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Follicular Fluid-Derived Exosomal MicroRNA-18b-5p Regulates PTEN-Mediated PI3K/Akt/mTOR Signaling Pathway to Inhibit

Zhi Zhou1, Zhihua Tu1, Juan Zhang2

  • 1Reproductive Medical Center, Hainan Women and Children's Medical Center, No.75 Longkun South Road, Haikou, 570206, Hainan, China.

Molecular Neurobiology
|January 29, 2022
PubMed

Insights

MicroRNA-18b-5p in follicular fluid exosomes may treat polycystic ovary syndrome (PCOS) by downregulating PTEN and activating the PI3K/Akt/mTOR pathway. This research clarifies a key mechanism in PCOS progression and potential therapeutic targets.

Area of Science:

  • Reproductive biology and endocrinology
  • Molecular and cellular biology
  • Exosome and microRNA research

Background:

  • Small RNAs within follicular fluid (FF)-derived exosomes play a role in polycystic ovary syndrome (PCOS) development.
  • MicroRNA (miR)-18b-5p is downregulated, and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is upregulated in PCOS patients.
  • The functional relationship between miR-18b-5p and PTEN in PCOS pathogenesis remains unclear.

Purpose of the Study:

  • To investigate whether miR-18b-5p mediates PCOS progression through PTEN.
  • To explore the therapeutic potential of miR-18b-5p delivered via FF-derived exosomes in PCOS.

Main Methods:

  • Isolation of FF-derived exosomes and co-culture with KGN cells or transfection with PTEN vectors.
  • Establishment of a letrozole-induced PCOS rat model treated with miR-18b-5p-modified exosomes.
  • Measurement of cell proliferation, apoptosis, serum hormone levels (FSH, LH, testosterone, E2), and key pathway gene expression (miR-18b-5p, PTEN, PI3K/Akt/mTOR).

Main Results:

  • In PCOS patients, miR-18b-5p was downregulated and PTEN highly expressed in FF and GCs.
  • Exosomes delivering miR-18b-5p reduced PTEN expression, increased KGN cell proliferation, decreased apoptosis, and improved hormonal balance in PCOS rats.
  • miR-18b-5p directly targets PTEN, leading to the activation of the PI3K/Akt/mTOR signaling pathway.

Conclusions:

  • miR-18b-5p delivered by FF-derived exosomes ameliorates PCOS by downregulating PTEN and activating the PI3K/Akt/mTOR pathway.
  • Circulating miR-18b-5p levels are implicated in the progression of PCOS complications.
  • miR-18b-5p represents a potential therapeutic target for PCOS.
Keywords:
Follicular fluid-derived exosomesMicroRNA-18b-5pPI3K/Akt/mTOR pathwayPTENPolycystic ovary syndrome

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