Molecular analysis of twinning mechanism and its abnormality

孪晶机制及其异常的分子分析

• 批准号: 17591748
• 负责人: MASUZALI Hideaki
• 金额: $ 2.24万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591748/
• 关键词: twin-twin transfusion syndrome; acardiac twin; hPL mRNA; PSG; Syncytin; Placental mRNA; 多胎妊娠; cell-free mRNA; X不活性化; 遺伝子型解析; 予防; 分子マーカー; 定量的リアルタイムRT-PCR; 双胎妊娠; 卵生診断; 膜性診断; 表現型; 遺伝子型; 生殖補助医療; 後成的遺伝子修飾機序; X不活化

First of all, we investigated variable cases of monochorionic twin discordant for phenotypes between twins. For example, two cases of acardiac twin showed that acardius had skewed X-inactivation but normal co-twin had random pattern, suggesting that unequal division of embryo may be one of pathophysiologies of acardiac twin and also that molecular marker could assess a condition of unequal division of embryo. Therefore, our results above give a possibility that molecular marker is attractive tool to predict abnormal condition in twin. Consequently, we tried to identify the molecular marker for twin-twin transfusion syndrome (TTTS), which is one of severe conditions in cases of monochorionic twin. The purpose of the present study is to know whether cf-mRNA concentration in maternal plasma becomes a predictive marker of later TITS.Although all 17 cases of MCDA-T were not complicated by TTTS at the time of blood sampling, 5 cases subsequently developed TTTS (TTTS group), while the remaini … More ng 12 cases did not develop TTTS (no-TTTS group). Gestational ages at diagnosis of TITS were 15-25 weeks. And, 135 singleton pregnant women without medical complications at similar gestational age were also included as control group. Between the three groups, there were no significant differences in population characteristics, including the maternal age, the number of nulliparous women and the gestational age at the time of sampling (data not shown). The median (minimum-maximum) cf-PL mRNA MoM values were 1.80 (0.89-3.81) in the TTTS-group, 1.14 (1.77-1.35) in the no-TTTS group and 1.00 (0.82-2.05) in the control group, respectively. The cf-PL mRNA concentration was significantly higher in the TTTS group than in the no-TTTS group at adjusted gestational age (Mann-Whitney's U test, p=0.035), while there was no significant difference of cf-PL mRNA concentration between the no-TTTS group and the control group (p=0.41) (Figure 1). In addition, the median cf-GAPDH mRNA MoM value in the maternal plasma was significantly higher in the TTTS group (2.20; range, 1.30-2.68) than in the no-TTTS group (1.09; 0.68-3.25) (p=0.045). Our result suggested the possibility that inapparent pathophysiological changes had already occurred in the women who subsequently developed TTTS, though which specific conditions increased the levels of the maternal plasma mRNA in the TTTS group remain unknown.In conclusion, a quantitative aberration of both the cell-free PL and cell-free GAPDH mRNA in maternal circulation may be a novel predictive marker for TTTS, though both statistical differences were small and the sample size was too small to give sufficient strength to the analysis. Therefore, a combination of plural cell-free placental mRNA markers could be effective for the prediction of TTTS, similar to the situation for tumor markers. Further study to identify the gene transcripts, that are only expressed in the placenta, but not in blood cells, will hopefully not only help to both predict and prevent TTTS but may also help to further elucidate the pathophysiological condition of TTTS. Less

