A Role for microRNAs in the Epigenetic Control of Sexually Dimorphic Gene Expression in the Human Placenta

Abstract

Aim: The contribution of miRNAs as epigenetic regulators of sexually dimorphic gene expression in the placenta is unknown. Materials & methods: 382 placentas from the extremely low gestational age newborns (ELGAN) cohort were evaluated for expression levels of 37,268 mRNAs and 2,102 miRNAs using genome-wide RNA-sequencing. Differential expression analysis was used to identify differences in the expression based on the sex of the fetus. Results: Sexually dimorphic expression was observed for 128 mRNAs and 59 miRNAs. A set of 25 miRNA master regulators was identified that likely contribute to the sexual dimorphic mRNA expression. Conclusion: These data highlight sex-dependent miRNA and mRNA patterning in the placenta and provide insight into a potential mechanism for observed sex differences in outcomes.

Keywords::

• epigenetics
• epigenome
• miRNA
• mRNA
• placenta
• sexual dimorphism

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-2020-0062

Financial & competing interests disclosure

This study was supported by grants from the National Institute of Neurological Disorders and Stroke (U01NS040069; R01NS040069), the Office of the NIH Director (UG3OD023348, UH3OD023348), the National Institute of Child Health and Human Development (R01HD092374), and the National Institute of Nursing Research (K23NR017898). 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 study was approved by the Institutional Review Board at each of the 14 participating ELGAN sites and informed consent has been obtained from the participants involved. 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

Sequencing data have been submitted to National Center for Biotechnology Information (NCBI) Gene Expression Omnibus repository.

Additional information

Funding

This study was supported by grants from the National Institute of Neurological Disorders and Stroke (U01NS040069; R01NS040069), the Office of the NIH Director (UG3OD023348, UH3OD023348), the National Institute of Child Health and Human Development (R01HD092374), and the National Institute of Nursing Research (K23NR017898). 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.