pub Date : 2024-08-20 DOI: 10.4103/aja202467
Kenneth A Iczkowski, Mamta Parikh
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引用次数: 0
Role of pericytes in regulating penile angiogenesis and nerve regeneration. 周细胞在调节阴茎血管生成和神经再生中的作用
Pub Date : 2024-08-20 DOI: 10.4103/aja202455
Guo Nan Yin, Ji-Kan Ryu

Pericytes are multifunctional mural cells that surround the abluminal wall of endothelial cells and are associated with vascular development, vascular permeability, and angiogenesis. Additionally, pericytes demonstrate stem cell-like properties and contribute to neuroinflammatory processes. Pericytes have been extensively studied in the central nervous system. However, specific mechanisms underlying its involvement in various physiological and pathological conditions, especially in erectile dysfunction (ED), remain poorly understood. Advancements in in vitro and in vitro techniques, such as single-cell RNA sequencing, are expanding our understanding of pericytes. Recent studies have shown that pericyte dysfunction is considered an important factor in the pathogenesis of vascular and neurological ED. Therefore, this study aims to analyze the specific role of pericytes in ED, focusing on diabetic and neurogenic ED. This article provides a comprehensive review of research findings on PubMed from 2000 to 2023, concerning pericyte dysfunction in the process of ED, offering valuable insights, and suggesting directions for further research.

周细胞是围绕内皮细胞腔壁的多功能壁细胞,与血管发育、血管通透性和血管生成有关。此外,周细胞还具有类似干细胞的特性,有助于神经炎症过程。对中枢神经系统中的周细胞进行了广泛的研究。然而,人们对其参与各种生理和病理状况(尤其是勃起功能障碍(ED))的具体机制仍然知之甚少。体外和体外技术(如单细胞 RNA 测序)的进步正在扩大我们对周细胞的了解。最近的研究表明,周细胞功能障碍被认为是血管性和神经性 ED 发病机制中的一个重要因素。因此,本研究旨在分析周细胞在 ED 中的特殊作用,重点关注糖尿病和神经源性 ED。本文全面综述了2000年至2023年PubMed上有关ED过程中包膜细胞功能障碍的研究成果,提出了有价值的见解,并为进一步的研究指明了方向。
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引用次数: 0
Technologies to improve sperm retrieval in men undergoing micro-TESE for NOA. 改善因无脑畸形而接受显微取精术(micro-TESE)的男性取精情况的技术。
Pub Date : 2024-08-16 DOI: 10.4103/aja202450
Parviz K Kavoussi, Widi Atmoko, Germar-Michael Pinggera

Nonobstructive azoospermia (NOA) is considered the most challenging clinical scenario for infertile men and current treatments leave many men unsuccessful at being able to achieve a pregnancy with their partner using their own sperm. Microdissection testicular sperm extraction (micro-TESE) is the choice for men with NOA desiring to father children with their own gametes. Micro-TESE results in the highest numbers of sperm cells retrieved for use with in vitro fertilization/intracytoplasmic sperm injection. With suboptimal micro-TESE success rates of sperm retrieval and then pregnancy and live birth using the retrieved sperm with in vitro fertilization/intracytoplasmic sperm injection, advances to improve outcomes are necessary. This article comprehensively reviews the technologies investigated to date to improve the outcomes for men undergoing micro-TESE.

非梗阻性无精子症(NOA)被认为是不育男性面临的最具挑战性的临床情况,目前的治疗方法使许多男性无法使用自己的精子与伴侣成功受孕。显微解剖睾丸取精术(micro-TESE)是希望用自己的配子生儿育女的无精症男性的选择。显微睾丸取精术提取的精子细胞数量最多,可用于体外受精/卵胞浆内单精子注射。由于显微取精术(Micro-TESE)的取精成功率并不理想,而且使用取回的精子进行体外受精/卵胞浆内单精子注射后还会导致怀孕和活产,因此有必要取得进展以改善结果。本文全面回顾了迄今为止为改善男性显微取精术(micro-TESE)效果而研究的技术。
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引用次数: 0
In vitro effects of antidepressants on human sperm function. 抗抑郁药对人类精子功能的体外影响。
Pub Date : 2024-08-13 DOI: 10.4103/aja202459
Rita António Santos, Ana Paula Sousa, Teresa Almeida-Santos, João Ramalho-Santos, Renata Santos Tavares

Depression currently affects about 280 million people worldwide and its prevalence has been increasing dramatically, especially among the young and people of reproductive age, which consequently leads to an increase in antidepressant consumption. Antidepressants are associated with sexual dysfunction in both men and women; however, their role in male fertility has been scarcely studied. Fluoxetine and sertraline, two serotonin reuptake inhibitors (SSRIs), are among the most prescribed antidepressants worldwide. To determine their possible effects, human sperm cells were exposed to either sertraline or fluoxetine at concentrations previously found in blood and seminal fluid of patients undergoing treatment. Spermatozoa were incubated for up to 24 h at 37°C and 5% CO2, and important functional parameters such as sperm motility, viability, mitochondrial membrane potential, cellular reactive oxygen species (ROS) production, chromatin/DNA integrity, acrosome status, and tyrosine phosphorylation were assessed. At low levels, fluoxetine consistently decreased progressive motility throughout time while promoting fluctuations in ROS levels and sperm capacitation. Nevertheless, it did not affect viability, mitochondrial membrane potential, acrosome reaction nor chromatin/DNA integrity. Sertraline, on the other hand, had little to nonsignificant impact at low doses, but affected almost all tested parameters at supratherapeutic concentrations. Altogether, our results suggest that both antidepressants may impair sperm function, possibly through different mechanisms of action, but fluoxetine is the only exhibiting mild negative effects at doses found in vivo.

