Improvement of Late-Onset Hypogonadism Symptoms of Fermented Morinda citrifolia Extract in TM3 Leydig and TM4 Sertoli Cells
2024
Hee-Yeon Kwon | Hyesung Lee | Ji-Soo Choi | Seong Hun Lim | Taehyun Kim | Kyeongseok Bae | Yoon A Jang | Jae-Yeon Lee | Se-Young Choung | Do Sik Min
Background/Objectives: Late-onset hypogonadism (LOH), characterized by declining testosterone levels with age, negatively affects the health of men, causing physical, psychological, and sexual dysfunction. Conventional testosterone replacement therapies have side effects, which has led to interest in natural alternatives. We investigated the effects of a standardized fermented Morinda citrifolia extract (FME) on oxidative stress-induced damage in TM3 Leydig and TM4 Sertoli cells. The cells were treated with H2O2 to simulate oxidative stress, followed by the FME treatment. Methods: Cytotoxicity assays, testosterone measurements, and gene and protein expression analyses were conducted to evaluate the restorative properties of FME. Results: The H2O2 treatment significantly decreased the cell viability, testosterone production, and the expression of proteins involved in testosterone synthesis and spermatogenesis, and the FME treatment improved testosterone production and restored the luteinizing hormone receptor, steroidogenic acute regulatory protein, CYP11A1, 3&beta:-hydroxysteroid dehydrogenase, 17,20 desmolase, and 17&beta:-hydroxysteroid dehydrogenase levels in the TM3 Leydig cells. It also reduced the expression of testosterone-degrading enzymes, aromatase and 5&alpha:-reductase. The FME treatment restored the levels of the androgen receptor and follicle-stimulating hormone receptor in the TM4 Sertoli cells. Conclusions: FME alleviates oxidative stress-induced damage in Leydig and Sertoli cells by promoting testosterone synthesis and spermatogenesis while regulating testosterone metabolism. These findings suggest that FME could be a promising candidate for the management of LOH symptoms.
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