A primary insight into gut microbiome, MicroRNA and stemness, in a PCOS rat model

Area of Science:

• Endocrinology
• Microbiology
• Stem Cell Biology

Background:

• Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder linked to reproductive and metabolic issues, including gut dysbiosis.
• The interplay between gut microbiome alterations and ovarian dysfunction in PCOS remains incompletely understood.

Purpose of the Study:

• To investigate changes in ovarian stemness, gut microbiome composition, and microRNA profiles in a dihydrotestosterone (DHT)-induced rat model of PCOS.
• To explore the potential connection between gut microbiome dysbiosis and enhanced ovarian stemness in PCOS.

Main Methods:

• PCOS was induced in female rats using DHT administration.
• Ovarian surface epithelium (OSE) stemness was assessed via stem cell marker expression.
• Gut microbiome composition was analyzed using 16S rRNA gene Long-Read sequencing.
• MicroRNA expression in granulosa cells and plasma was quantified using qPCR.

Main Results:

• DHT-induced PCOS rats exhibited altered stemness markers in OSE and significant gut microbiome dysbiosis, notably changes in Akkermansia muciniphila abundance.
• Elevated plasma levels of miR-574 and miR-378 were detected.
• Increased expression of miR-21 and miR-574 was observed in ovarian granulosa cells, alongside enhanced stem cell marker expression in OSE.

Conclusions:

• A potential link exists between gut microbiome dysbiosis and increased ovarian stemness in PCOS.
• The gut microbiome may contribute to ovarian dysfunction in PCOS by modulating ovarian stem cell activity.
• These findings offer novel insights into potential therapeutic targets for restoring ovarian function in PCOS patients.