INVESTIGATION OF ENDOPLASMIC RETICULUM SIGNAL PROTEINS IN CUMULUS CELLS WITH NORMAL,HYPERRESPONSIVE,HYPORESPONSIVE AND POLYCYSTIC OVARY SYNDROMES

Abstract

The aim of the study was to investigate Endoplasmic reticulum dependent Unfolded Protein Response signal molecules in cumulus cells of the patients presenting normal, hyperresponsive, hyporesponsive, and polycystic ovary syndrome . Cumulus cells were provided during oocyte retrieval. Of the patients applying for in vitro fertilization treatment, three subtypes of patient groups were distinguished according to their response to follicle stimulations. The first group composed of normoresponsive (n=8) was considered as retrieval of 10-20 oocytes. The second group composed of hyporesponsive (n=8) as retrieval of 6 or less oocytes. Retrieval of 30 or more oocytes as a response to the same stimulus was considered hyperrespponsive (n=8), which included polycyctıc ovary sydromes. (n=8). We analyzed the protein expressions of glucose regulated protein 78 and mRNAs levels of the X-box binding protein-1 and splicing X-box binding protein-1 by Western blot and Reverse Transcriptase PCR, respectively ,in the CCs from different patient groups. All data were loaded to the software Sigma Stat 3. Differences between groups were evaluated with one-way ANOVA post hoc TURKEY test. We found that the protein expression of glucose regulated protein 78 was two fold higher in cumulus cells from hyporesponsive group than the other groups. Reverse Transcriptase PCR results showed us, the mRNA expression of splicing X-box / X-box binding protein-1 level was 1,5 fold higher in the cumulus cells from the hyporesponsive group compared to others. Furthermore, we have shown that when the cumulus cells were exposed to signal pathway molecules that related with ER stress; a decrease in the cell proliferation and/or increase in apoptosis can occured. We have shown that an increased ER stress in the cumulus cells of the ovarian follicle from the patients forming the hyporesponsive group. We can concluded that increased ER stress or impaired protein folding mechanism in cumulus cells may affect oocyte maturation therefore the agents may be used to decrease pathological ER stress in the hyporesponsive patients.

Keywords

• endoplasmic reticulum stress
• unfolded protein response