Icariin Improves D-Gal-Induced Sertoli Cell Dysfunction by Activating Autophagy-Lysosomal-Mitochondrial Pathway

Area of Science:

• Reproductive Biology
• Cellular Biology
• Molecular Medicine

Background:

• Epimedium brevicornu Maxim (Yinyanghuo) is traditionally used for reproductive disorders.
• Icariin (ICA), its active component, shows potential in alleviating testicular dysfunction and Sertoli cell injury.
• The role of ICA in regulating Sertoli cell autophagy and function requires further investigation.

Purpose of the Study:

• To investigate the protective effects of Icariin (ICA) on D-Galactose (D-gal)-induced Sertoli cell dysfunction.
• To evaluate ICA's impact on mitochondrial biogenesis, lysosome biogenesis, and autophagic activity in Sertoli cells.
• To elucidate the mechanisms by which ICA improves Sertoli cell function.

Main Methods:

• TM4 Sertoli cells were pretreated with ICA and exposed to D-galactose.
• Cell viability, oxidative stress, and apoptosis were assessed.
• Mitochondrial and lysosomal biogenesis were analyzed using specific trackers and protein/mRNA expression levels (TFEB, LAMP2).
• Autophagy-related proteins (PINK1, Parkin, ATG5, ULK1, LC3-II) and functional markers (GDNF, Claudin5) were quantified.

Main Results:

• ICA treatment significantly enhanced Sertoli cell viability and protected against D-gal-induced oxidative stress and apoptosis.
• ICA promoted lysosomal biogenesis by increasing TFEB and LAMP2 expression.
• ICA activated autophagy, evidenced by increased expression of PINK1, Parkin, ATG5, ULK1, and LC3-II, leading to improved Sertoli cell function and increased GDNF and Claudin5 levels.

Conclusions:

• Icariin (ICA) alleviates D-galactose-induced Sertoli cell injury by mitigating oxidative stress.
• ICA enhances Sertoli cell function through the activation of autophagy and promotion of lysosome and mitochondrial biogenesis.
• These findings highlight ICA's therapeutic potential for reproductive disorders linked to Sertoli cell dysfunction.