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Adipose-Derived Mesenchymal Stem Cells and Their Exosomes Ameliorate Sperm-related Abnormalities, Hormonal Imbalance, and Disrupted Testicular Autophagy in A Diet-Induced Murine Model for Non-Alcoholic Fatty Liver Disease
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DOI：10.1007/s43032-026-02158-9.png)
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Abstract
En 中文
Non-alcoholic fatty liver disease (NAFLD), a common metabolic disorder, is increasingly linked to impaired male reproductive health. This study investigates the therapeutic potential of adipose-derived mesenchymal stem cells (AD-MSCs) and their exosomes (AD-MSCs-Exo) in ameliorating NAFLD-induced testicular dysfunction in a murine model. Male C57BL/6 mice were divided into four groups: [n = 8 per group: control, high-fat diet (HFD), HFD + AD-MSCs, and HFD + AD-MSCs-Exo]. Sperm parameters according to the WHO Laboratory Manual, hormonal profiles via ELISA, and expression of genes involved in autophagy and spermatogenesis were assessed using qRT-PCR. HFD-induced NAFLD significantly reduced sperm count (P = 0.036), motility (P < 0.0001), viability (P = 0.023), and normal morphology (P = 0.015) while increasing DNA fragmentation (P = 0.004). Moreover, in the HFD group, LH and total testosterone levels decreased significantly (P = 0.0002 and P < 0.0001), whereas estradiol levels increased significantly (P = 0.0001) compared with controls. Expression of STAR was significantly downregulated (P = 0.0001); conversely, the relative fold changes of BECN1 (P = 0.0003), MAP-LC3b-a (P = 0.0002), and SQSTM-1/p62 (P = 0.005) were significantly enhanced in the HFD group compared to the controls. Treatment with AD-MSCs or AD-MSCs-Exo improved sperm quantity and quality and balanced hormonal levels. AD-MSCs showed slightly greater modulation of key autophagy genes (BECN1, MAP-LC3b-a, and SQSTM1/p62), whereas exosomes were more effective in hormonal restoration (especially testosterone) and in enhancing genes related to steroidogenesis (especially INHBB). AD-MSCs and their exosomes improve sperm-related abnormalities, hormonal imbalance, and testicular autophagy dysregulation in the NAFLD model. These findings support their potential as therapeutic agents for NAFLD-induced male infertility, highlighting translational relevance while noting the need for further clinical validation.
Keywords:
Non-alcoholic fatty liver disease
Mesenchymal stem cells
Exosomes
Spermatogenesis
Autophagy
Testosterone
Mice
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