Dye intermediates N-phenyl-2-naphthylamine and o-tolidine are novel environmental androgens with reproductive toxicity in male rats

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology Pub Date : 2025-05-29 DOI:10.1016/j.reprotox.2025.108955

Zhiheng Shangguan , Kaiqiang Yang , Qi Pan , Hongli Hu , Pan Wang

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引用次数: 0

Abstract

Endocrine disruptors are environmental chemicals that can interfere with the endocrine system. However, research on endocrine disruptors that interfere with androgen action is still limited. In this study, two new environmental androgens were identified. N-Phenyl-2-naphthylamine (PNA) and o-tolidine are dye intermediates widely used in industry to produce organic pigments. We found that both PNA and o-tolidine activated androgen receptor (AR) transcriptional activity in the luciferase reporter assay and bound to AR-ligand binding domain directly in the surface plasmon resonance analysis. In vivo studies showed that PNA and o-tolidine induced the proliferation of seminal vesicle cells and increased seminal vesicle weight in immature male rats, indicating that these two compounds had androgenic activity in vivo. In addition, in mature male rats, PNA and o-tolidine reduced sperm concentration and motility and increased sperm deformities, and caused atrophy of the seminiferous tubules of the testis and decreased testosterone levels. These results suggest that PNA and o-tolidine are novel environmental androgens, which bind and activate AR and have toxicological effects on male reproductive function.

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染料中间体n -苯基-2-萘胺和邻甲苯胺是雄性大鼠具有生殖毒性的新型环境雄激素

内分泌干扰物是指能够干扰内分泌系统的环境化学物质。然而，对干扰雄激素作用的内分泌干扰物的研究仍然有限。本研究发现了两种新的环境雄激素。n -苯基-2-萘胺（PNA）和邻甲苯胺是工业上广泛用于生产有机颜料的染料中间体。我们发现PNA和邻甲苯胺在荧光素酶报告基因实验中激活了雄激素受体（AR）的转录活性，在表面等离子体共振分析中直接结合到AR配体结合域。体内研究表明，PNA和o-甲苯胺可诱导未成熟雄性大鼠精囊细胞增殖，增加精囊重量，表明这两种化合物在体内具有雄激素活性。此外，在成熟雄性大鼠中，PNA和邻甲苯胺降低了精子浓度和活力，增加了精子畸形，导致睾丸精小管萎缩，睾酮水平下降。这些结果表明PNA和邻甲苯胺是结合和激活AR的新型环境雄激素，对男性生殖功能具有毒理学作用。

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来源期刊

Reproductive toxicology 生物-毒理学

CiteScore

6.50

自引率

3.00%

发文量

131

审稿时长

45 days

期刊介绍： Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine. All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.