关键词: Androgen Receptor GBH Leydig cell Nitric oxide P53 Testes

Mesh : Animals Male Glyphosate Spermatogenesis / drug effects Rats, Wistar Testis / drug effects pathology Herbicides / toxicity Glycine / analogs & derivatives toxicity administration & dosage Rats Oxidative Stress / drug effects Tumor Suppressor Protein p53 / metabolism Endocrine Disruptors / toxicity Receptors, Androgen / metabolism Testosterone Leydig Cells / drug effects metabolism pathology

来  源:   DOI:10.1016/j.repbio.2024.100865

Abstract:
Glyphosate is an endocrine disruptor and can act on the activity of certain enzymes of metabolism subsequently altering some functions such as reproduction. The goal of the present study is to evaluate the involvement of glyphosate based-herbicide (GBH) in spermatogenesis disruption and to investigate which cells of the adult Wistar rat testis are most affected by short-term exposure to GBH. Treated groups received a diluted solution of GBH orally for 21 days (D1: 102.5 mg/Kg; D2: 200 mg/Kg; D3: 400 mg/Kg). The control group (C) received water in the same manner. Hormone levels, oxidative stress markers were evaluated, histological and morphometric analysis were performed, AR and p53 expression was conducted. Seminiferious epithelium sloughing associated to erosion of Sertoli and spermatogonia from the basement of the seminiferous tubules, with intraluminal exfoliated cells among with immature spermatids were observed. A significant change in morphometric measurement and significant decrease in AR expression in Sertoli cells were noted for all treated groups. A significant increase in NO level and p53 expression in Leydig cells were showed for animals treated with 200 and 400 mg/kg BW/day. These data demonstrate that short-term exposure to high doses of GBH has led to a disruption of certain parameters that could disturb spermatogenesis. The treatment showed that both Leydig and Sertoli cells are affected in the same manner by GBH, the activation of p53 expression in both Leydig cells and peritubular myloid cells nuclei, and the reduction in AR expression in Sertoli cells, which resulted in important testicular damage.
摘要:
草甘膦是一种内分泌干扰物,可以作用于某些代谢酶的活性,随后改变某些功能,如繁殖。本研究的目的是评估基于草甘膦的除草剂(GBH)在精子发生破坏中的参与,并研究成年Wistar大鼠睾丸的哪些细胞受短期暴露于GBH的影响最大。处理组口服GBH的稀释溶液21天(D1:102.5mg/Kg;D2:200mg/Kg;D3:400mg/Kg)。对照组(C)以相同方式接受水。激素水平,氧化应激标志物进行了评估,进行组织学和形态分析,进行AR和p53表达。与生精小管基底的Sertoli和精原细胞侵蚀有关的生精病上皮脱落,观察到未成熟精子细胞中的腔内脱落细胞。所有处理组均注意到形态测量的显著变化和支持细胞中AR表达的显著降低。对于用200和400mg/kgBW/天处理的动物,显示Leydig细胞中NO水平和p53表达的显著增加。这些数据表明,短期暴露于高剂量的GBH会导致某些参数的破坏,这可能会干扰精子发生。治疗表明Leydig和Sertoli细胞都以相同的方式受到GBH的影响,睾丸间质细胞和肾小管周围菌样细胞核中p53表达的激活,和睾丸支持细胞中AR表达的减少,导致重要的睾丸损伤.
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