Pregnancy-Associated Changes in Cervical Noncoding RNA

Abstract

Aim: To identify pregnancy-associated changes in cervical noncoding RNA (ncRNA), including miRNA and long noncoding RNA (lncRNA), and their potential effects on biologic processes. Materials & methods: We enrolled 21 pregnant women with term deliveries (≥37 weeks’ gestation) in a prospective cohort and collected cervical swabs before 28 weeks’ gestation. We enrolled 21 nonpregnant controls. We analyzed miRNA, lncRNA and mRNA expression, applying a Bonferroni correction. Results: Five miRNA and three lncRNA were significantly differentially (>twofold change) expressed. Putative miRNA targets are enriched in genes mediating organogenesis, glucocorticoid signaling, cell adhesion and ncRNA machinery. Conclusion: Differential cervical ncRNA expression occurs in the setting of pregnancy. Gene ontology classification reveals biological pathways through which miRNA may play a biologic role in normal pregnancy physiology.

Keywords::

• cervix
• epigenetics
• gene ontology
• long noncoding RNA
• microRNA
• noncoding RNA
• pregnancy

Author contributions

The work reported in this manuscript was conducted at Beth Israel Deaconess Medical Center. Data analysis was performed at Beth Israel Deaconess Medical Center and at the University of Pennsylvania.

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2019-0231

Acknowledgments

We are thankful to M Ada, E Kennedy, E Nuss, A O’Neill and A Redhunt who have served as research assistants for the SPEC study. We acknowledge the staff who made this study possible at the Center for Maternal-Fetal Medicine, S Nippita and M Paul of Family Planning, the outpatient prenatal clinics and the Clinical Research Center at Beth Israel Deaconess Medical Center, as well as Bowdoin Street Health Center. We also are grateful to the SPEC study participants. miRNA array analysis was performed by the Genomics Core Facility, a part of the Health Sciences Cores at the University of Utah.

Financial & competing interests disclosure

Funding for this work came from the CH Hood Foundation. This work was also conducted with support from Harvard Catalyst – The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR001102), NIH/NIEHS K23ES02224204, P30ES000002, P30ES009089. Additional support came from the Chrissy and Jesse Brown Family. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved. This study was approved by the Institutional Review Board at Beth Israel Deaconess Medical Center (Protocol 2013P-000125).

Additional information

Funding

Funding for this work came from the CH Hood Foundation. This work was also conducted with support from Harvard Catalyst – The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR001102), NIH/NIEHS K23ES02224204, P30ES000002, P30ES009089. Additional support came from the Chrissy and Jesse Brown Family. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.