MicroRNA-338-3p helps regulate ovarian function by affecting granulosa cell function and early follicular development

Area of Science:

• Reproductive Biology
• Molecular Endocrinology
• Ovarian Physiology

Background:

• Mammalian ovarian follicular development is a complex process regulated by intricate interactions within the follicular microenvironment, granulosa cells (GCs), and oocytes.
• Aberrant follicular development can lead to infertility, highlighting the critical need to understand its underlying pathogenesis.
• Investigating the molecular mechanisms governing follicular development is essential for diagnosing and treating female infertility.

Purpose of the Study:

• To investigate the role of microRNA-338-3p (miR-338-3p) in mammalian follicular development and ovarian function.
• To elucidate the pathogenic mechanisms of abnormal follicular development associated with miR-338-3p.
• To explore the potential of miR-338-3p as a diagnostic or therapeutic target for infertility.

Main Methods:

• RNA sequencing of ovarian cortical tissues from patients with normal ovarian function and ovarian insufficiency.
• In situ hybridization to determine the expression patterns of miR-338-3p in GCs and oocytes.
• In vitro culture models using GCs and neonatal mouse ovaries to assess the biological effects of miR-338-3p.
• In vivo experiments involving the injection of adeno-associated virus vectors for miR-338-3p overexpression in mouse ovarian bursae.

Main Results:

• miR-338-3p was significantly upregulated in ovarian cortical tissues and GCs of patients with ovarian insufficiency and diminished ovarian reserve.
• Overexpression of miR-338-3p in vitro suppressed GC proliferation and estradiol production, and impaired early follicular development in neonatal mouse ovaries.
• In vivo administration of miR-338-3p led to decreased oocyte mitochondrial membrane potential and disrupted estrous cycles in mice.
• miR-338-3p appears to regulate GC proliferation and early follicular development via transforming growth factor β signaling.

Conclusions:

• miR-338-3p plays a crucial role in regulating early follicular development and normal ovarian function by modulating GC proliferation and estradiol production.
• The findings elucidate the regulatory mechanism of miR-338-3p in follicular development, offering insights into the pathogenesis of ovarian dysfunction.
• This study provides a foundation for novel diagnostic and therapeutic strategies targeting miR-338-3p for infertility associated with abnormal follicular development.