ENERJİ STRESİNDE GRANÜLOZA HÜCRELERİNİN ACE2 İFADELENMESİNİN SIRT1 İLE İLİŞKİSİNİN DEĞERLENDİRİLMESİ

Abstract

Nikshiqi Erblina, Evaluation of the Relationship Between ACE2 Expression and SIRT1 in Granulosa Cells Under Energy Stress, Hacettepe University Faculty of Medicine, Department of Histology and Embryology Residency Thesis, Ankara 2024. Cellular energy stress arises from an increased demand for energy and a decreased energy supply, thereby affecting cellular metabolism. Adenosine monophosphate-activated protein kinase (AMPK), a key regulator of cellular energy homeostasis, is activated under limited energy reserves to regulate various physiological processes. In response to increased AMPK, SIRT1 modulates cellular processes such as energy metabolism and stress response. ACE2, expressed in human granulosa cells, plays a significant role in steroidogenesis, folliculogenesis, follicular atresia, granulosa-lutein cell apoptosis, oocyte maturation, and ovulation. ACE2 levels are linked to cellular energy stress. Cells produce 88% of their energy source, ATP, from mitochondrial oxidation in order to survive. Granulosa cells are crucially important cells that play a role in follicular development in the ovarian cycle. The metabolic changes these cells undergo is important for fertility. Based on what is known, an observational descriptive study was planned to investigate the relationship between ACE2 expression and SIRT1 in granulosa cells through AMPK activation induced by AICAR treatment. In the HGL5 human granulosa cell line, it was found that mitochondrial membrane potential decreased after cellular energy stress, and this damage was further exacerbated after SIRT1 inhibition. After establishing an energy stress model, our study results showed that SIRT1 statistically increased in the HGL5 granulosa cells, primary cultured healthy and PCOS granulosa cells group via indirect immunofluorescent staining method. In the Diminished Ovarian Reserve (DOR) group, our study results showed that after cellular energy stress, SIRT1 decreased compared to the control group. After SIRT1 inhibition, ACE2 expression increased in all groups except the DOR group. For the first time, our study demonstrated a potential relationship between SIRT1 and ACE2 in granulosa cells via the AMPK pathway.