Repository logo
 

Molecular mechanisms governing offspring metabolic programming in rodent models of in utero stress.

Published version
Peer-reviewed

Change log

Authors

Christoforou, Efthimia R 
Sferruzzi-Perri, Amanda N  ORCID logo  https://orcid.org/0000-0002-4931-4233

Abstract

The results of different human epidemiological datasets provided the impetus to introduce the now commonly accepted theory coined as 'developmental programming', whereby the presence of a stressor during gestation predisposes the growing fetus to develop diseases, such as metabolic dysfunction in later postnatal life. However, in a clinical setting, human lifespan and inaccessibility to tissue for analysis are major limitations to study the molecular mechanisms governing developmental programming. Subsequently, studies using animal models have proved indispensable to the identification of key molecular pathways and epigenetic mechanisms that are dysregulated in metabolic organs of the fetus and adult programmed due to an adverse gestational environment. Rodents such as mice and rats are the most used experimental animals in the study of developmental programming. This review summarises the molecular pathways and epigenetic mechanisms influencing alterations in metabolic tissues of rodent offspring exposed to in utero stress and subsequently programmed for metabolic dysfunction. By comparing molecular mechanisms in a variety of rodent models of in utero stress, we hope to summarise common themes and pathways governing later metabolic dysfunction in the offspring whilst identifying reasons for incongruencies between models so to inform future work. With the continued use and refinement of such models of developmental programming, the scientific community may gain the knowledge required for the targeted treatment of metabolic diseases that have intrauterine origins.

Description

Keywords

Animal models, DOHAD, Development, Fetal, Metabolism, Programming, Animals, Disease Models, Animal, Epigenesis, Genetic, Insulin, Liver, Metabolism, Rodentia, Stress, Physiological

Journal Title

Cell Mol Life Sci

Conference Name

Journal ISSN

1420-682X
1420-9071

Volume Title

77

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MR/R022690/1)