Oxr1a prevents the premature ovarian failure by regulating oxidative stress and mitochondrial function in zebrafish.
Free Radic Biol Med
; 203: 102-113, 2023 07.
Article
in En
| MEDLINE
| ID: mdl-37031846
ABSTRACT
Premature ovarian failure (POF) is characterized as the ovarian dysfunction and defective oocyte development. In POF patients, ROS level is reported to be significantly higher than normal individuals. However, the involvement of oxidative stress in POF and the regulatory mechanisms underlying the antioxidative process in oocyte development remain largely unknown. Here, we discover that oxidation resistance 1a (Oxr1a), the ortholog of mammalian Oxr1, protects the oocytes of female zebrafish against oxidative stress and thus represses the POF phenotype. Oxr1a was widely expressed in oocytes at different developmental stages, of which the mRNA expression levels were significantly upregulated upon follicle activation and oocyte maturation. Oxr1a knockout exacerbated the POF phenotype, as evidenced by the decreased number and quality of oocytes. Moreover, the oocytes of oxr1a knockout zebrafish exhibited excessive ROS, increased mitochondrial DNA damage, reduced mitochondria, and abnormal morphology. Mechanistically, instead of decomposing ROS directly, Oxr1a participated in the process of oxidative stress through regulating the mRNA expression levels of the key antioxidant enzymes Cat and Sod1. Moreover, treatment with antioxidant N-Acetyl-l-cysteine attenuated the mitochondrial oxidative damage and improved the fertility of mutant females, indicating that Oxr1a may mediates the Sod1/Cat pathway to metabolize the intracellular ROS and avoid the mitochondrial oxidative damage, thus ensuring the normal development and maturation of oocytes. Taken together, these findings are useful for the elucidation of molecular mechanisms underlying the oxidative damage in oocytes and beneficial to the clinical therapeutics of POF.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Zebrafish
/
Primary Ovarian Insufficiency
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Free Radic Biol Med
Journal subject:
BIOQUIMICA
/
MEDICINA
Year:
2023
Type:
Article