Ginsenoside Rg1 alleviates chronic testicular damage caused by cranial irradiation through the SCF/PI3K/Akt/mTOR pathway in mice
Objective: To investigate whether Ginsenoside Rg1 can mitigate the adverse effects of cranial irradiation on distal reproductive function in mice and to explore the underlying mechanisms. Methods: Forty male C57BL/6J mice were randomly divided to four groups [Control, irradiation (IR), IR + Rg1, R...
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Main Authors: | , , , , , , |
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Format: | Article |
Language: | English |
Published: |
Elsevier
2025-02-01
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Series: | Radiation Medicine and Protection |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2666555724001199 |
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Summary: | Objective: To investigate whether Ginsenoside Rg1 can mitigate the adverse effects of cranial irradiation on distal reproductive function in mice and to explore the underlying mechanisms. Methods: Forty male C57BL/6J mice were randomly divided to four groups [Control, irradiation (IR), IR + Rg1, Rg1), IR + Rg1 and Rg1 group treated with intraperitoneal injections of Ginsenoside Rg1 for 30 d, followed by single-dose irradiation of 5 Gy X-ray irradiation (2 Gy/min) for the IR and IR + Rg1 group. After three months, testicles, whole brain, and serum samples were collected for analysis. Results: Histological staining, transmission electron microscopy, sperm analysis, and immunofluorescence demonstrated that Ginsenoside Rg1 ameliorated structural and functional damage to the testicles, enhanced sperm count (IR: 20.70 ± 1.62 vs. IR + Rg1: 33.93 ± 2.20, t = −13.23, P < 0.05), and reduced sperm malformation rates (IR: 46.33 ± 2.18 vs. IR + Rg1: 39.00 ± 1.67, t = 7.33, P < 0.05). Further Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and Enzyme linked immunosorbent assay (ELISA) assays demonstrated that Rg1 inhibited testicular apoptosis (IR: 3.21 ± 0.28 vs. IR + Rg1: 1.81 ± 0.18, t = 1.40, P < 0.05) and modulated serum testosterone (IR: 4.47 ± 0.23 vs. IR + Rg1: 6.65 ± 0.09, t = −2.18, P < 0.05), GnRH (IR: 24.37 ± 0.92 vs. IR + Rg1: 32.98 ± 1.33, t = −8.61, P < 0.05), and FSH levels (IR: 1.41 ± 0.11 vs. IR + Rg1: 2.69 ± 0.21, t = −1.28, P < 0.05). Additionally, quantitative PCR and Western blot showed that Rg1 downregulated SCF, p-PI3K, p-Akt, and mTOR protein expressions in irradiated mice. Conclusions: Ginsenoside Rg1 potentially alleviate chronic testicular structural and functional damage by inhibiting germ cell apoptosis through the modulation of the HPG axis and the PI3K/Akt/mTOR pathway, suggesting that it is a potential therapeutic agent for reproductive disorders induced by cranial irradiation. |
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ISSN: | 2666-5557 |