Huan Li , Hongyan Wang , Xiaolei Xu, Li Qu, Xiuling Sun, Jing Zhang
{"title":"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","authors":"Huan Li , Hongyan Wang , Xiaolei Xu, Li Qu, Xiuling Sun, Jing Zhang","doi":"10.1016/j.reprotox.2025.109047","DOIUrl":null,"url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"138 ","pages":"Article 109047"},"PeriodicalIF":2.8000,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Protective effect of ginsenoside Rg3 on DBP-induced spermatogenesis injury via the Src/PI3K signaling pathway\",\"authors\":\"Huan Li , Hongyan Wang , Xiaolei Xu, Li Qu, Xiuling Sun, Jing Zhang\",\"doi\":\"10.1016/j.reprotox.2025.109047\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>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.</div></div>\",\"PeriodicalId\":21137,\"journal\":{\"name\":\"Reproductive toxicology\",\"volume\":\"138 \",\"pages\":\"Article 109047\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-09-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Reproductive toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0890623825002187\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"REPRODUCTIVE BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reproductive toxicology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0890623825002187","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"REPRODUCTIVE BIOLOGY","Score":null,"Total":0}
Protective effect of ginsenoside Rg3 on DBP-induced spermatogenesis injury via the Src/PI3K signaling pathway
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.
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.