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SCF/C-kit drives spermatogenesis disorder induced by abscopal effects of cranial irradiation in mice.
- Source :
-
Ecotoxicology and environmental safety [Ecotoxicol Environ Saf] 2024 Jul 01; Vol. 279, pp. 116504. Date of Electronic Publication: 2024 May 24. - Publication Year :
- 2024
-
Abstract
- Cranial radiotherapy is a major treatment for leukemia and brain tumors. Our previous study found abscopal effects of cranial irradiation could cause spermatogenesis disorder in mice. However, the exact mechanisms are not yet fully understood. In the study, adult male C57BL/6 mice were administrated with 20 Gy X-ray cranial irradiation (5 Gy per day for 4 days consecutively) and sacrificed at 1, 2 and 4 weeks. Tandem Mass Tag (TMT) quantitative proteomics of testis was combined with bioinformatics analysis to identify key molecules and signal pathways related to spermatogenesis at 4 weeks after cranial irradiation. GO analysis showed that spermatogenesis was closely related to oxidative stress and inflammation. Severe oxidative stress occurred in testis, serum and brain, while serious inflammation also occurred in testis and serum. Additionally, the sex hormones related to hypothalamic-pituitary-gonadal (HPG) axis were disrupted. PI3K/Akt pathway was activated in testis, which upstream molecule SCF/C-Kit was significantly elevated. Furthermore, the proliferation and differentiation ability of spermatogonial stem cells (SSCs) were altered. These findings suggest that cranial irradiation can cause spermatogenesis disorder through brain-blood-testicular cascade oxidative stress, inflammation and the secretory dysfunction of HPG axis, and SCF/C-kit drive this process through activating PI3K/Akt pathway.<br />Competing Interests: Declaration of Competing Interest All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Male
Mice
Testis radiation effects
Testis pathology
Signal Transduction radiation effects
Stem Cell Factor metabolism
Inflammation
Spermatogenesis radiation effects
Mice, Inbred C57BL
Proto-Oncogene Proteins c-kit metabolism
Oxidative Stress radiation effects
Cranial Irradiation adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2414
- Volume :
- 279
- Database :
- MEDLINE
- Journal :
- Ecotoxicology and environmental safety
- Publication Type :
- Academic Journal
- Accession number :
- 38795418
- Full Text :
- https://doi.org/10.1016/j.ecoenv.2024.116504