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Granulosa cells from immature follicles exhibit restricted glycolysis and reduced energy production: a dominant problem in polycystic ovary syndrome

  • Reproductive physiology and disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

We hypothesized that immature oocytes are associated with impaired energy production in surrounding granulosa cells (GCs) in polycystic ovary syndrome (PCOS). Thus, this study investigated mitochondrial function, determined expression of glycolytic regulatory enzymes, and measured ATP levels in GCs of PCOS patients.

Methods

GCs were isolated from forty-five PCOS patients and 45 control women. Intracellular concentration of reactive oxygen species (ROS), mitochondrial membrane potential (Δψm), the rate of glycolysis, total antioxidant capacity (TAC), activities of catalase (CAT) and superoxide dismutase (SOD), and ATP level were measured in GCs. The gene expression and protein levels of glycolytic enzymes (hexokinase, muscular phosphofructokinase, platelet derived phosphofructokinase, and muscular pyruvate kinase) were determined. Association of GC energy level with oocyte maturation was further validated by measuring glycolysis rate and ATP level in GCs isolated from mature and immature follicles from new set of fifteen PCOS patients and 15 controls.

Results

PCOS patients showed higher ROS level, decreased TAC, reduced CAT and SOD activities, and lower Δψm together with reduced expression of key glycolytic enzymes. ATP concentration and biochemical pregnancy were lower in PCOS compared with control group. ATP levels were found to be significantly correlated with ROS and Δψm (r = − 0.624 and r = 0.487, respectively). GCs isolated from immature follicles had significantly lower ATP levels and rate of glycolysis compared with the GCs separated from mature follicles in both PCOS patients and control.

Conclusion

Declined energy due to the mitochondrial dysfunction and restrained glycolysis in GCs is associated with the immature oocytes and lower biochemical pregnancy in PCOS.

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Data availability

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors wish to acknowledge Hamadan University of Medical Sciences for the financial support of the study as PhD thesis project (Project NO: 9809056544).

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Authors and Affiliations

  1. Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Sahar Mazloomi, Heidar Tavilani, Jamshid Karimi, Ebrahim Abbasi & Iraj Khodadadi

  2. Fertility Research Centre, Fatemieh Hospital, Hamadan University of Medical Sciences, Hamadan, Iran

    Marzieh Sanoee Farimani & Iraj Amiri

  3. Omid Infertility Centre, Hamadan, Iran

    Marzieh Sanoee Farimani

  4. Department of Anatomy and Embryology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Iraj Amiri

Authors
  1. Sahar Mazloomi
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Contributions

IK and SM contributed to the conceptualization and designing of the study. MSF and IA contributed in provision of materials, collaborated in patient enrolment, and managed sample collection. SM carried out all laboratory works and IK, HT, and JK supervised the experiments. SM and EA collected the data. IK, SM, and EA performed statistical analysis. IK and SM wrote the first draft of the manuscript, and all authors reviewed the manuscript. IK edited the manuscript, and the revised version was approved by all authors. IK supervised the study.

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Correspondence to Iraj Khodadadi.

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Mazloomi, S., Farimani, M.S., Tavilani, H. et al. Granulosa cells from immature follicles exhibit restricted glycolysis and reduced energy production: a dominant problem in polycystic ovary syndrome. J Assist Reprod Genet 40, 343–359 (2023). https://doi.org/10.1007/s10815-022-02676-w

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  • DOI: https://doi.org/10.1007/s10815-022-02676-w

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