Abstract
IN BRIEF: Sulfiredoxin (Srxn1) is essential for corpus luteum formation during ovulation. Inhibition of Srxn1 with J14 suppressed LH-stimulated progesterone production, key gene expressions (Cyp11a1, Star), and markers of luteinization. This highlights Srxn1's role in promoting LH-induced luteinization through the ERK, C/EBPβ, and Cyp11a1 pathways. ABSTRACT: Sulfiredoxin (Srxn1), an antioxidant enzyme, is expressed during ovulation. This study aimed to investigate the physiological function of Srxn1 in corpus luteum formation during the ovulatory process in rats. Treatment of cultured preovulatory follicles with the Srxn1 inhibitor, J14, suppressed LH-stimulated progesterone production, but not estradiol production, in a dose-dependent manner. Likewise, LH-stimulated gene expression of Cyp11a1 and Star, but not Cyp19a1, was suppressed by J14. Regulation of Cyp11a1 and STAR expression by Srxn1 was confirmed using si-Srxn1 in KGN cells, a human granulosa cell line. Furthermore, treatment of preovulatory granulosa cells with J14 dose-dependently suppressed LH-stimulated mRNA and protein levels of C/EBPβ and ERK1/2. Finally, hypertrophy, lipid droplets, progesterone production, and p27Kip1 expression stimulated by LH were significantly lowered by J14 in in vitro luteinization of granulosa cells. Taken together, the present data indicate that Srxn1 plays a significant role in the formation of the corpus luteum during ovulation by stimulating the pathways of ERK, C/EBPβ, and Cyp11a1.