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

  • Reproductive Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To investigate whether fatty acid changes in granulosa cells (GCs) underly the pathogenic mechanisms of diminished ovarian reserve (DOR).

Methods

GCs were obtained from patients with DOR (n = 70) and normal ovarian reserve (NOR, n = 70). Analysis of fatty acids changes in GCs was then analyzed.

Results

Patients with DOR had significantly lower levels of antral follicle count and anti-Mullerian hormone and higher levels of follicle-stimulating hormone compared with NOR patients (P < 0.001). The good-quality embryo rate was notably decreased in DOR patients (51.99 vs 39.52%, P < 0.05). A total of 15 significantly decreased fatty acids in GCs from patients with DOR. The ATP levels were markedly lower in DOR patients than in NOR patients (39.07 ± 12.89 vs 23.21 ± 13.69%, P < 0.05). Mitochondrial membrane potential decreased in DOR patients (P < 0.01). In GCs from DOR patients, the β-oxidation genes (HADHA and ACSL) and DNA repair genes (PRKDC and RAD50) were significantly downregulated (P < 0.05). The γH2AX foci/nucleus ratio in DOR patients markedly increased relative to that of NOR patients (0.31 ± 0.03 vs 0.87 ± 0.07, P < 0.001). Meanwhile, the apoptosis rate of GCs was significantly higher in DOR patients (6.43 ± 2.11 vs 48.06 ± 6.72%, P < 0.01).

Conclusion

GC apoptosis resulting from the decrease of fatty acids, and associated with reduced ATP production and DNA damage, may contribute to the pathogenic mechanisms responsible for DOR.

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Acknowledgements

This research was supported by the National Natural Science Foundation of China(No.81960278), the Outstanding Youth Funds of Science and Technology Department of Gansu Province (No.20JR5RA371)(No.20JR10RA701), and Fundamental Research Funds for the Central Universities (No.lzujbky-2021-kd38)

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Authors and Affiliations

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

    Zhongying Zhao, Qigang Fan, Qinying Zhu, Ruifen He & Yi Li

  2. Department of Obstetrics and Gynecology, Key Laboratory for Gynecologic Oncology Gansu Province, The First Hospital of Lanzhou University, The First Clinical Medical College of Lanzhou University, Lanzhou, China

    Chang Liu, Jing Wang & Xiaolei Liang

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  1. Zhongying Zhao
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Correspondence to Xiaolei Liang.

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Zhao, Z., Fan, Q., Zhu, Q. et al. Decreased fatty acids induced granulosa cell apoptosis in patients with diminished ovarian reserve. J Assist Reprod Genet 39, 1105–1114 (2022). https://doi.org/10.1007/s10815-022-02462-8

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