Environmental conditions experienced in one generation can influence traits in future generations. In mammals, a father’s experiences can shape metabolism and other traits in offspring, and we and others have identified small RNAs in sperm as the likely carriers of paternal environmental information. Intriguingly, these small RNAs are first synthesized in a long tube known as the epididymis and then shipped to maturing sperm, raising the central question of how the epididymis senses the environment to modulate the RNAs delivered to sperm.
As a potential answer to this question, we have recently discovered that neurons may ship molecular information to the male reproductive tract, suggesting that interpretation of environmental conditions by the brain plays a role in programming the epigenetic payload of sperm. We propose in this project to investigate the connection between the central nervous system and the male reproductive tract. Deliverables include 1) a map of connections between different brain regions and the epididymis; 2) identification of the information carrier between the brain and epididymis; 3) a survey of how environmental conditions affect information trafficked by this pathway. This project will open the door to understanding how fathers interpret the environment to help guide their children's development and well-being. This will offer new insights into the web of connections between distant tissues in the body, and will significantly impact our understanding of the causes of complex diseases such as diabetes.