Adverse Intrauterine Environment and Cardiac miRNA Expression

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.

Epigenetic responses and the developmental origins of health and disease

“…Studies from several other laboratories have also demonstrated that miRNAs are associated with developmental programming of various organs (Zucchi et al 2013, Casas-Agustench et al 2015. The organs and tissues investigated include heart (Yan & Jiao 2016, Lock et al 2017), brain (Petri et al 2014) and several endocrine glands (pancreas, ovary, testes, hypothalamus and pituitary) (Kredo-Russo et al 2012, Voglova et al 2016. Of note, exposure to environmental toxins during human pregnancy affects miRNA expression in cord blood, which lead to increased disease susceptibility in offspring (Rager et al 2014, Gillet et al 2016).…”

Postnatal cardiovascular adaptation

“…This is, however, unlikely to mirror the advantages seen in pulmonary development. Intrauterine growth restriction has been extensively studied and undernutrition can result in maturational changes in the cardiac myocytes,62 this does not however translate into a clinical functional advantage 63. Furthermore, premature maturation may diminish the total myocyte count into adult life 44.…”

The role of miRNA regulation in fetal cardiomyocytes, cardiac maturation and the risk of heart disease in adults

“…2011). Premature exit from the cell cycle in fetal development can be caused by adverse changes to the intrauterine environment, resulting in a less structurally complete and less functional organ at birth and throughout postnatal life (Lock et al . 2017).…”

“…The expression of non‐coding RNAs, such as miRNAs, plays an important role in the epigenetic machinery and is vital for normal tissue development and function (Lock et al . 2017).…”

“…2017). miRNA expression acts to repress gene expression by interfering with target gene mRNA translation or stability (Lock et al . 2017).…”