Chen Guowu, Xin Aijie, Liu Yulin, Shi Changgen, Chen Junling, Tang Xiaofeng, Chen Ying, Yu Min, Peng Xiandong, Li Lu, Sun Xiaoxi
Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China.
Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, 200011, China.
J Transl Med. 2016 Oct 26;14(1):303. doi: 10.1186/s12967-016-1052-0.
Clinical ovulation induction induces blood estrogen (E) in excess of physiological levels, which can hinder uterine receptivity. In contrast, progesterone produces the opposite clinical effect, suggesting that it might be capable of recovering the lost receptivity resulting from exposure to high estrogen levels. Integrins are the most widely used biological markers for monitoring uterine conditions. We studied progesterone-induced changes in integrin β expression patterns as biomarkers for changes in uterine receptivity in response to increased estrogen levels.
Endometrial biopsy samples from patients were screened for their estrogen (E) and progesterone (P4) content and expressing levels of integrin β1 and β3. Uterine receptivity was evaluated using human endometrial adenocarcinoma cells in an embryo attachment model. The respective and concatenated effects of embryo attachment and changes in the integrin β1 and β3 expression patterns on the adenocarcinoma cell plasma membranes in response to 100 nM concentrations of E and P4 were evaluated.
Increased blood E concentrations were associated with significantly decreased the levels of integrin β3 expression in uterine biopsy samples. In vitro experiments revealed that a 100 nM E concentration inhibited the distribution of integrin β3 on the plasma membranes of human endometrial adenocarcinoma cells used in the embryo attachment model, and resulted in decreased rates of embryo attachment. In contrast, P4 enhanced the expression of integrin β1 and promoted its distribution on the plasma membranes. Furthermore, P4 recovered the embryo attachment efficiency that was lost by exposure to 100 nM E.
Blood E2 and P4 levels and integrin β3 and β1 expression levels in uterine biopsy samples should be considered as biomarkers for evaluating uterine receptivity and determining the optimal time for embryo transfer. Trial registration Trial number: ChiCTR-TRC-13003777; Name of registry: Chinese Clinical Trial Registry; Date of registration: 4 September 2013; Date of enrollment of the first study participant: 15 October 2013.
临床促排卵会使血液中的雌激素（E）超过生理水平，这可能会妨碍子宫容受性。相比之下，孕激素产生相反的临床效果，这表明它可能能够恢复因暴露于高雌激素水平而丧失的容受性。整合素是监测子宫状况最广泛使用的生物标志物。我们研究了孕激素诱导的整合素β表达模式的变化，作为子宫对雌激素水平升高反应时容受性变化的生物标志物。
对患者的子宫内膜活检样本进行雌激素（E）、孕激素（P4）含量以及整合素β1和β3表达水平的筛查。在胚胎着床模型中，使用人子宫内膜腺癌细胞评估子宫容受性。评估了100 nM浓度的E和P4对胚胎着床以及整合素β1和β3在腺癌细胞质膜上表达模式变化的各自及联合作用。
血液中E浓度升高与子宫活检样本中整合素β3表达水平显著降低相关。体外实验表明，100 nM的E浓度抑制了整合素β3在胚胎着床模型中所用的人子宫内膜腺癌细胞质膜上的分布，并导致胚胎着床率降低。相比之下，P4增强了整合素β1的表达并促进其在质膜上的分布。此外，P4恢复了因暴露于100 nM E而丧失的胚胎着床效率。
子宫活检样本中的血液E2和P4水平以及整合素β3和β1表达水平应被视为评估子宫容受性和确定胚胎移植最佳时间的生物标志物。试验注册 试验编号：ChiCTR - TRC - 13003777；注册机构名称：中国临床试验注册中心；注册日期：2013年9月4日；首例研究参与者入组日期：2013年10月15日。
