(5)双胎形成のメカニズムとその異常に関する分子遺伝学的検討(講演要旨,<特集>第59回シンポジウム2「多胎妊娠の予防と管理」)

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Monochorionic dizygotic twins (MCDZ-T) and twin-twin transfusion syndrome (TTTS) were selected as target disease to get new knowledge leading to prevention and management of multiple pregnancy in assisted reproductive technology (ART) and perinatal medicine, respectively. Six pairs of MCDZ-T have been reported in a recent short period, though such twins are extremely rare in natural pregnancy. All the 6 cases of MCDZ-T were the products of pregnancy by ART. In this overview, we summarized these 6 cases, and discussed about possible mechanisms of this twinning and clinical implications of confined blood cell chimerism (CBC). MCDZ-T could be a risk factor for TTTS and the other complications in monochorionic twins. CBC, which is attributable to placental vessel anastomosis between DZT, may mislead physicians at occasion of blood transfusion and genotyping for a disease susceptibility test. Therefore, sufficient informed consent prior to ART and genetic counseling before/after birth are absolutely necessary for their better quality-of-life. TTTS, which is a serious complication in monochorionic twins, involves an unequal blood flow via the placental vascular anastomoses from the donor to the recipient twin. Although the placental anastomoses are present in all monochorionic twins and both fetuses are genetically identical, TTTS occurs in only 10〜15% of monochorionic twins and much of the pathophysiological basis of TTTS remains poorly understood. Clinically, a staging system based on the ultrasound features of TTTS is widely used for its management, but not for the prediction of TTTS. Also, the known predictive findings by ultra-sonographic examination are only detectable in a small portion of TTTS cases. New predictive markers are therefore desirable for the early detection and prevention of TTTS. Recently, cell-free placental mRNA (cfp-mRNA) became detectable in maternal plasma, and concentration of each marker is measur-able by mean of quantitative real-time RT-PCR. Thus, cfp-mRNA in maternal plasma has become an at-tractive target for the non-invasive monitoring of pregnancy disorders. In this study, microarray-based screening of genes, which are only expressed in the placenta, but not in blood cells, was performed and 6 cfp-mRNAs including hPL, PSG2, PSG3, Syncytin, Syncytin-2 and ADAM12 were isolated as the predic-tive molecular marker for later TTTS. In conclusion, multiple pregnancy associated with ART should be prevented, because its risk includes not only premature labor but also serious problems by chimerism and/or TTTS. Regarding a manage-ment of TTTS in perinatal medicine, a quantitative analysis of cfp-mRNAs will hopefully help to both predict and prevent TTTS in monochorionic twins.
2007-10-01

(5)双胎形成のメカニズムとその異常に関する分子遺伝学的検討(講演要旨,<特集>第59回シンポジウム2「多胎妊娠の予防と管理」)

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