Preterm birth buccal cell epigenetic biomarkers to facilitate preventative medicine

Paul Winchester,Daniel Beck,Eric Nilsson,Michael K. Skinner

doi:10.1038/s41598-022-07262-9

Abstract

Preterm birth is the major cause of newborn and infant mortality affecting nearly one in every ten live births. The current study was designed to develop an epigenetic biomarker for susceptibility of preterm birth using buccal cells from the mother, father, and child (triads). An epigenome-wide association study (EWAS) was used to identify differential DNA methylation regions (DMRs) using a comparison of control term birth versus preterm birth triads. Epigenetic DMR associations with preterm birth were identified for both the mother and father that were distinct and suggest potential epigenetic contributions from both parents. The mother (165 DMRs) and female child (136 DMRs) at p < 1e−04 had the highest number of DMRs and were highly similar suggesting potential epigenetic inheritance of the epimutations. The male child had negligible DMR associations. The DMR associated genes for each group involve previously identified preterm birth associated genes. Observations identify a potential paternal germline contribution for preterm birth and identify the potential epigenetic inheritance of preterm birth susceptibility for the female child later in life. Although expanded clinical trials and preconception trials are required to optimize the potential epigenetic biomarkers, such epigenetic biomarkers may allow preventative medicine strategies to reduce the incidence of preterm birth.

Highlights

A number of potential biomarkers for preterm birth have been identified
One study found DNA methylation differences in umbilical cord tissue between preterm and full-term children[39]. These results indicate that DNA methylation changes may occur with preterm birth and suggest that DNA methylation changes are worth investigating as a viable biomarker for predicting preterm birth
The current study demonstrates that epigenetic biomarkers in maternal and paternal buccal cells may be useful, larger studies are needed for predicting preterm birth

Summary

Introduction

A number of potential biomarkers for preterm birth have been identified. Maternal serum levels of alphafetoprotein (ms-AFP) and human chorionic gonadotropin (ms-hCG) have been used clinically[6–8]. DNA methylation changes can be detected in obtained surrogate samples (i.e., marker cells not directly associated with the etiology of the pathology), such as cheek buccal epithelial c ells[34] This is due to the fact that epigenetic differences can be heritable, so all somatic cells derived from the embryo of an individual have cellspecific epigenetic changes derived from the g ermline[33]. Sperm epigenetic biomarkers reflect epigenetic inheritance of disease in offspring and subsequent generations, a surrogate cell such as buccal cells can reflect early embryo impacts on all somatic cells to be used for disease a ssessment[46,47] Together, these studies indicate that epigenetic biomarkers of preterm birth susceptibility or pathology potentially exist and are worthy of further development. The generational study presented suggests potential epigenetic inheritance aspects for preterm birth

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