| Research Abstract |
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
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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
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