N-Acetylcysteine Compared to Metformin, Improves The Expression Profile of Growth Differentiation Factor-9 and Receptor Tyrosine Kinase c-Kit in The Oocytes of Patients with Polycystic Ovarian Syndrome

Ebrahim Cheraghi; Malek Soleimani Mehranjani; Seyed Mohammad Ali Shariatzadeh; Mohammad Hossein Nasr Esfahani; Behrang Alani

doi:10.22074/ijfs.2018.5142

N-Acetylcysteine Compared to Metformin, Improves The Expression Profile of Growth Differentiation Factor-9 and Receptor Tyrosine Kinase c-Kit in The Oocytes of Patients with Polycystic Ovarian Syndrome

Int J Fertil Steril. 2018 Jan;11(4):270-278. doi: 10.22074/ijfs.2018.5142. Epub 2017 Oct 12.

Authors

Ebrahim Cheraghi¹, Malek Soleimani Mehranjani², Seyed Mohammad Ali Shariatzadeh³, Mohammad Hossein Nasr Esfahani⁴, Behrang Alani⁵

Affiliations

¹ Department of Biology, Faculty of Sciences, University of Qom, Qom, Iran.
² Department of Biology, Faculty of Science, Arak University, Arak, Iran. Electronic address: M-soleimani@araku.ac.ir.
³ Department of Biology, Faculty of Science, Arak University, Arak, Iran.
⁴ Department of Reproductive Biotechnology, Reproductive Biomedicine Research Center, Royan Institute, ACECR, Isfahan, Iran.
⁵ Department of Applied Cell Science, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran.

Abstract

Background: Paracrine disruption of growth factors in women with polycystic ovarian syndrome (PCOS) results in production of low quality oocyte, especially following ovulation induction. The aim of this study was to investigate the effects of metformin (MET), N-acetylcysteine (NAC) and their combination on the hormonal levels and expression profile of GDF-9, BMP-15 and c-kit, as hallmarks of oocyte quality, in PCOS patients.

Materials and methods: This prospective randomized, double-blind, placebo controlled trial aims to study the effects of MET, NAC and their combination (MET+NAC) on expression of GDF-9, BMP-15 and c-kit mRNA in oocytes [10 at the germinal vesicle (GV) stage, 10 at the MI stage, and 10 at the MII stage from per group] derived following ovulation induction in PCOS. Treatment was carried out for six weeks, starting on the third day of previous cycle until oocyte aspiration. The expression of GDF9, BMP15 and c-kit were determined by quantitative real time polymerase chain reaction (RT-qPCR) and western blot analysis. Data were analyzed with one-way ANOVA.

Results: The follicular fluid (FF) level of c-kit protein significantly decreased in the NAC group compared to the other groups. Significant correlations were observed between the FF soluble c-kit protein with FF volume, androstenedione and estradiol. The GDF-9 expression in unfertilized mature oocytes were significantly higher in the NAC group compared to the other groups (P<0.001). Similar difference was not observed between the MET, NAC+MET and control groups. The c-kit expression in unfertilized mature oocytes were significantly lower in the NAC group compared to the other groups (P<0.001). Similar difference was not observed between the MET, NAC+MET and control groups (Registration number: IRCT201204159476N1).

Conclusion: We concluded that NAC can improve the quality of oocytes in PCOS.

Keywords: Gene Expression; Metformin; N-acetylcysteine; Oocyte; Polycystic Ovarian Syndrome.