Marcador de células-tronco SOX2 é amplamente expresso em células da granulosa luteinizada humana de mulheres submetidas à estimulação ovariana controlada

Abstract

The human ovary is responsible for providing mature and competent reproductive oocytes and contains cells that exhibit stem cell markers, including a subpopulation of granulosa cells (GC). Inhibins can be considered a marker of follicular activity and ovarian reserve. There is evidence that less differentiated cells with stem cell characteristics may indicate abnormalities of ovarian function that lead to infertility. SOX2 is a transcription factor that determines the fate of stem cells, acting as an activator or suppressor of genes involved in cell differentiation, proliferation, and apoptosis. This study aimed to evaluate the gene and protein expression of SOX2 and alpha-inhibin in the luteinized granulosa (hGC) cells of patients submitted to controlled ovarian stimulation (COS) and the correlation with the total number of oocytes, the number of mature oocytes collected, among other clinical parameters. Thirty-two women who underwent HOC for in vitro fertilization were prospectively included in the study. GC was isolated from the follicular fluid. The protein and gene expression of SOX2 and alpha-inhibin were evaluated in GC by ICC (Cell Block) and qPCR. The results demonstrated positive immunostaining for alpha-inhibin and SOX2 in CGL in all patients, and positive SOX2 nuclear was observed in most cells (95%), predominantly cells with strong nuclear staining (64.2 %). In addition, positive cytoplasmic staining with alpha-inhibin in CGL was observed in all cases, with an average of 66% of positive cells (40.6% with strong staining, 25.7% with weak and moderate staining). Accordingly, the expression of alpha-inhibin mRNA was detected in all patients' CGL. However, the SOX2 nuclear immunolocalization did not correlate with the number of punctured oocytes and their maturation. It did not indicate a correlation with the clinical parameters of patients undergoing COS. However, for the first time, extensive SOX2 nuclear immunolocalization in LGC was observed. Yet, even without any significant clinical correlation of SOX2 staining, the wide expression of SOX2 indicates the granulosa cells' potential to differentiate into other cell types and its potential use in regenerative medicine.