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The amniotic fluid transcriptome: a source of novel information about human fetal development.

ABSTRACT: Amniotic fluid is a complex biological material that provides a unique window into the developing human. Residual amniotic fluid supernatant contains cell-free fetal RNA. The objective of this study was to develop an understanding of the amniotic fluid core transcriptome by analyzing the transcripts ubiquitously present in the amniotic fluid supernatant of euploid midtrimester fetuses.This was an in silico (computational) investigation using publicly available gene expression data previously produced by our group from 12 euploid midtrimester amniotic fluid samples. Functional analyses were performed using a web-based software analysis tool. Organ specificity was examined for each transcript using a gene expression atlas. For fetal organs not represented in the atlas, manual literature searching and the web-based software analysis tool were used to generate fetal organ-associated gene lists.There were 476 well-annotated genes present in 12 of 12 amniotic fluid samples. Functional analysis identified six physiologic systems represented in the amniotic fluid core transcriptome, including musculoskeletal and nervous system development and function and embryonic and organismal development. Mammalian target of rapamycin signaling was identified as a key canonical pathway. Twenty-three highly organ-specific transcripts were identified; six of these are known to be highly expressed in the fetal brain.Amniotic fluid cell-free fetal RNA can provide biological information on multiple fetal organ systems. The presence of fetal-brain specific transcripts in amniotic fluid suggests novel approaches to the study of developmental disorders that involve the central nervous system. The finding that the mammalian target of rapamycin signaling is enriched in midtrimester fetuses may have future applications in the study of fetal growth disorders.

SUBMITTER: Hui L

PROVIDER: S-EPMC3273331 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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The amniotic fluid transcriptome: a source of novel information about human fetal development.

Hui Lisa L Slonim Donna K DK Wick Heather C HC Johnson Kirby L KL Bianchi Diana W DW

Obstetrics and gynecology 20120101 1

<h4>Objective</h4>Amniotic fluid is a complex biological material that provides a unique window into the developing human. Residual amniotic fluid supernatant contains cell-free fetal RNA. The objective of this study was to develop an understanding of the amniotic fluid core transcriptome by analyzing the transcripts ubiquitously present in the amniotic fluid supernatant of euploid midtrimester fetuses.<h4>Methods</h4>This was an in silico (computational) investigation using publicly available g ...[more]

PMID: 22183218

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Project description:BackgroundThe amniotic fluid (AF) cell-free transcriptome is modulated by physiologic and pathologic processes during pregnancy. AF gene expression changes with advancing gestation reflect fetal development and organ maturation; yet, defining normal expression and splicing patterns for biomarker discovery in obstetrics requires larger heterogeneous cohorts, evaluation of potential confounding factors, and novel analytical approaches.MethodsWomen with a normal pregnancy who had an AF sample collected during midtrimester (n?=?30) or at term gestation (n?=?68) were included. Expression profiling at exon level resolution was performed using Human Transcriptome Arrays. Differential expression was based on moderated t-test adjusted p?<?0.05 and fold change >?1.25; for differential splicing, a splicing index >?2 and adjusted p?<?0.05 were required. Functional profiling was used to interpret differentially expressed or spliced genes. The expression of tissue-specific and cell-type specific signatures defined by single-cell genomics was quantified and correlated with covariates. In-silico validation studies were performed using publicly available datasets.Results1) 64,071 genes were detected in AF, with 11% of the coding and 6% of the non-coding genes being differentially expressed between midtrimester and term gestation. Expression changes were highly correlated with those previously reported (R?>?0.79, p?<?0.001) and featured increased expression of genes specific to the trachea, salivary glands, and lung and decreased expression of genes specific to the cardiac myocytes, uterus, and fetal liver, among others. 2) Single-cell RNA-seq signatures of the cytotrophoblast, Hofbauer cells, erythrocytes, monocytes, T and B cells, among others, showed complex patterns of modulation with gestation (adjusted p?<?0.05). 3) In 17% of the genes detected, we found differential splicing with advancing gestation in genes related to brain development processes and immunity pathways, including some that were missed based on differential expression analysis alone.ConclusionsThis represents the largest AF transcriptomics study in normal pregnancy, reporting for the first time that single-cell genomic signatures can be tracked in the AF and display complex patterns of expression during gestation. We also demonstrate a role for alternative splicing in tissue-identity acquisition, organ development, and immune processes. The results herein may have implications for the development of fetal testing to assess placental function and fetal organ maturity.

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The amniotic fluid transcriptome: a source of novel information about human fetal development.

Publications

The amniotic fluid transcriptome: a source of novel information about human fetal development.

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