Abstract
BackgroundRUNX2 is a transcription factor, whose expression has been recently identified in the mouse ovary. Regulation of RUNX2 expression and its function in the human ovary have not been determined yet. The aim of the present study is the investigation of the possible correlation between RUNX2 gene expression in cumulus cells and controlled ovarian stimulation and pregnancy outcomes after ART treatment.MethodsA total of 41 patients undergoing ICSI treatment for male factor infertility were enrolled into a specific ART program, during which cumulus cells were collected. The expression of RUNX2 gene in cumulus cells was examined by real-time PCR.ResultsConcerning RUNX2 gene expression, 12 out of 41 women were detected with RUNX2 expression, with ratios ranging from 0.84 to 1.00, while 28 out of 41 women had no expression (ratio = 0). Only 1 woman presented a weak RUNX2 gene expression (ratio = 0.52). From 8 women that proceeded to pregnancy, 7 of them did not express RUNX2 gene in cumulus cells, while one was the woman with weak gene expression that also achieved pregnancy. The group of women without RUNX2 expression presented higher number of follicles (p = 0.013), higher number of retrieved oocytes (p = 0.016), higher basal LH serum levels (p = 0.016) and higher peak estradiol levels (p = 0.013), while the number of fertilized oocytes differed marginally between the two groups (p = 0.089). Moreover, RUNX2 expression was negatively associated with LH levels (OR = 0.22, p = 0.021) and E2 levels (OR = 0.25, p = 0.026).ConclusionsConsequently, based on the preliminary findings of the present pilot study a potential inhibitory mechanism of RUNX2 gene is observed in the ovary when high mRNA levels are detected, suggesting that RUNX2 could possibly be used as a candidate genetic marker in the monitoring of the outcome of an ART treatment.
Highlights
RUNX2 is a transcription factor, whose expression has been recently identified in the mouse ovary
It is well known that assisted reproductive technology (ART) treatment is a successful approach for infertile couples, which commonly overcomes the underlying infertility causes resulting in significantly higher pregnancy rates compared to natural conception
Due to the deviation from normality, non-parametric Mann–Whitney test was applied in order to evaluate the univariate association of demographic and biochemical factors, as well as factors included in the ovarian stimulation profile of each patient and RUNX2 gene expression in cumulus cells
Summary
RUNX2 is a transcription factor, whose expression has been recently identified in the mouse ovary. RUNX2 (Cbfa, AML-3, PEBP2αA) is well known for regulating both intramembranous and endochondral bone formation, as well as osteoblast development and differentiation and chondrocyte differentiation. It is a member of the runt family of transcription factors. RUNX2 gene is located on chromosome 6, consists of eight coding exons and spans a genomic region of 130 kb. It contains a DNA-binding domain, a region of glutamine and alanine repeats in the N-terminal region and a region rich in proline-serinethreonine, which is necessary for transcriptional activation of target genes [3]. RUNX2 association with the nuclear domain facilitates interaction with many co-regulatory proteins and chromatin-modifying complexes for the regulation of gene transcription [4]
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