Maternal womb conditions impact health.

Accumulating evidence suggests that early events at the time around conception and implantation are of utmost importance for embryo development and subsequent health and lifespan. Besides maternal diabetes and obesity, assisted reproductive technologies (ARTs) have also been associated with genetic alterations and perturbations in genomic imprinting.

Investigators in the EU-funded EPIHEALTH (Linking perturbed maternal environment during periconceptional development, due to diabetes, obesity or assisted reproductive technologies, and altered health during ageing) project are studying the influence of the maternal environment with respect to metabolic state on the development of the foetus.

The researchers have evaluated human microarray databases derived from the blastocyst stage for differential expression of important developmental genes as well as signalling pathways critical in developmental programming.

Bioinformatics analysis of data sets on patients borne from diabetic mothers or from ARTs was performed to predict the importance of these pathways in health and lifespan.

Studies on diabetic rabbits revealed that blastocyst-stage embryos suffer from diabetes-like metabolic changes and altered insulin signalling that causes delayed development. At the very early stages of development, foetuses showed protein modifications. Preliminary observations from mouse models of ARTs suggest that advanced oocyte age influences foetal development and such offspring tend to grow faster.

A considerable part of EPIHEALTH research is devoted to the Krüppel associated box (KRAB) zinc finger proteins, a family of transcriptional repressors. In particular, their role in early developmental epigenetic events is being investigated, including a novel project-developed genome-wide mapping of KRAB zinc finger binding sites. This will be used to compare their findings to the methylation analysis data from individuals of a wide age range – 20 to 104 years.

Many long-lived individuals (LLIs) more than 90 years of age show an absence or a delayed onset of age-related diseases. EPIHEALTH researchers have established a blood bank for LLIs to compare the epigenetic profiles of such individuals.

The EPIHEALTH consortium stands to provide unprecedented information on the role of the maternal environment during embryonic development and human biological variations in health and disease. These findings could be used to improve the health of future generations and prolong human lifespan