Division of Human Reproduction, IVF Unit, 1st Department of Obstetrics and Gynaecology, Alexandra Hospital, Athens University Medical School, 80 Vasilissis Sofias Avenue, 11528, Athens, Greece.
J Assist Reprod Genet. 2012 May;29(5):409-16. doi: 10.1007/s10815-012-9729-7. Epub 2012 Mar 1.
Luteinizing hormone (LH) exerts its actions through its receptor (LHR), which is mainly expressed in theca cells and to a lesser extent in oocytes, granulosa and cumulus cells. The aim of the present study was the investigation of a possible correlation between LHR gene and LHR splice variants expression in cumulus cells and ovarian response as well as ART outcome.
Forty patients undergoing ICSI treatment for male factor infertility underwent a long luteal GnRH-agonist downregulation protocol with a fixed 5-day rLH pre-treatment prior to rFSH stimulation and samples of cumulus cells were collected on the day of egg collection. RNA extraction and cDNA preparation was followed by LHR gene expression investigation through real-time PCR. Furthermore, cumulus cells were investigated for the detection of LHR splice variants using reverse transcription PCR.
Concerning LHR expression in cumulus cells, a statistically significant negative association was observed with the duration of ovarian stimulation (odds ratio = 0.23, p = 0.012). Interestingly, 6 over 7 women who fell pregnant expressed at least two specific types of LHR splice variants (735 bp, 621 bp), while only 1 out of 19 women that did not express any splice variant achieved a pregnancy.
Consequently, the present study provide a step towards a new role of LHR gene expression profiling as a biomarker in the prediction of ovarian response at least in terms of duration of stimulation and also a tentative role of LHR splice variants expression in the prediction of pregnancy success.
黄体生成素(LH)通过其受体(LHR)发挥作用,LHR 主要在卵泡膜细胞中表达,在卵母细胞、颗粒细胞和卵丘细胞中表达较少。本研究旨在探讨卵丘细胞中 LHR 基因及其剪接变异体表达与卵巢反应和 ART 结局之间的可能相关性。
40 名因男性因素不孕接受 ICSI 治疗的患者接受了长黄体期 GnRH 激动剂下调方案,在 rFSH 刺激前进行了 5 天的 rLH 预处理,并在取卵日采集了卵丘细胞样本。进行 RNA 提取和 cDNA 制备后,通过实时 PCR 研究 LHR 基因表达。此外,通过逆转录 PCR 研究卵丘细胞中 LHR 剪接变异体的检测。
关于卵丘细胞中 LHR 的表达,与卵巢刺激持续时间呈统计学显著负相关(优势比=0.23,p=0.012)。有趣的是,6 名怀孕的女性中至少有两种特定类型的 LHR 剪接变异体(735 bp、621 bp)表达,而 19 名未表达任何剪接变异体的女性中只有 1 名怀孕。
因此,本研究为 LHR 基因表达谱作为预测卵巢反应的生物标志物提供了一个新的研究方向,至少在刺激持续时间方面,以及 LHR 剪接变异体表达在预测妊娠成功方面的初步作用。