Comparison of the effect of letrozole with N-acetylcysteine on the expression levels of genes involved in glucose metabolism and the expansion of cumulus cells in patients with polycystic ovarian syndrome

Abstract

N-acetylcysteine (NAC) is a recommended adjunct medication used alongside main protocol drugs to induce ovulation in patients diagnosed with polycystic ovary syndrome (PCOS). This supplement contains an excellent source of sulfhydryl groups, which are converted in the body into metabolites that stimulate glutathione production, thereby safeguarding against oocyte damage. A significant number of patients with polycystic ovary syndrome (PCOS) rely on assisted reproductive techniques (ART) to address clnical infertility issues. Notably, the quality of oocytes plays a key role in determining fetal growth and clinical pregnancy in assisted reproductive technalogy. The expansion of oocyte cumulus cells is an essential process for normal oocyte development, ovulation, and fertilization. This biological phenomenon is controlled by specific genes such as VCAN and HAS2, while genes like PFKP and PKM2 play a role in the glucose metabolism of this cells. The levels of gene expression in cumulus cells serve as indicators of oocyte functionality and, subsequently, the potential for embryo development. This research investigates the effects of letrozole and N-acetylcysteine (NAC) on the expression of genes associated with glucose metabolism and the expansion of cumulus cells in patients with polycystic ovary syndrome who were candidates for IVF. Keywords: Letrozole, N-acetylcysteine (NAC), polycystic ovary syndrome (PCOS), cumulus cells. Materials and Methods: This research focused on assessing the effect of letrozole and N-acetylcysteine (NAC) on the expression levels of genes involved in glucose metabolism (PKM2, PFKP) and expansion (HAS2, VCAN) in cumulus cells of patients with polycystic ovary syndrome (PCOS) aged 20-38 years undergoing treatment and in vitro fertilization (IVF) at the infertility center of Al-Zahra Hospital in Tabriz. The gene expression levels were analyzed using RT-PCR and real-time PCR techniques, with statistical analysis conducted using GraphPad Prism 8 software. Findings: The gene expression levels involved in cumulus cell expansion (HAS2) significantly increased in the groups that received NAC compared to the other groups. Moreover, the expression level of the PKM2 gene increased in the letrozole plus NAC compared to the other groups. Furthermore, the expression level of the PFKP gene was elevated in the NAC group compared to both the control and letrozole groups.