Journal
HUMAN REPRODUCTION UPDATE
Volume 20, Issue 1, Pages 63-75Publisher
OXFORD UNIV PRESS
DOI: 10.1093/humupd/dmt043
Keywords
development; fetal; programming; transgenerational; animal models
Categories
Funding
- University Department of Obstetrics and Gynaecology, University of Cambridge
- Academy of Medical Sciences (AMS) [AMS-SGCL11-AikenC] Funding Source: researchfish
- British Heart Foundation [FS/09/029/27902] Funding Source: researchfish
- Medical Research Council [MC_UU_12012/5/B, G0600717B, MC_UU_12012/4, G0600717] Funding Source: researchfish
- MRC [G0600717, MC_UU_12012/4] Funding Source: UKRI
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BACKGROUND: The concept of developmental programming suggests that the early life environment influences offspring characteristics in later life, including the propensity to develop diseases such as the metabolic syndrome. There is now growing evidence that the effects of developmental programming may also manifest in further generations without further suboptimal exposure. This review considers the evidence, primarily from rodent models, for effects persisting to subsequent generations, and evaluates the mechanisms by which developmental programming may be transmitted to further generations. In particular, we focus on the potential role of the intrauterine environment in contributing to a developmentally programmed phenotype in subsequent generations. METHODS: The literature was systematically searched at http://pubmed.org and http://scholar.google.com to identify published findings regarding transgenerational (F2 and beyond) developmental programming effects in human populations and animal models. RESULTS: Transmission of programming effects is often viewed as a form of epigenetic inheritance, either via the maternal or paternal line. Evidence exists for both germline and somatic inheritance of epigenetic modifications which may be responsible for phenotypic changes in further generations. However, there is increasing evidence for the role of both extra-genomic components of the zygote and the interaction of the developing conceptus with the intrauterine environment in propagating programming effects. CONCLUSIONS: The contribution of a suboptimal reproductive tract environment or maternal adaptations to pregnancy may be critical to inheritance of programming effects via the maternal line. As the effects of age exacerbate the programmed metabolic phenotype, advancing maternal age may increase the likelihood of developmental programming effects being transmitted to further generations. We suggest that developmental programming effects could be propagated through the maternal line de novo in generations beyond F2 as a consequence of development in a suboptimally developed intrauterine tract and not necessarily though directly transmitted epigenetic mechanisms.
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