首先，我们研究了双胞胎之间表型不一致的单绒毛膜双胞胎的不同病例，例如，两例无心双胞胎显示，无心双胞胎具有偏向的X失活，但正常的同卵双胞胎具有随机模式，这表明胚胎的不均等分裂可能是由于。无心脏双胞胎的病理生理学之一，而且分子标记可以评估胚胎不均等分裂的情况，因此，我们的上述结果表明分子标记可能是预测双胞胎异常情况的有吸引力的工具。我们试图鉴定双胎输血综合征 (TTTS) 的分子标记，这是单绒毛膜双胞胎病例中测试的严重病症之一。本研究的目的是了解母体血浆中的 cf-mRNA 浓度是否会升高。尽管所有 17 例 MCDA-T 病例在采血时均未并发 TTTS，但其中 5 例随后出现 TTTS（TTTS 组），而其余 12 例未发生 TTTS（无 TTTS 组），诊断为 TITS 时的孕龄为 15-25 周，并且三组之间还纳入了 135 名无医学并发症的孕妇。人口特征没有显着差异，包括母亲年龄、未生育妇女人数和采样时的孕龄（数据未显示）cf-PL mRNA 中位数（最小-最大）。 TTTS组的MoM值分别为1.80（0.89-3.81），无TTTS组的MoM值为1.14（1.77-1.35），对照组的MoM值分别为1.00（0.82-2.05）。在调整胎龄时，TTTS 组显着高于无 TTTS 组（Mann-Whitney's U 检验， p=0.035），而 no-TTTS 组和对照组之间 cf-PL mRNA 浓度没有显着差异（p=0.41）（图 1）。 TTTS 组（2.20；范围，1.30-2.68）的母体血浆显着高于无 TTTS 组（1.09；范围，1.30-2.68）。 0.68-3.25) (p=0.045) 我们的结果表明，随后出现 TTTS 的女性可能已经发生了不明显的病理生理变化，但 TTTS 组中母体血浆 mRNA 水平增加的具体条件仍不清楚。结论是，母体循环中无细胞 PL 和无细胞 GAPDH mRNA 的定量异常可能是 TTTS 的新预测标志物，尽管两种统计差异都很小，而且样本量也很小。太小，无法为分析提供足够的强度，因此，多个无细胞胎盘 mRNA 标记的组合可以有效地预测 TTTS，类似于肿瘤标记的进一步研究，仅识别基因转录本。在胎盘中表达，但在血细胞中不表达，有望不仅有助于预测和预防 TTTS，还可能有助于进一步阐明 TTTS 的病理生理状况。

项目成果

一絨毛膜性双胎で認められる個体差の由来,ー膜性診断と卵性診断の重要性ー

在单绒毛膜双胞胎中观察到的个体差异的起源：膜性和排卵诊断的重要性

• 发表时间: 2005
• 期刊: 周産期医学 35
• 作者: Hirashima C;et al.;Takayama T.;Takayama T.;Matsubara S.;増崎英明
• 通讯作者: 増崎英明

Obstetrics clinical best practice (Advanced level) (Japanese)

产科临床最佳实践（高级）（日语）

• 发表时间: 2006
• 作者: Fujino;R.;Tanaka;K.et al.;Megumi Yanokura;Masuzaki H et al.
• 通讯作者: Masuzaki H et al.

Differential infiltration of macrophages and prostaglandin production by different uterine leiomyomas

• DOI: 10.1093/humrep/del205
• 发表时间: 2006-10-01
• 期刊: HUMAN REPRODUCTION
• 影响因子: 6.1
• 作者: Miura, Seiyou;Khan, Khaleque Newaz;Ishimaru, Tadayuki
• 通讯作者: Ishimaru, Tadayuki

Peritoneal fluid and serum levels of hepatocyte growth factor may predict the activity of endometriosis.

腹膜液和血清肝细胞生长因子水平可以预测子宫内膜异位症的活动性。

• 发表时间: 2006
• 期刊: Acta Obstet Gynecol Scand 85
• 作者: Khan KN;Masuzaki H;Fujishita A;Kitajima M;Hiraki K;Miura S;Sekine I;Ishimaru T
• 通讯作者: Ishimaru T

IUGRの原因

IUGR 的原因

• 发表时间: 2005
• 期刊: 産婦人科治療 90
• 作者: Hirashima C;et al.;Takayama T.;Takayama T.;Matsubara S.;増崎英明;S Yoshimura;KN Khan;吉村秀一郎;増崎英明;増崎英明;吉村秀一郎
• 通讯作者: 吉村秀一郎