Granulosa cell insight: unraveling the potential of menstrual blood-derived stem cells and their exosomes on mitochondrial mechanisms in polycystic ovary syndrome (PCOS)

颗粒细胞洞察:揭示月经血来源的干细胞及其外泌体对多囊卵巢综合征(PCOS)中线粒体机制的潜力

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作者:Mahna Mansoori, Somayeh Solhjoo, Maria Grazia Palmerini, Seyed Noureddin Nematollahi-Mahani, Massood Ezzatabadipour

Background

Polycystic ovary syndrome (PCOS) presents a significant challenge in women's reproductive health, characterized by disrupted folliculogenesis and ovulatory dysfunction. Central to PCOS pathogenesis are granulosa cells, whose dysfunction contributes to aberrant steroid hormone production and oxidative stress. Mitochondrial dysfunction emerges as a key player, influencing cellular energetics, oxidative stress, and steroidogenesis. This study investigates the therapeutic potential of menstrual blood-derived stem cells (MenSCs) and their exosomes in mitigating mitochondrial dysfunction and oxidative stress in PCOS granulosa cells.

Conclusions

This study offers insights into granulosa cells mitochondria's role in PCOS pathogenesis and proposes MenSCs and exosomes as a potential strategy for mitigating mitochondrial dysfunction and oxidative stress in PCOS. Further research is needed to understand underlying mechanisms and validate clinical efficacy, presenting promising avenues for addressing PCOS complexity.

Methods

Using a rat model of PCOS induced by letrozole, granulosa cells were harvested and cultured. MenSCs and their exosomes were employed to assess their effects on mitochondrial biogenesis, oxidative stress, and estrogen production in PCOS granulosa cells.

Results

Results showed diminished mitochondrial biogenesis and increased oxidative stress in PCOS granulosa cells, alongside reduced estrogen production. Treatment with MenSCs and their exosomes demonstrated significant improvements in mitochondrial biogenesis, oxidative stress levels, and estrogen production in PCOS granulosa cells. Further analysis showed MenSCs' superior efficacy over exosomes, attributed to their sustained secretion of bioactive factors. Mechanistically, MenSCs and exosomes activated pathways related to mitochondrial biogenesis and antioxidative defense, highlighting their therapeutic potential for PCOS. Conclusions: This study offers insights into granulosa cells mitochondria's role in PCOS pathogenesis and proposes MenSCs and exosomes as a potential strategy for mitigating mitochondrial dysfunction and oxidative stress in PCOS. Further research is needed to understand underlying mechanisms and validate clinical efficacy, presenting promising avenues for addressing PCOS complexity.

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