Altered DNA Methylation in Human Placenta after (Suspected) Preterm Labor

Abstract

Aim: The aim of this study was to determine if alterations in DNA methylation in the human placenta would support suspected preterm labor as a pathologic insult associated with diminished placental health. Methods: We evaluated placental DNA methylation at seven loci differentially methylated in placental pathologies using targeted bisulfite sequencing, in placentas associated with preterm labor (term birth after suspected preterm labor [n = 15] and preterm birth [n = 15]), and controls (n = 15). Results: DNA methylation levels at the NCAM1 and PLAGL1 loci in placentas associated with preterm labor did differ significantly (p < 0.05) from controls. Discussion: Specific alterations in methylation patterns indicative of an unfavourable placental environment are associated with preterm labor per se and not restricted to preterm birth.

Graphical abstract

Keywords::

• DNA methylation
• inflammation
• LOT1/PLAGL1
• placenta
• preterm birth
• suspected preterm labor

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-2019-0346

Acknowledgments

We acknowledge the use of Servicios Científico Técnicos del CIBA (IACS-Universidad de Zaragoza), specifically the ‘Secuenciación y Genómica Funcional’ unit. Special thanks goes to Montserrat Salas Valero (IACS) for reference management. We are grateful to Marta Ondarra (IACS) and Silvia Vazquez (FPCM) for their contributions to the experimental work and to Alberto Cebollada (IACS) for help with the statistics

Financial & competing interest disclosure

The work described in this manuscript has been financed by the Instituto Carlos III (Government of Spain) (PI10/301 and FIS PI17/02208). Our groups have been supported by several grants from the Government of Aragon, cofinanced by FEDER (‘Una manera de hacer Europa, Construyendo Europa desde Aragón’/European Social Funds): B77, B87 and B05_17D-2018. S Macias has been supported by PhD fellowship C071/2014 from the DGA (Aragón, Spain). D Oros was supported by the Instituto de Salud Carlos III (Government of Spain), through a mobility grant and intensification programme for researchers and Red de Salud Materno Infantil y del Desarrollo (SAMID), RETICS. Instituto de Salud Carlos III (ISCIII), Subdirección General de Evaluación y Fomento de la Investigación y Fondo Europeo de Desarrollo Regional (FEDER) Ref: RD12/0026. The funding sources had no involvement in the study design; collection, analysis and interpretation of data or in the writing of this report. R Ramos-Ruiz is the manager of the Genomics Unit of FPCM, which provides for fee scientific services to third parties. This activity has not influenced design and/or interpretation of the work described in this manuscript. 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.

Data sharing statement

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

The work described in this manuscript has been financed by the Instituto Carlos III (Government of Spain) (PI10/301 and FIS PI17/02208). Our groups have been supported by several grants from the Government of Aragon, cofinanced by FEDER (‘Una manera de hacer Europa, Construyendo Europa desde Aragón’/European Social Funds): B77, B87 and B05_17D-2018. S Macias has been supported by PhD fellowship C071/2014 from the DGA (Aragón, Spain). D Oros was supported by the Instituto de Salud Carlos III (Government of Spain), through a mobility grant and intensification programme for researchers and Red de Salud Materno Infantil y del Desarrollo (SAMID), RETICS. Instituto de Salud Carlos III (ISCIII), Subdirección General de Evaluación y Fomento de la Investigación y Fondo Europeo de Desarrollo Regional (FEDER) Ref: RD12/0026. The funding sources had no involvement in the study design; collection, analysis and interpretation of data or in the writing of this report. R Ramos-Ruiz is the manager of the Genomics Unit of FPCM, which provides for fee scientific services to third parties. This activity has not influenced design and/or interpretation of the work described in this manuscript. 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.