Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - DAMAGE (An avian model for understanding and preventing the negative effects of poor developmental conditions on subsequent health state, fertility and ageing rate)

Teaser

The conditions experienced by embryos during development can vary drastically between individuals. Such variations in the quality of developmental conditions are suspected to have both short and long-term consequences for individual health, which could affect longevity. This...

Summary

The conditions experienced by embryos during development can vary drastically between individuals. Such variations in the quality of developmental conditions are suspected to have both short and long-term consequences for individual health, which could affect longevity. This is for instance exemplified in humans by the well known impact of low or high birth weight on subsequent health at adulthood (e.g. risks of cardiovascular disease or type II diabetes). Understanding the physiological processes underlying these deleterious effects of poor developmental conditions that influence health state later in life is a major challenge in biology, which requires the development of appropriate animal models. The aim of this project was to develop an avian model for understanding the negative effects of poor developmental conditions on subsequent health state, fertility and ageing rate, since mammalian models do not allow the manipulation of embryonic development without any concurrent alteration of the mother’s state. In addition, the telomere biology of birds appears to be closer to the telomere biology of human than classical short-lived laboratory rodent models, which is especially important considering the putative role of this ageing pathway in explaining the long-lasting consequences of adverse developmental conditions.
Overall, this Marie Curie Fellowship was a success in developing a new avian model to investigate the effects of poor developmental conditions on health state. Using this model, we were able to show that a variety of developmental stressors (i.e. accelerated or unstable development, but also low availability of resources) were associated with an accentuated shortening of telomeres, those protective structures of the genome that leads to cellular senescence when they reach a critically short length. These findings pave the way for testing potential preventive strategies in the future.

Work performed

During this fellowship, I conducted experimental work using Japanese quail, from eggs to adult birds. I optimized incubation conditions of eggs to be able to accelerate, decelerate or alter the stability of embryo development using variations in incubation temperature. I also used eggs coming from selection lines that have been selected for a low or a high maternal investment as measured by egg size, to test the importance of pre-natal resource availability.

I collected data on embryo development such as organ size and heart rate, and biological samples (blood, brain and heart) from a subsample of embryos. I found that developmental conditions have a profound impact on heart morphology and function, especially with slow development being associated with a slow heart rate and an increased heart size. I conducted biochemical and molecular analysis to measure markers related to the ageing process. Analysis of results is still ongoing, but it seems that telomere length is unaffected by developmental rate or stability, but is reduced in embryos having low resource availability during development (i.e. from small eggs). Developmental conditions also had an impact on mitochondrial function (the powerhouse of eukaryotic cells), since unstable developmental conditions were associated with more active mitochondria in the brain, and low resource availability was associated with impaired mitochondrial function in both the heart and the brain. Finally, unstable development was also associated with a rise in plasma stress hormones in embryos, suggesting a role of developmental stability in programming stress physiology prenatally.

I also collected data on birds postnatally, from hatching to adulthood, about their morphology, reproduction, behaviour and physiology. Overall, incubation temperature did not alter growth rate and adult morphology, but I found marked differences in behaviour and physiology. First, chicks developing under unstable conditions were less stressed and more explorative. Second, developmental conditions had no significant impact on reproductive traits measured as testis size for males and cumulative egg production (size and number) for females. Finally, developmental conditions had a clear-cut effect on telomere dynamics with age, with birds having shorter telomeres when developing fast, under less stable conditions or with less resource available. Therefore, poor conditions experienced during embryo development appear as a major determinant of telomere length, which could mediate the known long-term impact of poor early-life conditions on subsequent health.

The results of this project have been presented at several national and international conferences, including two symposia on the diversity of telomere dynamics organized in Edinburgh in 2016 and 2017, which were ideal opportunities to present my research to a broad range of scientists (from ecologists to epidemiologists) interested in telomeres and ageing. In addition, I finished this fellowship by presenting my research at the Society for Integrative and Comparative Biology Annual Meeting in San Francisco in January 2018, which enabled me to reach a broad audience across North America, and opened new perspectives for transatlantic collaborations.

Final results

By developing a new avian model of prenatal adversity, this fellowship yielded unprecedented data about the impact of early-life conditions on physiological processes conditioning health state later in life, such as telomere shortening, mitochondrial function and oxidative stress. Such findings pave the way to test potential preventive strategies in the future, for instance by using antioxidant supplementation either pre- or postnatally to prevent oxidative stress and limit telomere shortening resulting from adverse prenatal conditions. Such preventive strategies could therefore be applied to human health in the context of poor pregnancy conditions.
In addition, this project led to a discovery suggesting that unstable temperature during incubation could reduce stress levels and increase exploration during the growth phase, which could lead to applications in the poultry industry to improve animal welfare.

Website & more info

More info: https://www.researchgate.net/profile/Antoine_Stier.