Abstract
It is well known that chemotherapeutic agents may lead to premature ovarian failure and infertility. Therefore, fertility preservation is highly recommended for female cancer survivors. Despite the currently available techniques, new, non-invasive methods need to be developed to protect the ovarian follicles during oncological treatments. MicroRNAs can be effective tools in this field, as they alter their expression during chemotherapy exposure, and hence they can be useful to minimize the off-target toxicity. Previously, we identified several miRNAs with an important role in newborn mouse ovaries exposed to chemotherapy; among them, the miR-10a was one of the most downregulated miRNAs. Given the controversial role of miR-10a in the ovarian function, we decided to investigate its implication in chemotherapy-induced gonadotoxicity. The downregulated levels of miR-10a were restored by a liposome system conjugated with a mimic miR-10a, and the overexpressed miR-10a prevented the upregulation of the targeted gene, phosphatase and tensin homolog (Pten). The apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) Assay and Bax expression quantification, while histological studies were also performed to evaluate the follicle count and development. Our results showed that the miR-10a replacement could not protect the ovaries from chemotherapy-induced apoptosis, whereas the targeting of Pten may affect the follicle activation via the phosphoinositide 3-kinase (PI3K)/PTEN/protein kinase B (AKT) pathway. Consequently, the application of miR-10a in fertility preservation is not recommended, and the role of miR-10a needs to be further elucidated.
Highlights
Cancer is the second leading cause of death globally, and according to the latest global cancer data of the World Health Organization (WHO), one in six women develop cancer during their lifetime worldwide
MiRNAs have tissue-specific, and cell-specific expression profiles, while one miRNA can modulate the expression of several genes, which gives the opportunity of selective and expanded targeting at the same time [12,13]. These targets may be involved in different cellular processes such as DNA damage response (DDR), apoptosis, and follicle activation, which are mainly triggered by chemotherapeutic treatments in the ovary [14,15,16]
Our findings indicate that miR-10a does not offer ovarian protection against chemotherapy-induced damage, and we question its safety regarding the future clinical applications in fertility preservation
Summary
Cancer is the second leading cause of death globally, and according to the latest global cancer data of the World Health Organization (WHO), one in six women develop cancer during their lifetime worldwide. MiRNAs have tissue-specific, and cell-specific expression profiles, while one miRNA can modulate the expression of several genes, which gives the opportunity of selective and expanded targeting at the same time [12,13] These targets may be involved in different cellular processes such as DNA damage response (DDR), apoptosis, and follicle activation, which are mainly triggered by chemotherapeutic treatments in the ovary [14,15,16]. The transfection of miR-10a led to a significant decrease in the percentage of cells expressing proliferation markers; proliferating cell nuclear antigen (PCNA), cyclin B1 (CCNB1) and to an increase in cells expressing apoptotic markers Bcl-2-associated X protein (BAX), terminal deoxynucleotidyl transferase (TDT), cysteine-aspartic acid protease-3 (CASPASE-3) Aiming to elucidate this controversy and draw conclusions about the potential protective effect of miR-10a, we investigated the role of miR-10a in the protection of newborn mouse ovaries against cyclophosphamide-induced apoptosis. Our findings indicate that miR-10a does not offer ovarian protection against chemotherapy-induced damage, and we question its safety regarding the future clinical applications in fertility preservation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
