Protective effect of ginsenoside Rg3 on DBP-induced spermatogenesis injury via the Src/PI3K signaling pathway

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology Pub Date : 2025-09-08 DOI:10.1016/j.reprotox.2025.109047

Huan Li , Hongyan Wang , Xiaolei Xu, Li Qu, Xiuling Sun, Jing Zhang

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Abstract

This study aimed to investigate the protective mechanism of Ginsenoside Rg3 (Rg3) against Di-n-butyl phthalate (DBP) induced spermatogenic damage, focusing on the Src/PI3K/Akt pathway. In vivo experiments demonstrated that Rg3 restored DBP-induced dysregulation of gap junction (GJ) protein connexin 43 (Cx43), improved testicular structure, enhanced sperm parameters (count and motility), and upregulated phosphorylation of Src, PI3K, and Akt (p-Src, p-PI3K, p-Akt) in mice. In vitro studies, using the metabolite of DBP, monobutyl phthalate (MBP), and pathway inhibitors (PP2 for Src and LY294002 for PI3K), further confirmed these effects. Rg3 increased antioxidant enzyme activity, reduced oxidative stress marker MDA, and enhanced the expression of p-Src, p-PI3K, p-Akt, and Cx43 in MBP-treated TM4 Sertoli cells. Inhibitor experiments confirmed that the Src/PI3K pathway mediates Rg3’s protective action. These findings suggest that Rg3 alleviates DBP/MBP-induced male reproductive dysfunction by enhancing antioxidant capacity and reactivating the Src/PI3K/Akt signaling pathway, which helps restore blood-testis barrier (BTB) integrity through Cx43 stabilization. Thus, Rg3 may serve as a potential therapeutic agent for environmental toxicant-related male infertility.

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人参皂苷Rg3通过Src/PI3K信号通路对dbp诱导的精子发生损伤的保护作用

本研究旨在探讨人参皂苷Rg3 （Rg3）对邻苯二甲酸二丁酯（DBP）诱导的生精损伤的保护机制，重点关注Src/PI3K/Akt通路。体内实验表明，Rg3恢复了dbp诱导的小鼠间隙连接蛋白（GJ）连接蛋白43 （Cx43）的失调，改善了睾丸结构，增强了精子参数（数量和活力），上调了Src、PI3K和Akt的磷酸化（p-Src、p-PI3K、p-Akt）。利用DBP代谢物邻苯二甲酸一丁酯（MBP）和途径抑制剂（用于Src的PP2和用于PI3K的LY294002）的体外研究进一步证实了这些作用。Rg3增加抗氧化酶活性，降低氧化应激标志物MDA，增强mbp处理的TM4 Sertoli细胞中p-Src、p-PI3K、p-Akt和Cx43的表达。抑制剂实验证实Src/PI3K通路介导Rg3的保护作用。这些研究结果表明，Rg3通过增强抗氧化能力和重新激活Src/PI3K/Akt信号通路来缓解DBP/ mbp诱导的男性生殖功能障碍，从而通过稳定Cx43帮助恢复血睾丸屏障（BTB）的完整性。因此，Rg3可能作为一种潜在的治疗环境毒性相关性男性不育症的药物。

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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.