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30 October 2017 Transcriptome-wide analysis suggests that temporal changes in the relative contributions of hyperplasia, hypertrophy and apoptosis underlie liver growth in pregnant mice
Leonie R. Price, Karen A. Lillycrop, Nicola A. Irvine, Mark A. Hanson, Graham C. Burdge
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Abstract

Maternal liver undergoes structural and metabolic changes during pregnancy to meet the demands of the developing fetus. In rodents, this involves increased liver weight, but the mechanism remains unclear. To address this, we analyzed the histology, gene expression, and DNA methylation of livers of nonpregnant and pregnant C57/BL6 mice. Gestational liver growth in pregnant mice was accompanied by increased hepatocyte area and lower cell density (days 14 and 18). Expression of cell proliferation markers was increased on days 14 and 18. A total of 115 genes were differentially expressed on day 14 and 123 genes on day 18 (79 on both days). Pathway analysis indicated that pregnancy involves progressive increase in cell proliferation and decreased apoptosis. This was confirmed using archived data from the FVB wild-type mouse liver transcriptome. Four differentially DNA methylated and two differentially DNA hydroxymethylated regions identified on days 14 and 18 by methylome-wide analysis, but were not associated with altered gene expression. Long interspersed nuclear element-1 hypomethylation on days 14 and 18 was accompanied by increased ten-eleven translocase-2 and decreased DNA methyltransferase 3a and 3b expression. These findings suggest that gestational liver growth involves increased mitosis and hypertrophy, and decreased apoptosis contingent on pregnancy stage. Such changes may involve repetitive sequence, but not gene specific, DNA methylation.

Summary Sentence

Gestational liver growth involves hyperplasia, hypertrophy, and apoptosis which differ in contribution with progressing pregnancy.

© The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Leonie R. Price, Karen A. Lillycrop, Nicola A. Irvine, Mark A. Hanson, and Graham C. Burdge "Transcriptome-wide analysis suggests that temporal changes in the relative contributions of hyperplasia, hypertrophy and apoptosis underlie liver growth in pregnant mice," Biology of Reproduction 97(5), 762-771, (30 October 2017). https://doi.org/10.1093/biolre/iox136
Received: 28 June 2017; Accepted: 27 October 2017; Published: 30 October 2017
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KEYWORDS
bisulfite sequencing
DNA methylation
hydroxyl DNA methylation
microarray
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