Celastrol Prevents Oxidative Stress Effects on FSHR, PAPP, and CYP19A1 Gene Expression in Cultured Human Granulosa-Lutein Cells

• Published in: International journal of molecular sciences Vol. 22; no. 7; p. 3596
• Main Authors: Martín-Ramírez, Rita, González-Fernández, Rebeca, Rotoli, Deborah, Hernández, Jairo, Martín-Vasallo, Pablo, Palumbo, Angela, Ávila, Julio
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30.03.2021; MDPI
• Subjects: Adult; Antioxidants; Apoptosis; Aromatase - genetics; Autophagy; celastrol; Cell cycle; Cells, Cultured; Damage prevention; Embryogenesis; Embryos; Endoplasmic reticulum; Female; Fertility; Follicle-stimulating hormone; Folliculogenesis; Gametocytes; Gene expression; Gene Expression - genetics; Gene Expression Regulation - drug effects; Genes; Glucose; Granulosa Cells - drug effects; Granulosa Cells - metabolism; granulosa-lutein cells; Humans; Inductors; Infertility; Kinases; Luteal Cells - drug effects; Luteal Cells - metabolism; Lutein; Oocytes - metabolism; Ovaries; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; Pentacyclic Triterpenes - metabolism; Pentacyclic Triterpenes - pharmacology; Peroxynitrite; Physiology; Pregnancy-Associated Plasma Protein-A - genetics; Primary Cell Culture; Proteins; reactive nitrogen species; reactive oxygen species; Receptors, FSH - genetics; Womens health; celastrol; reactive nitrogen species; oxidative stress; reactive oxygen species; granulosa-lutein cells
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22073596

Regulation of oxidative stress (OS) is important to prevent damage to female reproductive physiology. While normal OS levels may have a regulatory role, high OS levels may negatively affect vital processes such as folliculogenesis or embryogenesis. The aim of this work was to study OS induced by glucose, a reactive oxygen species generator, or peroxynitrite, a reactive nitrogen species generator, in cultured human granulosa-lutein (hGL) cells from oocyte donors, analyzing expression of genes involved in oocyte maturation (FSHR, PAPP, and CYP19A1) and OS damage response (ALDH3A2). We also evaluated the effect of celastrol as an antioxidant. Our results showed that although both glucose and peroxynitrite produce OS increments in hGL cells, only peroxynitrite treatment increases ALDH3A2 and PAPP gene expression levels and decreases FSHR gene expression levels. Celastrol pre-treatment prevents this effect of peroxynitrite. Interestingly, when celastrol alone was added, we observed a reduction of the expression of all genes studied, which was independent of both OS inductors. In conclusion, regulation of OS imbalance by antioxidant substances such as celastrol may prevent negative effects of OS in female fertility. In addition to the antioxidant activity, celastrol may well have an independent role on regulation of gene expression in hGL cells.