Colorado Foundation for Fertility Research, Lone Tree, Colorado, USA.
Fertil Steril. 2011 Mar 15;95(4):1367-72. doi: 10.1016/j.fertnstert.2010.08.009. Epub 2010 Sep 22.
To investigate the role of the blastocyst in implantation failure. This study examined trophectoderm (TE) gene expression relative to pregnancy outcome.
Retrospective experimental study.
Nonprofit research foundation.
ANIMAL(S): Six-week-old BDF1 female mice.
INTERVENTION(S): Hatching blastocysts underwent trophectoderm biopsy before single blastocyst transfer (one per uterine horn).
Blinded gene expression analysis was performed on biopsied TE cells by quantitative real-time polymerase chain reaction (Q RT-PCR). Healthy placenta and absorption sites were biopsied on day 16 of fetal development for comprehensive transcriptome analysis with validation by Q RT-PCR.
RESULT(S): Compared with blastocysts that resulted in healthy fetal development, blastocysts that failed to implant (negative) showed decreased B3gnt5 and Eomes gene expression, while blastocysts that resulted in spontaneous pregnancy loss (absorption) displayed decreased Wnt3a and Eomes gene expression. Comprehensive transcriptome analysis of biopsied absorption sites and healthy placenta revealed distinct gene expression signatures, with 5,918 significantly altered transcripts (greater than twofold). The predominantly altered pathways associated with spontaneous pregnancy loss were the complement and coagulation cascades.
CONCLUSION(S): This study revealed for the first time that individual blastocyst gene expression profiles correlate with outcome, including successful implantation and pregnancy loss.
研究囊胚在着床失败中的作用。本研究检查了滋养外胚层(TE)基因表达与妊娠结局的关系。
回顾性实验研究。
非营利性研究基金会。
6 周龄 BDF1 雌性小鼠。
孵育囊胚在单个囊胚转移(每个子宫角一个)前进行滋养外胚层活检。
通过定量实时聚合酶链反应(Q RT-PCR)对活检的 TE 细胞进行盲法基因表达分析。在胎儿发育第 16 天,对健康胎盘和吸收部位进行活检,进行全面转录组分析,并通过 Q RT-PCR 进行验证。
与导致健康胎儿发育的囊胚相比,未能着床(阴性)的囊胚显示 B3gnt5 和 Eomes 基因表达降低,而导致自发性妊娠丢失(吸收)的囊胚显示 Wnt3a 和 Eomes 基因表达降低。对活检的吸收部位和健康胎盘进行全面转录组分析显示出明显的基因表达特征,有 5918 个明显改变的转录本(大于两倍)。与自发性妊娠丢失相关的主要改变途径是补体和凝血级联。
本研究首次表明,单个囊胚的基因表达谱与结局相关,包括成功着床和妊娠丢失。