Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 367, Issue 1-2, Pages 64-73Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2012.12.018
Keywords
Pre-eclampsia; Leptin; Placenta; DNA methylation
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Funding
- Child and Family Research Institute (CFRI)
- Canadian Institutes of Health Research [49520]
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In pre-eclampsia, placental leptin is up-regulated and leptin is elevated in maternal plasma. To investigate potential epigenetic regulation of the leptin (LEP) gene in normal and complicated pregnancy, DNA methylation was assessed at multiple reported regulatory regions in placentae from control pregnancies (n = 111), and those complicated by early onset pre-eclampsia (EOPET; arising <34 weeks; n = 19), late onset pre-eclampsia (LOPET; arising >= 34 weeks; n = 18) and normotensive intrauterine growth restriction (nIUGR; n = 13). The LEP promoter was hypomethylated in EOPET, but not LOPET or nIUGR placentae, particularly at CpG sites downstream of the transcription start site (-10.1%; P < 0.0001). Maternal plasma leptin was elevated in EOPET and LOPET (P < 0.05), but not nIUGR, compared with controls. EOPET cases showed a trend towards biallelic LEP expression rather than skewed allelic expression observed in control placentae, suggesting that loss of normal monoallelic expression at the LEP locus is associated with hypomethylation, leading to increased overall LEP expression. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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