인문학
사회과학
자연과학
공학
의약학
농수해양학
예술체육학
복합학
DBpia AI
AI 에이전트
AI 아이디어
AI 리더
AI 뷰어
Citeasy
크롬 서지관리 다운로드
지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
초록·키워드
Background: Placental development occurs concurrently with fetal cardiogenesis and share many developmental pathways. Recent data from animal models suggest a link between placental inflammation and abnormal heart development, but no studies have elucidated the molecular processes connecting specific placental lesions to fetal congenital heart disease (CHD) in humans. Objective: To determine differentially expressed genes and affected biological processes in placental tissue from pregnancies complicated by fetal left ventricular outflow tract obstruction (LVOTO) as well as chronic inflammatory and vascular placental pathologies. Methods: Total RNAs were extracted from archived Formalin-Fixed Paraffin-Embedded (FFPE) placental tissues from pregnancies complicated by LVOTO (n=24) and healthy control pregnancies (n=10) using AllPrep DNA/RNA FFPE Kit (Qiagen, Hilden, Germany) according to the kit protocol. The RNAs were subjected to strand-specific whole transcriptome library preparation, and sequenced using NextSeq 500/550 v2.5 High Output Kit (paired end reads - 75 cycles) (Illumina, San Diego, CA). Gene read counts were log-scaled and quantile normalized to generate expression levels. To determine the molecular factors that influences chronic placental pathologies, we performed unpaired t-test and expression fold change (FC) were used to compare groupwise differential gene expression: placentas with LVOTO and no placental pathology (Group 1) to those with LVOTO and specific placental lesions [Group 2: fetal vascular malperfusion (FVM); Group 3: chronic villitis; Group 4: maternal vascular malperfusion (MVM)]. Gene set enrichment analyses (GSEA) were performed on ranked genes based on Log2[FC] to identify overlaps with common biological processes. Results: Group 1 showed 7143 genes that were differentially expressed (n=3859 genes upregulated; n=3284 genes downregulated) compared to healthy control [P <0.05]. Upregulated genes overlapped with circulatory and vascular development processes (False Discovery Rate [FDR] <0.0001). Downregulated genes overlapped with lipid biosynthesis and metabolic processes (FDR <0.002). There were 115 differentially expressed genes when compared between Group 2 (FVM) and Group 1 and GSEA analysis showed that downregulated genes overlapped with organ developmental processes (FDR<0.0005). Notably, GSEA analyses also showed that upregulated genes in chronic villitis (Group 3) overlapped with immune mediated processes, and downregulated genes in MVM overlapped with developmental and inflammatory response processes (FDR <0.05). Conclusion: Developmental and immune/inflammatory processes were most prominently represented in our transcriptomics data supporting a potential role for these biological processes in the chronic placental changes in pregnancies complicated by LVOTO. Validation of these results by expanding the cohort of patient FFPE tissues for additional gene expression analyses, and further establishing the mechanistic connections between these candidate genes, placental pathologies and specific forms of CHD are warranted. We acknowledge the following grants that funded this research: UT Southwestern Circle of Friends Synergy Grant (D.U and R.L.L), K23 HL161617-01A1 (R.L.L) and the AHA 23CDA1051500 (R.L.L).
인공지능 문자 인식 모델을 통해 추출된 텍스트로, 일부 오타나 오류가 포함될 수 있으나 지속적으로 개선 중입니다.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
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