DNA methylation of stress-related genes and LINE-1 repetitive elements across the healthy human placenta

Non, A.L.; Binder, A.M.; Barault, L.; Rancourt, R.C.; Kubzansky, L.D.; Michels, K.B.

doi:10.1016/j.placenta.2011.12.013

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Volume 33, Issue 3 , Pages 183-187, March 2012

DNA methylation of stress-related genes and LINE-1 repetitive elements across the healthy human placenta

A.L. Non
- Robert Wood Johnson Health and Society Scholar, Harvard University, Cambridge, MA 02138, USA
- Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
- Department of Society, Human Development, and Health, Harvard School of Public Health, Boston, MA 02115, USA
- Corresponding author. Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, 221 Longwood Ave, BLI-350, Boston, MA 02115, USA. Tel.: +1 617 732 5106; fax: +1 617 732 4899.
A.M. Binder
- Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA
L. Barault
- Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
R.C. Rancourt
- Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA
- Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
L.D. Kubzansky
- Department of Society, Human Development, and Health, Harvard School of Public Health, Boston, MA 02115, USA
K.B. Michels
- Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA
- Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA

Accepted 16 December 2011. published online 06 January 2012.

Abstract

Objectives

DNA methylation is known to play a critical role in regulating development of placental morphology and physiology. The methylation of genes mediated by glucocorticoid hormones may be particularly vulnerable to intrauterine stress in the placenta. However little is known about DNA methylation of stress-related genes within a healthy placenta, and particularly whether methylation occurs uniformly across different regions of the placenta, which is a critical question for researchers seeking to analyze methylation patterns. We examined DNA methylation across four regions of the placenta to evaluate methylation levels of stress-related genes within a healthy placenta, and to evaluate whether methylation patterns vary by sampling location.

Study design

We evaluated levels of DNA methylation of three stress-related genes: NR3C1, BDNF, and 11B-HSD2 and of the repetitive element, LINE-1, in four different sample locations of 20 healthy placentas.

Main outcome measures

Pyrosequencing was used to quantify levels of methylation at CpG sites within the promoter regions of each of the three stress-related genes, and global methylation of LINE-1.

Results

Very low levels of methylation were found across all three stress-related genes; no gene showed a median methylation level greater than 4.20% across placental regions. Variation in methylation between placental regions for stress-related genes and for LINE-1 was minimal.

Conclusions

Our data suggest that these frequently studied stress-related genes have low levels of methylation in healthy placenta tissue. Minimal variation between sites suggests that sampling location does not affect DNA methylation analyses of these genes or of LINE-1 repetitive elements.

Keywords: Placenta, Glucocorticoid receptor, BDNF, 11B-HSD2, LINE-1, Stress