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Pyridaben induces mitochondrial dysfunction and leads to latent male reproductive abnormalities

Authors
Ham, JiyeonYou, SeungkwonLim, WhasunSong, Gwonhwa
Issue Date
1월-2021
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Keywords
Pyridaben; Pesticides; Testis; Mitochondrial dysfunction; Male infertility
Citation
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY, v.171
Indexed
SCIE
SCOPUS
Journal Title
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
Volume
171
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/50263
DOI
10.1016/j.pestbp.2020.104731
ISSN
0048-3575
Abstract
As an organochloride pesticide, pyridaben (PDB) has been used on various plants, including fruiting plants and other crops. Because of emerging concerns regarding exposure to pesticides, the deleterious effects of PDB, including neuronal disease and reproductive abnormalities, have been determined. However, the intracellular mechanisms that contribute to the effects of PDB on the male reproductive system are still unknown. Therefore, we investigated the effects of PDB on the male reproductive organ, focusing on the testes using mouse testicular cells. We demonstrated that PDB suppressed cellular proliferation of mouse Leydig (TM3) and Sertoli (TM4) cells. Additionally, PDB disturbed calcium homeostasis via mitochondrial dysfunction and activation of endoplasmic reticulum stress. Furthermore, PDB inhibited transcriptional gene expression regarding the cell cycle, as well as steroidogenesis and spermatogenesis, which are the primary functions of TM3 and TM4 cells. Moreover, we verified via western blot analysis that PDB dysregulated the intracellular cell signaling pathways in mitochondrial-associated membranes and the Mapk/Pi3k pathway. Lastly, we confirmed that PDB efficiently suppressed the spheroid formation of TM3 and TM4 cells mimicking an in vivo environment. Collectively, the current results indicate that PDB induces testicular toxicity and male reproductive abnormalities by inducing mitochondrial dysfunction, endoplasmic reticulum stress and calcium imbalance.
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