Division of Human Reproduction, IVF Unit, 1st Department of Obstetrics and Gynaecology, Alexandra Hospital, Athens University Medical School, Athens, Greece.
Reprod Biol Endocrinol. 2012 Nov 28;10:99. doi: 10.1186/1477-7827-10-99.
RUNX2 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.
A 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.
Concerning 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).
Consequently, 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.
RUNX2 是一种转录因子,其在小鼠卵巢中的表达最近被鉴定出来。RUNX2 表达的调节及其在人卵巢中的功能尚未确定。本研究的目的是探讨卵丘细胞中 RUNX2 基因表达与控制性卵巢刺激和 ART 治疗后妊娠结局之间的可能相关性。
共纳入 41 名因男性因素不孕接受 ICSI 治疗的患者进入特定的 ART 方案,在此期间收集卵丘细胞。通过实时 PCR 检查卵丘细胞中 RUNX2 基因的表达。
在 41 名女性中,有 12 名检测到 RUNX2 基因表达,比值范围为 0.84 至 1.00,而 28 名女性无表达(比值=0)。只有 1 名女性呈现弱 RUNX2 基因表达(比值=0.52)。在 8 名成功妊娠的女性中,有 7 名女性的卵丘细胞中没有 RUNX2 基因表达,而一名呈现弱基因表达的女性也成功妊娠。无 RUNX2 表达的女性组卵泡数较多(p=0.013),获卵数较多(p=0.016),基础 LH 血清水平较高(p=0.016),峰值雌二醇水平较高(p=0.013),而两组受精卵数差异较小(p=0.089)。此外,RUNX2 表达与 LH 水平呈负相关(OR=0.22,p=0.021),与 E2 水平呈负相关(OR=0.25,p=0.026)。
因此,基于本初步研究的初步发现,当检测到高 mRNA 水平时,卵巢中观察到 RUNX2 基因的潜在抑制机制,表明 RUNX2 可能可用作 ART 治疗结局监测的候选遗传标志物。