Elucidation of the mechanism of miscarriage due to disruption of the pregnancy maintenance mechanism in fetal morphological abnormalities and its application to preimplantation diagnosis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09499
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Nagoya City University
• Principal Investigator: Suzumori Nobuhiro 名古屋市立大学, 医薬学総合研究院(医学), 准教授 (70326148)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 流産 / 胎生期形態異常 / エクソーム解析 / 胎児染色体 / 胎盤 / トリオ分析

Outline of Final Research Achievements

To elucidate the cause of miscarriage and stillbirth, fetal morphology and chromosomes were analyzed, and trio analysis of the couple and fetus was performed at the time of miscarriage in cases of two or more repeated miscarriage or stillbirth. Genomic DNA was extracted from peripheral blood and/or saliva, whole exome analysis was performed, DNA quantification was confirmed, the libraries were prepared, the exon region capture was performed, and sequencing was performed on NovaSeq6000 for normal karyotype in 16 of the 21 families with unexplained miscarriage cases.
Data were mapped with a whole exome analysis program, analyzed for the homozygous mutations and pathological variants, and searched in databases and PubMed. The elucidation of pathological variants related to miscarriage and stillbirth is difficult at this time, but we are continuing to carry out this study.

Free Research Field

産科婦人科学

Academic Significance and Societal Importance of the Research Achievements

流産・死産の原因検索のため、不育症の16家系、48検体全てを用いて全エクソーム解析によるトリオ分析を行い、ホモ接合体変異や複合ヘテロ接合体変異、病的バリアントの有無を解析したところ、明らかな病的バリアントを絞り込むことができなかったことから、不育症の遺伝学的解析により流産・死産の原因を単一の遺伝子多型の分析により解明することは困難であると思われる。一方、不育症に悩むカップルが多いなかで、その原因は胎児染色体異常、子宮形態異常、抗リン脂質抗体症候群以外にも多岐にわたり、胚・子宮内膜の局所での病理病態について未知の領域が多いと考えられる。