Circular RNA expression profiling and the potential role of hsa_circ_0005379 in decreased ovarian reserve

Decreased ovarian reserve (DOR) refers to the decreased ability of the ovaries to produce eggs and the low quality of the follicles, which may lead to abnormal menstruation and infertility. However, the role of circular RNAs (circRNAs) in DOR remains poorly understood. Through circRNA sequencing, hsa_circ_0005379 was identified as the most significantly upregulated circRNA in the follicular fluid exosomes of patients with DOR. The present study aimed to characterize the circRNA expression profile and investigate the function of hsa_circ_0005379 in DOR. Exosomes were isolated from the follicular fluid of individuals with DOR and healthy controls, followed by sequencing using the Illumina HiSeq platform. Functional enrichment analysis, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis, was performed on the differentially expressed circRNAs. To further validate the results, the expression of five circRNAs was assessed in follicular fluid via reverse transcription-quantitative PCR (RT-qPCR). A DOR cell model was established by treating KGN granulosa cells with cyclophosphamide (CTX). Cell viability was evaluated using a Cell Counting Kit-8 assay following CTX exposure. hsa_circ_0005379 was either overexpressed or knocked down in the CTX-treated cells, and the levels of cell apoptosis, reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) were analyzed by flow cytometry and biochemical assays. Eight differentially expressed circRNAs were identified in individuals with DOR compared with controls, including seven upregulated and one downregulated. RT-qPCR confirmed that the expression trends of hsa_circ_0000344, hsa_circ_0001126, hsa-circ_0005379, hsa_circ-0005777 and hsa_circ_0007509 aligned with those from the sequencing results. Furthermore, overexpression and knockdown of hsa_circ_0005379 in KGN cells was verified by RT-qPCR. Silencing hsa_circ_0005379 in CTX-treated KGN cells promoted cell viability and reduced apoptosis, accompanied by reduced ROS and MDA levels and enhanced SOD activity. Overexpression of hsa_circ_0005379 yielded the opposite results. Collectively, the results suggested that hsa_circ_0005379 played a key role in regulating cell viability and oxidative stress in CTX-treated granulosa cells.