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Decreased fatty acids induced granulosa cell apoptosis in patients with diminished ovarian reserve

Zhongying Zhao1, Qigang Fan1, Qinying Zhu1

  • 1The First Clinical Medical College of Lanzhou University, Lanzhou, China.

Journal of Assisted Reproduction and Genetics
|March 29, 2022
PubMed
Abstract

Insights

Decreased fatty acids in granulosa cells (GCs) are linked to diminished ovarian reserve (DOR). This reduction in fatty acids contributes to GC apoptosis, reduced ATP production, and DNA damage, potentially driving DOR pathogenesis.

Area of Science:

  • Reproductive biology
  • Cellular and molecular mechanisms of fertility
  • Ovarian reserve research

Background:

  • Diminished ovarian reserve (DOR) is a significant cause of infertility in women.
  • The underlying cellular and molecular mechanisms of DOR are not fully understood.
  • Granulosa cells (GCs) play a crucial role in ovarian function and follicle development.

Purpose of the Study:

  • To investigate the role of fatty acid alterations in granulosa cells (GCs) as a potential mechanism in the pathogenesis of diminished ovarian reserve (DOR).
  • To explore the relationship between fatty acid profiles in GCs and key indicators of ovarian function.

Main Methods:

  • Granulosa cells (GCs) were collected from patients diagnosed with DOR (n=70) and those with normal ovarian reserve (NOR, n=70).
  • Comprehensive analysis of fatty acid composition within GCs was performed.
  • Key indicators of ovarian reserve, including antral follicle count, anti-Mullerian hormone (AMH), and follicle-stimulating hormone (FSH) levels, were assessed.

Main Results:

  • DOR patients exhibited significantly lower antral follicle count and AMH levels, alongside higher FSH levels, compared to NOR patients.
  • The rate of good-quality embryo formation was significantly reduced in the DOR group.
  • GCs from DOR patients showed a significant decrease in 15 fatty acids, lower ATP levels, and reduced mitochondrial membrane potential.
  • Downregulation of beta-oxidation (HADHA, ACSL) and DNA repair genes (PRKDC, RAD50) was observed in DOR GCs.
  • Increased DNA damage (γH2AX foci) and a higher rate of GC apoptosis were evident in DOR patients.

Conclusions:

  • Decreased fatty acid levels in granulosa cells may contribute to diminished ovarian reserve (DOR) by promoting GC apoptosis.
  • The observed reduction in fatty acids is associated with impaired ATP production and increased DNA damage in GCs.
  • These cellular dysfunctions, driven by fatty acid alterations, represent a potential pathogenic pathway for DOR.
Keywords:
ATP productionDNA damageDiminished ovarian reserveFatty acidsGranulosa cell apoptosis

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