Involvement of ARG2‐Mediated Autophagy in Di‐2‐ethylhexyl Phthalate‐Induced Testicular Injury

ABSTRACT

Di‐2‐ethylhexyl phthalate (DEHP) is a common industrial chemical with endocrine‐disrupting properties, which is capable of causing developmental abnormalities in the male reproductive system, while the effect of DEHP on testicular cell autophagy and its specific molecular mechanism has not been fully clarified. In the present study, Leydig cells were adopted as the research cell model, and multiple experimental techniques including CCK‐8 assay, ELISA, flow cytometry, immunofluorescence staining and Western blot were applied to explore the effects of DEHP on Leydig cell autophagy and its correlation with Arg2. The experimental results showed that DEHP exposure could inhibit the proliferation and secretory function of Leydig cells, decrease testosterone levels and trigger cell apoptosis. Meanwhile, DEHP treatment significantly elevated the autophagy level of Leydig cells, accompanied by the upregulated expression of autophagy‐related genes Beclin1 and LC3B. Moreover, DEHP exposure induced the upregulation of Arg2 expression in Leydig cells, and the knockdown of Arg2 could partially reverse the increased autophagy level and alleviate Leydig cell damage caused by DEHP. Further mechanistic experiments verified that Arg2 might regulate DEHP‐induced autophagy via the mTOR signaling pathway. This study confirms that Arg2‐mediated autophagy participates in the process of DEHP‐induced Leydig cell injury, which provides a novel theoretical basis and research perspective for further exploring the toxic mechanism of DEHP on the male reproductive system.