Impacts of vitrification on the transcriptome of human ovarian tissue in patients with gynecological cancer

Abstract

Objective: This study investigated the effects of a vitrification/warming procedure on the mRNA transcriptome of human ovarian tissues.Design: Human ovarian tissues were collected and processed through vitrification (T-group) and then subjected to RNA sequencing (RNA-seq) analysis, HE, TdT-mediated dUTP nick-end labeling (TUNEL), and real-time quantitative PCR, and the results were compared to those of the fresh group (CK).Results: A total of 12 patients, aged 15–36 years old, with a mean anti-Müllerian hormone level of 4.57 ± 3.31 ng/mL were enrolled in this study. According to the HE and TUNEL results, vitrification effectively preserved human ovarian tissue. A total of 452 significantly dysregulated genes (|log2FoldChange| > 1 and p < 0.05) were identified between the CK and T groups. Among these, 329 were upregulated and 123 were downregulated. A total of 372 genes were highly enriched for 43 pathways (p < 0.05), which were mainly related to systemic lupus erythematous, cytokine–cytokine receptor interaction, the TNF signaling pathway, and the MAPK signaling pathway. IL10, AQP7, CCL2, FSTL3, and IRF7 were significantly upregulated (p < 0.01), while IL1RN, FCGBP, VEGFA, ACTA2, and ASPN were significantly downregulated in the T-group (p < 0.05) compared to the CK group, which agreed with the results of the RNA-seq analysis.Conclusion: These results showed (for the first time to the authors’ knowledge) that vitrification can induce changes in mRNA expression in human ovarian tissues. Further molecular studies on human ovarian tissues are required to determine whether altered gene expression could result in any downstream consequences.

Current Fertility Preservation Steps in Young Women Suffering from Cancer and Future Perspectives

“…Other pathways associated with reproduction are the ECM-receptor interaction, focal adhesion, and Jak-STAT. Gu et al [53] demonstrated that the cryopreservation process can activate or deactivate these physiological functions. However, once ovarian grafts were able to support complete oocyte growth, the dysregulation of genes could be associated with a compensatory mechanism to maintain ovarian viability after vitrification, which qualitatively did not impair oogenesis.…”

Cryopreservation of Ovarian and Testicular Tissue and the Influence on Epigenetic Pattern

“…In general, cryopreservation of ovarian tissue can result in changes in gene expression and protein abundance at different stages [ 48 , 49 ]. More precisely, cryopreservation also hampers several specific epigenetically relevant factors ( Table 1 ).…”

Innovative Strategies for Fertility Preservation in Female Cancer Survivors: New Hope from Artificial Ovary Construction and Stem Cell-Derived Neo-Folliculogenesis

“…Interestingly, a recently published systematic review and meta-analysis has reported a significantly greater proportion of intact stromal cells in vitrified tissue versus slow-frozen tissue, with no significant differences with respect to the proportion of intact primordial follicles, extent of DNA fragmentation, or mean primordial follicle density [20]. Conversely, some reports suggested that vitrification may induce changes in mRNA expression and delayed growth of follicles in vitro in human ovarian tissues [21,22].…”