Indole-۳-propionic acid from the gut can mitigate leydig cell dysfunction caused by hyperglycemia by inducing antioxidant pathways

Diabetes mellitus (DM) induces hyperglycemia, increasing reactive oxygen species (ROS) and impairing leydig cell function, thereby contributing to reduced male fertility. Indole-۳-propionic acid (IPA), a gut microbiota–derived tryptophan metabolite with antioxidant and anti-inflammatory properties, has not been sufficiently investigated in hyperglycemia-induced reproductive damage. This study evaluated the protective effects of IPA on TM۳ leydig cells exposed to high glucose (۳۰ mM). Cells received ۲۰ µM IPA or ۱ mM N-acetylcysteine (NAC) as a positive control. Oxidative stress markers (GSH, GSSG, GPx, GR) and pro-inflammatory cytokines (IL-۱β, TNF-α) were measured. High-glucose exposure significantly reduced GSH, GPx, and GR levels while increasing GSSG, IL-۱β, and TNF-α. IPA treatment increased GSH levels and GR activity and reduced TNF-α compared with the HG group, whereas GPx and IL-۱β showed no significant changes. Overall, these findings indicated that IPA mitigates hyperglycemia-induced oxidative stress and inflammation mainly through enhancing the glutathione redox cycle and modulating inflammatory mediators, highlighting its potential to preserve leydig cell function.

کلیدواژه ها:

Hyperglycemia ، Indole-۳-propionic acid ، Leydig cells ، Male infertility ، Oxidative stress