Amer J Perinatol
DOI: 10.1055/s-0037-1613682
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Epigenetic Regulation of the Nitric Oxide Pathway, 17-α Hydroxyprogesterone Caproate, and Recurrent Preterm Birth

Tracy A. Manuck1, Lisa Smeester2, Elizabeth M. Martin2, Martha S. Tomlinson2, Christina Smith1, Michael W. Varner3, 4, Rebecca C. Fry2
  • 1Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
  • 2Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
  • 3Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, Utah
  • 4Intermountain Healthcare Women and Newborns Clinical Program, Salt Lake City, Utah
Further Information

Publication History

03 November 2017

10 November 2017

Publication Date:
14 December 2017 (eFirst)

Abstract

Objective We sought to evaluate nitric oxide pathway placental gene expression and the epigenome (CpG methylation) among women receiving 17-α hydroxyprogesterone caproate (17-OHPC) with and without recurrent preterm birth (PTB).

Study Design This was a case–control study. We prospectively recruited women with ≥ 1 prior singleton spontaneous PTB <34 weeks receiving 17-OHPC. DNA and RNA were isolated from placentas. RNA abundance (gene expression) and the methylome were analyzed for 84 genes in nitric oxide pathways. Women with recurrent PTB <34 weeks (cases) were compared with those delivering at term (controls). Statistical analysis included multivariable models with Bonferroni's corrected p-values.

Results In this study, 17 women met inclusion criteria; 7 preterm cases (delivered at 22.6 ± 2.9 weeks) and 10 term controls (delivered at 38.5 ± 0.8 weeks). Groups had similar PTB history, race/ethnicity, and socioeconomic risk factors for PTB. Twenty-seven nitric oxide genes displayed differential expression (p < 0.05 and q < 0.10) when comparing placentas from preterm cases and term controls; all were downregulated in preterm cases. Eight hundred sixty corresponding CpG sites were differentially methylated between the preterm cases and term controls (Bonferroni's p-value <0.05).

Conclusion CpG methylation and gene expression patterns in nitric oxide pathway genes differ among placentas from recurrent PTB compared with term birth following 17-OHPC exposure.

Note

This study was presented in part at the Society for Maternal Fetal Medicine's 37th Annual Meeting (Las Vegas, NV), January 26, 2017, as a poster presentation, final abstract ID# 379.