Indole-3-propionic acid from the gut can mitigate leydig cell dysfunction caused by hyperglycemia by inducing antioxidant pathways

Jozaie, Sadegh; Tabandeh, Mohammad Reza

doi:10.22034/cjvs.2026.546770.1047

Indole-3-propionic acid from the gut can mitigate leydig cell dysfunction caused by hyperglycemia by inducing antioxidant pathways

Document Type : Original Article

Authors

Sadegh Jozaie ¹

Mohammad Reza Tabandeh ²

¹ Department of Basic Sciences, Faculty of Veterinary Medicine, Amol University of Special Modern Technologies, Amol, Iran.

² Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran; Stem Cells and Transgenic Technology Research Center, Shahid Chamran University of Ahvaz, Ahvaz, Iran.

10.22034/cjvs.2026.546770.1047

Abstract

Diabetes mellitus (DM) induces hyperglycemia, increasing reactive oxygen species (ROS) and impairing leydig cell function, thereby contributing to reduced male fertility. Indole-3-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 TM3 leydig cells exposed to high glucose (30 mM). Cells received 20 µM IPA or 1 mM N-acetylcysteine (NAC) as a positive control. Oxidative stress markers (GSH, GSSG, GPx, GR) and pro-inflammatory cytokines (IL-1β, TNF-α) were measured. High-glucose exposure significantly reduced GSH, GPx, and GR levels while increasing GSSG, IL-1β, and TNF-α. IPA treatment increased GSH levels and GR activity and reduced TNF-α compared with the HG group, whereas GPx and IL-1β 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.

Keywords

Hyperglycemia

Indole-3-propionic acid

Leydig cells

Male infertility, Oxidative stress

Subjects