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703 Changes in the energy metabolism of the cumulus granulosa cells in patients with premature ovarian insufficiency
  1. Weronika Marynowicz1,2,
  2. Paulina Glód1,2,
  3. Justyna Gogola-Mruk2,
  4. Dawid Maduzia3 and
  5. Anna Ptak2
  1. 1Jagiellonian University, Doctoral School of Exact and Natural Sciences, Cracow, Poland
  2. 2Jagiellonian University, Faculty of Biology, Institute of Zoology and Biomedical Research, Laboratory of Physiology and Toxicology of Reproduction, Cracow, Poland
  3. 3Infertility Treatment Centre PARENS, Cracow, Poland


Introduction/Background The incidence of premature ovarian insufficiency (POI) is estimated to affect 1 in 100 women under the age of 40 and is a leading cause of infertility in women. Due to the increasing trend of late childbearing in developed countries, the incidence of POI has increased and became an important clinical problem requiring infertility treatment. The aim of this research was to determine whether POI is associated with disruption of the metabolic phenotype of human granulosa cells (GCs).

Methodology Study included 25 women undergoing IVF (the Ethical Committee of the Jagiellonian University, 1072.6120.30.2023). POI was defined according to the European Society of Human Reproduction and Embryology criteria (age<40, AMH<1.1 ng/ml). Human GCs isolated from follicular fluid and cumulus from POI and control women were analysed ex vivo. The energetic phenotype and ATP production from glycolysis and mitochondria simultaneously was performed using Seahorse XF analyser (Agilent). Expression of HK2 and IDH2 genes was determined by RT-qPCR.

Results We showed that mural GCs from healthy patients have a typical metabolic phenotype with dominant mitochondrial ATP production, whereas cumulus GCs produce ATP from both mitochondrial and glycolytic processes at the same level. These findings are confirmed by the expression of the HK2 and IDH2 genes. We observed that in cumulus GCs from POI patients, ATP is mainly produced by aerobic glycolysis and the role of OXPHOS-related ATP production is reduced. Moreover, we found that these metabolic changes in cumulus GCs are associated with change in HK2 and IDH2 expression levels.

Conclusion These results suggest that cumulus GCs from POI patients have alternative bioenergetic properties compared to control patients. Cumulus cells of POI women are in an energetic imbalance, which may affect oocyte quality and cause fertility problems. This research provides an important insight into the cellular bioenergetics of human GCs.

Disclosures This study was funded by the National Science Centre (NCN) Poland (grant no. 2022/45/B/NZ7/00254).

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