Indium (III) chloride inhibits testicular Leydig cell proliferation by disrupting centrosome copy numbers

Indium chloride (InCl3), widely used in the electronics and semiconductor industries, has recently been shown to impair testicular development and cause sperm malformations, contributing to male infertility. While testicular Leydig cells are key in testis development and testosterone biosynthesis, the effects of InCl3 on Leydig cell proliferation remain unclear. The present study demonstrated that InCl3 suppresses the proliferation of testicular Leydig cells by disrupting centrosome number regulation. As the centrosome is pivotal in organizing microtubules and forming the mitotic spindle during cell division, InCl3‑induced centrosome amplification leads to abnormal spindle formation and genomic instability. Mechanistically, InCl3 increases reactive oxygen species production, resulting in DNA damage and subsequent activation of DNA‑dependent protein kinase (DNA‑PK), which localizes to the centrosome. Inhibition or knockdown of DNA‑PK attenuated InCl3‑induced centrosome amplification. Additionally, induction of autophagy was observed upon InCl3 exposure and pharmacological inhibition of autophagy using chloroquine suppressed centrosome amplification. Overall, the present findings reveal that InCl3 inhibits Leydig cell proliferation by promoting centrosome amplification and highlights the involvement of DNA‑PK activation and autophagy in this process.