m6A RNA Methylation Modulates Autophagy by Targeting Map1lc3b in Bisphenol A Induced Leydig Cell Dysfunction

Bisphenol A (BPA), a prevalent endocrine disruptor, has been implicated in male reproductive dysfunction, particularly affecting Leydig cells (LCs), which are critical for testosterone production. Here, we explore the impact of BPA on m6A RNA methylation and its regulatory effects on autophagy and LC function. Utilizing both in vivo and in vitro models, we demonstrate that BPA exposure significantly reduces testosterone biosynthesis and upregulates m6A modification in LCs. The m6A 'writer' METTL3 and 'eraser' ALKBH5 were found to play a central role in regulating the m6A levels in Leydig cells upon BPA exposure, and manipulating m6A methylation level mitigates BPA-induced Leydig cell injury. We then performed RNA-seq (also as input) and MeRIP-seq analysis using normal and BPA exposure TM3 Leydig cells.