目前,全世界约有 2.8 亿人受到抑郁症的影响,其发病率正在急剧上升,尤其是在年轻人和育龄人群中,这也导致了抗抑郁药物用量的增加。抗抑郁药与男性和女性的性功能障碍都有关联,但它们对男性生育力的影响却鲜有研究。氟西汀和舍曲林这两种血清素再摄取抑制剂(SSRIs)是全球处方量最多的抗抑郁药。为了确定这两种药物可能产生的影响,我们将人类精子细胞暴露于舍曲林或氟西汀中,其浓度以前曾在接受治疗的患者的血液和精液中发现过。精子在 37°C 和 5% CO2 条件下培养长达 24 小时,并对精子的活力、存活率、线粒体膜电位、细胞活性氧(ROS)产生、染色质/DNA 完整性、顶体状态和酪氨酸磷酸化等重要功能参数进行评估。在低浓度下,氟西汀会持续降低精子的运动能力,同时促进 ROS 水平的波动和精子获能。然而,氟西汀不会影响精子活力、线粒体膜电位、顶体反应或染色质/DNA完整性。另一方面,舍曲林在低剂量时几乎没有影响,但在超治疗浓度时几乎影响所有测试参数。总之,我们的研究结果表明,这两种抗抑郁药可能会通过不同的作用机制损害精子功能,但在体内发现的剂量下,氟西汀是唯一表现出轻微负面影响的药物。
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引用次数: 0
A behind-the-scenes role of BDNF in the survival and differentiation of spermatogonia. BDNF在精原细胞存活和分化过程中的幕后作用
Pub Date : 2024-08-13 DOI: 10.4103/aja202457
Shin-Ichi Tomizawa, Kazushige Kuroha, Michio Ono, Kuniko Nakajima, Kazuyuki Ohbo

Mouse spermatogenesis entails the maintenance and self-renewal of spermatogonial stem cells (SSCs), which require a complex web-like signaling network transduced by various cytokines. Although brain-derived neurotrophic factor (BDNF) is expressed in Sertoli cells in the testis, and its receptor tropomyosin receptor kinase B (TrkB) is expressed in the spermatogonial population containing SSCs, potential functions of BDNF for spermatogenesis have not been uncovered. Here, we generate BDNF conditional knockout mice and find that BDNF is dispensable for in vivo spermatogenesis and fertility. However, in vitro, we reveal that BDNF-deficient germline stem cells (GSCs) exhibit growth potential not only in the absence of glial cell line-derived neurotrophic factor (GDNF), a master regulator for GSC proliferation, but also in the absence of other factors, including epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and insulin. GSCs grown without these factors are prone to differentiation, yet they maintain expression of promyelocytic leukemia zinc finger (Plzf), an undifferentiated spermatogonial marker. Inhibition of phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK), and Src pathways all interfere with the growth of BDNF-deficient GSCs. Thus, our findings suggest a role for BDNF in maintaining the undifferentiated state of spermatogonia, particularly in situations where there is a shortage of growth factors.

小鼠精子发生需要精原干细胞(SSC)的维持和自我更新,这需要由各种细胞因子转导的复杂的网状信号网络。虽然脑源性神经营养因子(BDNF)在睾丸的Sertoli细胞中表达,其受体肌球蛋白受体激酶B(TrkB)在含有SSCs的精原细胞群中表达,但BDNF对精子发生的潜在功能尚未被发现。在这里,我们产生了 BDNF 条件性基因敲除小鼠,并发现 BDNF 对于体内精子发生和生育能力是不可或缺的。然而,在体外,我们发现BDNF缺陷的生殖干细胞(GSCs)不仅在缺乏神经胶质细胞系衍生神经营养因子(GDNF)(GSC增殖的主要调节因子)的情况下表现出生长潜力,而且在缺乏其他因子(包括表皮生长因子(EGF)、碱性成纤维细胞生长因子(bFGF)和胰岛素)的情况下也表现出生长潜力。在没有这些因子的情况下生长的 GSC 很容易分化,但它们仍能保持早幼粒细胞白血病锌指(Plzf)的表达,这是一种未分化的精原细胞标记。磷酸肌酸3-激酶(PI3K)、丝裂原活化蛋白激酶(MAPK)/细胞外信号调节激酶(ERK)和Src通路的抑制都会干扰BDNF缺陷型GSCs的生长。因此,我们的研究结果表明,BDNF 在维持精原细胞的未分化状态方面发挥作用,尤其是在缺乏生长因子的情况下。
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引用次数: 0
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Asian journal of andrology
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