Vaginal bioelectrical impedance determines uterine receptivity in mice

Vaginal bioelectrical impedance determines uterine receptivity in mice
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阴道生物电阻抗决定小鼠子宫容受性

DOI:
10.1093/humrep/dey313
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发表时间:
2018
期刊:
影响因子:
6.1
通讯作者:
T.
T.
中科院分区:
医学1区
文献类型:
--
作者:
Nakamura;H. Hosono;T. Kumasawa;K. Jones;C. J. P. Aplin;J. D. Kimura;T.

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研究问题阴道生物电阻抗(VZ)能否从电生理学的角度决定着床准备过程中子宫内膜的变化?概述ANSWERVZ可以电生理地检测子宫糖萼在植入准备过程中的硫酸盐化和唾液酸化的变化。已知ALREADYUTURE的容受性与影响子宫腔上皮细胞表面负电荷密度的各种糖基化变化有关。VZ用于监测发情周期。研究设计、大小、形状。无病原体JCL:ICR小鼠,8-10周龄。我们进行了以下三个步骤来验证我们的假设,即VZ可能被用来确定子宫容受性。首先,为了研究VZ是否可以确定子宫糖萼中硫酸盐化和唾液酸化的变化,测定了人工硫化和唾液酸化改变的小鼠子宫糖萼(半乳糖-3-O-磺酸转移酶2(GP3ST)+α(1,3/1,4)岩藻糖基转移酶基因(FUCT-III)转染组(n=15)和转导LacZ(编码β-半乳糖苷酶)的小鼠(n=12))中的VZ。其次,为了研究VZ是否可以在植入准备过程中确定子宫内膜的变化,我们测量了妊娠早期的VZ(n=12)。第三,为了研究VZ是否可以用于前瞻性地评估子宫容受性,在一种植入失败模型小鼠中测量了VZ。21只小鼠在植入前1天检测子宫内信号转导和转录激活因子3(STAT3)的局部和瞬时抑制情况,23只杂乱诱骗转移的小鼠作为对照组。数据分析使用Kruskal-Wallis检验和Dunn的多重比较,或学生的st检验或Wilcoxon的秩和检验和Shapiro-Wilk正态检验。用受试者工作特征(ROC)曲线分析VZ的值,以确定最佳的截断点,以确定该参数是否预示无妊娠。VZ在怀孕早期表现出每天显著的下降(第1.5天对2.5P.C.:P<0.005;学生ST-test,第2.5d对3.5P.C.:P<0.001;Wilcoxon‘s秩和检验,第3.5d对4.5P.C.:P<0.005;学生ST-test,第4.5d对5.5P.C.:P<0.05;学生’st-test)。在植入开始前一天,植入失败模型组小鼠的VZ显著高于对照组(P<0.001,Wilcoxon‘s秩和检验)。ROC曲线分析显示VZ作为未受孕的预测因子的ROC曲线下面积为0.91(95%CI:0.83-0.99)。限制,原因虽然VZ受子宫上皮表面电荷的影响,但VZ在妊娠早期变化的机制仍不清楚。FINDINS局部生物电阻抗的广泛意义可能有助于前瞻性评估妇女的子宫容受性。将局部生物电阻抗的测量作为冷冻解冻胚胎移植策略的一部分,可能会提高ART的效率。研究资金/竞争兴趣(S)这项工作部分得到了…的支持
STUDY QUESTIONCan vaginal bioelectrical impedance (VZ) electrophysiologically determine alterations of the endometrium in preparation for implantation?SUMMARY ANSWERVZ can electrophysiologically detect the sulfation and sialylation changes in the uterine glycocalyx in preparation for implantation.WHAT IS KNOWN ALREADYUterine receptivity is associated with various glycosylation changes that affect negative charge density at the luminal epithelial cell surface. VZ has been used to monitor the oestrous cycle.STUDY DESIGN, SIZE, DURATIONPathogen-free Jcl:ICR mice, aged 8–10 weeks, were used in this study. We conducted the following three steps to test our hypothesis that VZ may be used to determine uterine receptivity. First, to investigate whether VZ could determine alteration of sulfation and sialylation in the uterine glycocalyx, VZ was measured in mice with induced artificial sulfation and sialylation changes in the uterine glycocalyx (galactose-3-O-sulfotransferase 2 (GP3ST) + α(1,3/1,4) fucosyltransferase gene (FucT-III)-transferred group (n= 15) and in LacZ (encoding for β-galactosidase)-transferred mice as a control group (n= 12)). Second, to investigate whether VZ could determine alterations of the endometrium in preparation for implantation, we measured VZ during the early stage of pregnancy (n= 12 each). Third, to investigate whether VZ could be used to evaluate uterine receptivity prospectively, VZ was measured in an implantation failure model mice. In 21 mice, local and transient suppression of signal transducer and activator of transcription-3 (Stat3) in the uterus were evaluated 1 day before implantation began, and 23 scramble decoy-transferred mice were used as a control group.PARTICIPANTS/MATERIALS, SETTING, METHODSThe VZ was measured at a frequency of 1 kHz in Jcl:ICR mice. Data were analysed using the Kruskal–Wallis test with Dunn’s multiple comparisons, or the Student’st-test or Wilcoxon’s rank-sum test with the Shapiro–Wilk normality test. The values of VZ were analysed using receiver operating characteristic (ROC) curve analysis to identify the optimal cut-off point to determine if this parameter predicted non-pregnancy.MAIN RESULTS AND THE ROLE OF CHANCESulfation and sialylation changes induced in the luminal epithelial glycocalyx decreased the value of VZ. VZ showed a significant daily decrease during the early stage of pregnancy (Day 1.5 versus 2.5 p.c.:P< 0.005; Student’st-test, Day 2.5 versus 3.5 p.c.:P< 0.001; Wilcoxon’s rank-sum test, Day 3.5 versus 4.5 p.c.:P< 0.005; Student’st-test, Day 4.5 versus 5.5 p.c.:P< 0.05; Student’st-test). One day before implantation began, VZ in the implantation failure model mice was significantly higher than in the control mice (P< 0.001, Wilcoxon’s rank-sum test). The ROC curve analysis of VZ as a predictor of non-conception showed areas under the ROC curve of 0.91 (95% CI: 0.83–0.99).LIMITATIONS, REASONS FOR CAUTIONAlthough it is influenced by surface charge in the uterine epithelium, the mechanism whereby VZ changes during early pregnancy is still unexplained.WIDER IMPLICATIONS OF THE FINDINGSLocal bioelectrical impedance may help to prospectively evaluate uterine receptivity in women. Including the measurement of local bioelectrical impedance as part of a frozen–thawed embryo transfer strategy may improve the efficiency of ART.STUDY FUNDING/COMPETING INTEREST(S)This work was supported in part by the …