Tracy A Manuck1, Lisa Smeester2, Elizabeth M Martin2, Martha S Tomlinson2, Christina Smith1, Michael W Varner3,4, Rebecca C Fry2. 1. Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. 2. Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. 3. Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, Utah. 4. Intermountain Healthcare Women and Newborns Clinical Program, Salt Lake City, Utah.
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. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
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. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Authors: Paul A Harris; Robert Taylor; Robert Thielke; Jonathon Payne; Nathaniel Gonzalez; Jose G Conde Journal: J Biomed Inform Date: 2008-09-30 Impact factor: 6.317
Authors: Tracy A Manuck; Gregory J Stoddard; Rebecca C Fry; M Sean Esplin; Michael W Varner Journal: Am J Obstet Gynecol Date: 2016-07-11 Impact factor: 8.661
Authors: Yasushi Hirota; Nuray Acar; Susanne Tranguch; Kristin E Burnum; Huirong Xie; Ako Kodama; Yutaka Osuga; Ismail Ustunel; David B Friedman; Richard M Caprioli; Takiko Daikoku; Sudhansu K Dey Journal: Proc Natl Acad Sci U S A Date: 2010-08-16 Impact factor: 11.205
Authors: Tracy A Manuck; W Scott Watkins; Barry Moore; M Sean Esplin; Michael W Varner; G Marc Jackson; Mark Yandell; Lynn Jorde Journal: Am J Obstet Gynecol Date: 2014-03-01 Impact factor: 8.661
Authors: Tracy A Manuck; Lauren A Eaves; Julia E Rager; Karen Sheffield-Abdullah; Rebecca C Fry Journal: Epigenetics Date: 2021-07-24 Impact factor: 4.861