Transcriptome changes affecting Hedgehog and cytokine signalling in the umbilical cord: implications for disease risk.
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.
Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore, Singapore. Walter_Stunkel@sics.a-star.edu.sg
Walter
W
Stünkel
Hong
H
Pan
Siew Boom
SB
Chew
Emilia
E
Tng
Jun Hao
JH
Tan
Li
L
Chen
Roy
R
Joseph
Clara Y
CY
Cheong
Mei-Lyn
ML
Ong
Yung Seng
YS
Lee
Yap-Seng
YS
Chong
Seang Mei
SM
Saw
Michael J
MJ
Meaney
Kenneth
K
Kwek
Allan M
AM
Sheppard
Peter D
PD
Gluckman
Joanna D
JD
Holbrook
D000328:Adult; D001724:Birth Weight; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D005006:Ethnicity; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D053823:Hedgehog Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D008297:Male; D046228:Microarray Analysis; D011247:Pregnancy; D047928:Premature Birth / Q000208:ethnology / Q000235:genetics*; D015398:Signal Transduction; D012846:Singapore; D059467:Transcriptome; D014470:Umbilical Cord / Q000737:chemistry*
D016207:Cytokines; D053823:Hedgehog Proteins