Bacterial LPS-induced inflammation reduces aquaglyceroporin-mediated glycerol permeability in TM3 mouse leydig cells and is associated with impaired mitochondrial respiration.

Inflammation accompanies a wide range of pathological conditions and negatively impacts the male reproductive function by interfering with steroidogenesis and spermatogenesis. Steroidogenesis is sustained by Leydig cells (LCs), but it can be impaired by local or systemic inflammatory events known to alter the expression and function of aquaporins (AQPs). In addition, glycerol acts as an osmolyte and a metabolic substrate that supports cellular homeostasis and contributes to the proper function of testicular cells. To investigate the effects of inflammation on aquaglyceroporins (AQGPs) and glycerol transport, Mus musculus LCs (TM3) were exposed to bacterial lipopolysaccharide (LPS) for 24 h to induce an inflammatory-like state; this promoted a decrease in glycerol permeability, assessed by stopped-flow light scattering, and increased expression of the Aqp9 transcript. Furthermore, inflammatory stimulation was associated with impaired mitochondrial respiration activity, reflected by decreased oxygen consumption rates linked to ATP production (OCR), as well as reduced expression of the steroidogenic genes Star and Cyp17a1 and lower testosterone production. Collectively, these findings demonstrate that inflammation is associated with alterations in Aqp9 expression, glycerol permeability, mitochondrial respiratory parameters, and steroidogenic activity in TM3 mLCs. Though the mechanisms linking glycerol homeostasis, cellular energy metabolism, and hormone production under inflammatory conditions warrant further investigation, this work provides first-time evidence of a correlation between inflammation-induced metabolic and hormonal disruptions and impairment of glycerol transport in TM3 LCs.