Profile of apoptotic and cell cycle genes in the follicular fluid of patients with the empty follicle syndrome who is treated by GnRH antagonist protocol

Background: Alternation of follicular fluid component induced by paracrine, and autocrine signaling pathways may influence the oocyte quality. Various genetic factors have been previously demonstrated for the development of empty follicle syndrome (EFS).Objective: Present study aimed to investigate gene expression profiles of apoptosis and cell cycle pathways using microarray technique in the follicular fluid (FF) of 10 patients with genuine EFS (GEFS) undergoing GnRH antagonist protocol.Materials and Methods: In this randomized clinical trial study, FF of the empty follicles were collected from 10 infertile women following first and second triggering with hCG. RNA was extracted from the FF samples containing oocytes and without oocytes for gene expression analyses. PCR arrays were performed to evaluate gene expression profiles related to the apoptosis and cell cycle pathways. PCR array validation was carried out by qPCR.Results: Remarkable alternation were observed in the apoptotic gene expression including BCL2, COMP, GADD45A, IL1B, MSX1, TNF and TNFRSF10B in the FF from patients who had oocytes retrieved when compared to the group without oocyte. Moreover, differentially expression of genes related to the cell cycle pathway comprising CCNB1, GADD45A, MKI67, STMN1 and TGFBβ1 were detected in the patients who had oocytes retrieved in comparison to those without oocyte. Changes in the gene expression of both two pathways quantified by q RT-PCR were in agreement with the microarray findings. This study demonstrated that aberrant apoptosis and cell cycle signaling molecules expression might be considered as a genetic basis for EFS.Conclusion: Therefore, it can be concluded that properly function of these genes within the apoptosis and cell cycle pathways might culminate to the final maturation of oocytes which is required for a successful fertilization in IVF treatment.

Keywords:

Empty follicle syndrome , Apoptosis , Cell cycle , Antagonist protocol , PCR array , Follicular fluid , Oocyte