Dataset Information

Transcriptome changes affecting Hedgehog and cytokine signalling in the umbilical cord: implications for disease risk.

ABSTRACT:

Background

Babies born at lower gestational ages or smaller birthweights have a greater risk of poorer health in later life. Both the causes of these sub-optimal birth outcomes and the mechanism by which the effects are transmitted over decades are the subject of extensive study. We investigated whether a transcriptomic signature of either birthweight or gestational age could be detected in umbilical cord RNA.

Methods

The gene expression patterns of 32 umbilical cords from Singaporean babies of Chinese ethnicity across a range of birthweights (1698-4151 g) and gestational ages (35-41 weeks) were determined. We confirmed the differential expression pattern by gestational age for 12 genes in a series of 127 umbilical cords of Chinese, Malay and Indian ethnicity.

Results

We found that the transcriptome is substantially influenced by gestational age; but less so by birthweight. We show that some of the expression changes dependent on gestational age are enriched in signal transduction pathways, such as Hedgehog and in genes with roles in cytokine signalling and angiogenesis. We show that some of the gene expression changes we report are reflected in the epigenome.

Conclusions

We studied the umbilical cord which is peripheral to disease susceptible tissues. The results suggest that soma-wide transcriptome changes, preserved at the epigenetic level, may be a mechanism whereby birth outcomes are linked to the risk of adult metabolic and arthritic disease and suggest that greater attention be given to the association between premature birth and later disease risk.

SUBMITTER: Stunkel W

PROVIDER: S-EPMC3393728 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Transcriptome changes affecting Hedgehog and cytokine signalling in the umbilical cord: implications for disease risk.

Stünkel Walter W Pan Hong H Chew Siew Boom SB Tng Emilia E Tan Jun Hao JH Chen Li L Joseph Roy R Cheong Clara Y CY Ong Mei-Lyn ML Lee Yung Seng YS Chong Yap-Seng YS Saw Seang Mei SM Meaney Michael J MJ Kwek Kenneth K Sheppard Allan M AM Gluckman Peter D PD Holbrook Joanna D JD

PloS one 20120710 7

<h4>Background</h4>Babies born at lower gestational ages or smaller birthweights have a greater risk of poorer health in later life. Both the causes of these sub-optimal birth outcomes and the mechanism by which the effects are transmitted over decades are the subject of extensive study. We investigated whether a transcriptomic signature of either birthweight or gestational age could be detected in umbilical cord RNA.<h4>Methods</h4>The gene expression patterns of 32 umbilical cords from Singapo ...[more]

PMID: 22808055

Similar Datasets

Project description:BACKGROUND: Babies born at lower gestational ages or smaller birthweights have a greater risk of poorer health in later life. Both the causes of these sub-optimal birth outcomes and the mechanism by which the effects are transmitted over decades are the subject of extensive study. We investigated whether a transcriptomic signature of either birthweight or gestational age could be detected in umbilical cord RNA. METHODS: The gene expression patterns of 32 umbilical cords from Singaporean babies of Chinese ethnicity across a range of birthweights (BW, 1698-4151g) and gestational ages (GA, 35-41 weeks) were determined. We confirmed the differential expression pattern by gestational age for 12 genes in a series of 127 umbilical cords of Chinese, Malay and Indian ethnicity. RESULTS: We found that the transcriptome is substantially influenced by gestational age; but less so by birthweight. We show that some of the expression changes dependent on gestational age are enriched in signal transduction pathways, such as Hedgehog and in genes with roles in cytokine signalling and angiogenesis. We show that some of the gene expression changes we report are reflected in the epigenome. CONCLUSIONS: We studied the umbilical cord which is peripheral to disease susceptible tissues. The results suggest that soma-wide transcriptome changes, preserved at the epigenetic level, may be a mechanism whereby birth outcomes are linked to the risk of adult metabolic and arthritic disease and suggest that greater attention be given to the association between premature birth and later disease risk. 8 umbilical cords form low birth weight babies, 8 umbilical cords from high birth weight babies, 14 umbilical cords from normal birth weigth babies, 7 matching the gestational ages of the low birth weigth group (norm1) and 7 matching the getsational ages of the high birth weight group (norm2). Replicates for array, cRNA and slide spotting REPLICATES: biological replicate: LBW_1, LBW_2, LBW_3A, LBW_3B, LBW_3C, LBW_4, LBW_5, LBW_6, LBW_7, LBW_8A, LBW_8B biological replicate: HBW_1, HBW_2A, HBW_2B, HBW_2C, HBW3, HBW4, HBW5, HBW6, HBW7, HBW8 biological replicate: norm1_1, norm1_2, norm1_3, norm1_4, norm1_5, norm1_7A, norm1_7B, norm1_7C, norm1_7D biological replicate: norm2_1, norm2_2, norm2_3, norm2_4, norm2_5, norm2_6A, norm2_6B, norm2_7 technical replicate: HBW_2A, HBW_2B, HBW_2C technical replicate: LBW_3A, LBW_3B, LBW_3C technical replicate: LBW_8A, LBW_8B techical replicate: norm1_7A, norm1_7B, norm1_7C, norm1_7D technical repliacte: norm2_6A, norm2_6B

Project description:ObjectivesTo determine risk factors for short and long umbilical cord, entanglement and knot. Explore their associated risks of adverse maternal and perinatal outcome, including risk of recurrence in a subsequent pregnancy. To provide population based gestational age and sex and parity specific reference ranges for cord length.DesignPopulation based registry study.SettingMedical Birth Registry of Norway 1999-2013.PopulationAll singleton births (gestational age>22weeks<45 weeks) (n = 856 300).MethodsDescriptive statistics and odds ratios of risk factors for extreme cord length and adverse outcomes based on logistic regression adjusted for confounders.Main outcome measuresShort or long cord (<10th or >90th percentile), cord knot and entanglement, adverse pregnancy outcomes including perinatal and intrauterine death.ResultsIncreasing parity, maternal height and body mass index, and diabetes were associated with increased risk of a long cord. Large placental and birth weight, and fetal male sex were factors for a long cord, which again was associated with a doubled risk of intrauterine and perinatal death, and increased risk of adverse neonatal outcome. Anomalous cord insertion, female sex, and a small placenta were associated with a short cord, which was associated with increased risk of fetal malformations, placental complications, caesarean delivery, non-cephalic presentation, perinatal and intrauterine death. At term, cord knot was associated with a quadrupled risk of perinatal death. The combination of a cord knot and entanglement had a more than additive effect to the association to perinatal death. There was a more than doubled risk of recurrence of a long or short cord, knot and entanglement in a subsequent pregnancy of the same woman.ConclusionCord length is influenced both by maternal and fetal factors, and there is increased risk of recurrence. Extreme cord length, entanglement and cord knot are associated with increased risk of adverse outcomes including perinatal death. We provide population based reference ranges for umbilical cord length.

Dataset Information

Transcriptome changes affecting Hedgehog and cytokine signalling in the umbilical cord: implications for disease risk.

Background

Methods

Results

Conclusions

Publications

Transcriptome changes affecting Hedgehog and cytokine signalling in the umbilical cord: implications for disease risk.

Similar Datasets

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