Adverse Intrauterine Environment and Cardiac miRNA Expression.

Mitchell Lock,Kimberley Botting,Janna Morrison,Doug Brooks,Ross Tellam

doi:10.3390/ijms18122628

Abstract

Placental insufficiency, high altitude pregnancies, maternal obesity/diabetes, maternal undernutrition and stress can result in a poor setting for growth of the developing fetus. These adverse intrauterine environments result in physiological changes to the developing heart that impact how the heart will function in postnatal life. The intrauterine environment plays a key role in the complex interplay between genes and the epigenetic mechanisms that regulate their expression. In this review we describe how an adverse intrauterine environment can influence the expression of miRNAs (a sub-set of non-coding RNAs) and how these changes may impact heart development. Potential consequences of altered miRNA expression in the fetal heart include; Hypoxia inducible factor (HIF) activation, dysregulation of angiogenesis, mitochondrial abnormalities and altered glucose and fatty acid transport/metabolism. It is important to understand how miRNAs are altered in these adverse environments to identify key pathways that can be targeted using miRNA mimics or inhibitors to condition an improved developmental response.

Highlights

Cardiovascular and metabolic disorders often present in adult life, but may have their origins in changes to the intrauterine environment during fetal development [1,2]
Given that the number of cardiomyocytes a human will have for life is set at birth, it is important to understand how cardiomyocyte endowment is regulated in the developing fetus
We highlight a number of changes to the maternal and intrauterine environment and how these may impact on the expression of fetal cardiac miRNAs during development

Summary

Introduction

Cardiovascular and metabolic disorders often present in adult life, but may have their origins in changes to the intrauterine environment during fetal development [1,2]. We highlight a number of changes to the maternal and intrauterine environment and how these may impact on the expression of fetal cardiac miRNAs during development. Dicer1 deletion demonstrates the integral role of miRNAs in the regulation of cardiac development as well as postnatal maintenance of heart function.

Results

Conclusion