Endocrine Abstracts

JOINT1899

The global prevalence of infertility and subfertility has increased significantly, affecting both men and women. Growing evidence suggests that inflammation is a common feature of various pathological conditions and plays a critical role in male reproductive dysfunction by disrupting steroidogenesis and spermatogenesis. Leydig cells (LCs) are essential for sustaining testicular steroidogenesis, a process that relies heavily on mitochondrial function. Mitochondria mediate the initial steps of cholesterol processing and provide the energy required for testosterone synthesis. Although inflammation is known to impair LC steroidogenic function, the precise mechanisms underlying this disruption remain unclear. In this study, we investigated the link between inflammation, steroidogenic dysfunction, and mitochondrial impairment in LCs. Using a Mus musculus Leydig cell line (TM3), we exposed the cells to bacterial lipopolysaccharide (LPS) for 24 hours to induce an inflammatory response. Mitochondrial function was assessed by measuring the oxygen consumption rate (OCR) after mitochondrial modulation. The expression of key steroidogenic genes (STAR and CYP17A1) was analyzed by qPCR, and total testosterone levels in the post-treatment culture medium were quantified using electrochemiluminescence immunoassay. Our findings demonstrate that exposure to an inflammatory stimulus significantly reduces mitochondrial respiration and impairs steroidogenic activity, as evidenced by decreased gene expression and testosterone production. These results provide compelling evidence that local inflammation, independent of systemic inflammatory conditions, disrupts both steroidogenesis and mitochondrial energy production in LCs, highlighting a potential mechanism contributing to male reproductive dysfunction.