GABARAPL1 is essential for ACR-induced autophagic cell death of mouse Leydig cells.

Acrylamide (ACR), a chemical extensively utilized in industry and food processing sectors, has been recognized for its potentially irreversible adverse effect on male reproductive system; however, the underlying mechanism remains elusive. Our study reveals that ACR markedly triggers oxidative stress-mediated autophagy and upregulates the expression of GABAA-receptor-associated protein like-1 (GABARAPL1). Intriguingly, overexpression of GABARAPL1 significantly induces autophagy, while its knockdown alleviates ACR-induced autophagic responses, underscoring its pivotal function. Furthermore, we demonstrate that transcription factors cAMP response element-binding protein 1 (CREB1) and POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) synergistically enhance Gabarapl1 gene transcription by interacting with its promoter region, contributing to ACR-induced autophagy in mouse Leydig cells. Notably, our findings suggest a reciprocal regulation between PATZ1 and CREB1. This study suggests the critical role of GABARAPL1 in ACR-induced autophagy of mouse Leydig cells, shedding light on the underlying mechanism of ACR-caused male reproductive impairment.