Understanding Metabolic-Reproductive Disruption in Vertebrates: Lifelong Mitochondrial, Epigenomic and Physiological Effects of Developmental Exposure to Environmental Toxicants

Substantial evidence exists that early exposure to endocrine disruptors (EDs) causes reproductive dysfunction in vertebrates.

Some of the OECD guidelines for testing the effects of EDs address later-life effects on reproduction triggered by embryonic exposures.

However, in addition to reproductive effects, exposure to EDs during early life is reported to play a fundamental role in the onset of metabolic diseases, which are of high global concern.

Despite this, the OECD guidelines do not include tests to investigate later-life metabolic disruption triggered by early exposure to EDs.

Thus, there is an urgent need for the development of tools in vertebrates that effectively assess metabolic disruption after embryonic exposure to environmental contaminants (including EDs).

In this proposal, we will perform experiments in chickens that aim for a thorough assessment of metabolic and reproductive disruption induced by EDs during early development.

Taking advantage of the fact that avian eggs allow for tightly controlled embryonic exposures, chicken eggs will be exposed at critical developmental times to selected environmental contaminants (EDs).

We will then assess the metabolic consequences of early embryonic exposure to EDs before hatching (via egg respiration), as well as the long-term effects on mitochondrial function and epigenome, organismal physiology, and sperm nuclear epigenome. Finally, Adverse Outcome Pathways (AOPs) will be developed with the data obtained.