Abstract
BackgroundMaternal oocyte aging is strongly contributing to age-related decline in female fertility. Coenzyme Q10 (CoQ10) exerts positive effects in improving aging-related deterioration of oocyte quality, but the exact mechanism is unclear.ObjectiveTo reveal the system-level mechanism of CoQ10’s anti-aging effect on oocytes based on network pharmacology.MethodsThis study adopted a systems network pharmacology approach, including target identification, data integration, network and module construction, bioinformatics analysis, molecular docking, and molecular dynamics simulation.ResultA total of 27 potential therapeutic targets were screened out. Seven hub targets (PPARA, CAT, MAPK14, SQSTM1, HMOX1, GRB2, and GSR) were identified. Functional and pathway enrichment analysis indicated that these 27 putative targets exerted therapeutic effects on oocyte aging by regulating signaling pathways (e.g., PPAR, TNF, apoptosis, necroptosisn, prolactin, and MAPK signaling pathway), and are involved oxidation-reduction process, mitochondrion, enzyme binding, reactive oxygen species metabolic process, ATP binding, among others. In addition, five densely linked functional modules revealed the potential mechanisms of CoQ10 in improving aging-related deterioration of oocyte quality are closely related to antioxidant, mitochondrial function enhancement, autophagy, anti-apoptosis, and immune and endocrine system regulation. The molecular docking study reveals that seven hub targets have a good binding affinity towards CoQ10, and molecular dynamics simulation confirms the stability of the interaction between the hub targets and the CoQ10 ligand.ConclusionThis network pharmacology study revealed the multiple mechanisms involved in the anti-aging effect of CoQ10 on oocytes. The molecular docking and molecular dynamics simulation provide evidence that CoQ10 may act on these hub targets to fight against oocytes aging.
Highlights
Aging leads to a gradual and continuous decline of physiological processes
The GSE95477 data set derived from the GEO database was analyzed and 61 Differentially expressed gene (DEG) were obtained according to the cut-off criteria. 1455 DEGs of GSE155179 date are obtained via the same method
We re-screened DEGs according to the cut-off criteria and obtained 1439 DEGs
Summary
Aging leads to a gradual and continuous decline of physiological processes. Oogenesis is one of the first processes to fail during human aging. Human oocyte development begins in the early fetal life, reaches its peak at 20 weeks of gestation, and remains dormant before complete meiosis I [1]. The quality and quantity of these oocytes gradually declined, concurrently with the reduced reproductive ability and increased occurrence of aneuploidy, miscarriage, and birth defects [2–4]. The aging-related decline in fecundity was negated in patients using oocytes obtained from healthy young donors [5]. These data suggest that the age-related decline in fertility is strongly attributed to a decline in the oocyte quality. Maternal oocyte aging is strongly contributing to age-related decline in female fertility. Coenzyme Q10 (CoQ10) exerts positive effects in improving aging-related deterioration of oocyte quality, but the exact mechanism is unclear
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