Glutathione peroxidase (GPX1) - Selenocysteine metabolism preserves the follicular fluid's (FF) redox homeostasis via IGF-1- NMD cascade in follicular ovarian cysts (FOCs).

Autor: Lava Kumar S; National Institute of Animal Biotechnology, Hyderabad, Telangana 500032, India; Graduate studies, Regional Center for Biotechnology, Faridabad 121 001, India., Kushawaha B; National Institute of Animal Biotechnology, Hyderabad, Telangana 500032, India., Mohanty A; National Institute of Animal Biotechnology, Hyderabad, Telangana 500032, India; Graduate studies, Regional Center for Biotechnology, Faridabad 121 001, India., Kumari A; National Institute of Animal Biotechnology, Hyderabad, Telangana 500032, India; Graduate studies, Regional Center for Biotechnology, Faridabad 121 001, India., Kumar A; National Institute of Animal Biotechnology, Hyderabad, Telangana 500032, India; Graduate studies, Regional Center for Biotechnology, Faridabad 121 001, India., Beniwal R; National Institute of Animal Biotechnology, Hyderabad, Telangana 500032, India; Graduate studies, Regional Center for Biotechnology, Faridabad 121 001, India., Kiran Kumar P; National Institute of Animal Biotechnology, Hyderabad, Telangana 500032, India., Athar M; National Institute of Animal Biotechnology, Hyderabad, Telangana 500032, India; Graduate studies, Regional Center for Biotechnology, Faridabad 121 001, India., Krishna Rao D; Tata Institute of Fundamental Research, Hyderabad, Telangana 500032, India., Rao HBDP; National Institute of Animal Biotechnology, Hyderabad, Telangana 500032, India. Electronic address: prasad@niab.org.in.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2024 Aug; Vol. 1870 (6), pp. 167235. Date of Electronic Publication: 2024 May 12.
DOI: 10.1016/j.bbadis.2024.167235
Abstrakt: Follicular ovarian cysts (FOCs) are characterized by follicles in the ovaries that are >20 mm in diameter and persist for >10 days without the corpus luteum, leading to anovulation, dysregulation of folliculogenesis and subfertility in humans and livestock species. Despite their clinical significance, the precise impact of FOCs on oocyte reserve, maturation, and quality still needs to be explored. While FOCs are observed in both human and livestock populations, they are notably prevalent in livestock species. Consequently, livestock species serve as valuable models for investigating the molecular intricacies of FOCs. Thus, in this study, using goat FOCs, we performed integrated proteomic, metabolomic and functional analyses to demonstrate that oocyte maturation is hampered due to increased reactive oxygen species (ROS) in FOCs follicular fluid (FF) via downregulation of glutathione peroxidase (GPX1), a critical antioxidant seleno enzyme required to negate oxidative stress. Notably, GPX1 reduction was positively correlated with the FF's decline of free selenium and selenocysteine metabolic enzymes, O-phosphoryl-tRNA (Sec) selenium transferase (SEPSECS) and selenocysteine lyase (SCLY) levels. Adding GPX1, selenocysteine, or selenium to the culture media rescued the oocyte maturation abnormalities caused by FOCs FF by down-regulating the ROS. Additionally, we demonstrate that substituting GPX1 regulator, Insulin-like growth factor-I (IGF-1) in the in vitro maturation media improved the oocyte maturation in the cystic FF by down-regulating the ROS activity via suppressing Non-sense-mediated decay (NMD) of GPX1. In contrast, inhibition of IGF-1R and the target of rapamycin complex 1 (mTORC1) hampered the oocyte maturation via NMD up-regulation. These findings imply that the GPX1 regulation via selenocysteine metabolism and the IGF-1-mediated NMD may be critical for the redox homeostasis of FF. We propose that GPX1 enhancers hold promise as therapeutics for enhancing the competence of FOCs oocytes. However, further in vivo studies are necessary to validate these findings observed in vitro.
Competing Interests: Declaration of competing interest The authors have no competing interests related to this work.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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