Comparison of Notch1-3, genes expression and Jagged-1,2 proteins in cumulus cells of PCOS and healthy women’s and their correlations with oocyte, fertilization and embryo

Background: Bi-directional communication between the oocyte and cumulus cells is essential for the production of competent oocytes and corresponding embryos. In this regard, apoptosis of cumulus cells has a negative effect on oocyte and embryo quality. One of the signaling pathways that plays important roles in maintaining of differentiated cells and reducing apoptosis is the Notch pathway, but so far, little is known about this signaling pathway in cumulus cells and its correlation with the oocyte and embryo in patients with polycystic ovary syndrome.Objective: To investigate associations between gene expression pattern of Notch signaling receptors and its ligands in cumulus cells of polycystic ovary syndrome (PCOS) patients and the quality of oocytes, zygotes and embryos.Materials and Methods: 40 intracytoplasmic sperm injection (ICSI) patients, of whom 20 were PCOS and 20 were healthy women, included in this study. Serum hormone levels were measured by using Radioimmunoassay (RIA) for each patient. The expression of NOTCH1, NOTCH2 and, NOTCH3 in 200 cumulus complexes surrounding mature oocytes was examined by real-time polymerase chain reaction (real-time PCR). Further, immunohistochemistry was performed for Jagged-1 and Jagged-2 proteins.Results: The expression levels of Notch pathway genes and proteins including NOTCH 2,3, and Jagged-1, Jagged-2 proteins were significantly different between groups) p˂0.05. (There was a statistically positive significant correlation between the level of NOTCH-2 and zygote quality (r=0.802, p=0.042). In addition, there were positive correlations between NOTCH1-3 and embryo quality (r=0.445, p=0.005, r=0.311, p=0.058, r=0.332, p=0.042). There were no correlations between Jagged-1 and Jagged-2 expressions and oocyte quality (p> 0.05) while Jagged-2 showed a negative correlation with zygotes with Z3 grade (r=-0.128, p=0.044). In addition, Jagged-2 showed a positive correlation with top embryo quality (r=0.199, p=0.023) and negative correlation with embryo with grade2(r=-0.320, p=0.051).Conclusion: This study reveals that the measurement of Notch pathway genes and proteins levels in cumulus cells could be used as genetic biomarkers for oocyte and embryo selection under an ART program.

Keywords:

PCOS , Oocyte quality , Embryo quality , Zygote quality , Cumulus cells