It is increasingly apparent that ancestral environmental conditions can affect phenotypes of future generations. In particular, a great deal of evidence indicates that parental exposure to stressors – ranging from social defeat to suboptimal diets to various environmental toxins – can all have significant effects on metabolism and behavior in children. In rodents, we and others have shown that paternal exposures can affect phenotypes in offspring, and there is some support for male germline effects in human epidemiological studies as well.
The mechanistic basis by which paternal experiences are transmitted to the next generation remains unclear. A burgeoning literature has documented a wide variety of exposure effects on the sperm epigenome, with diets, stress, and various toxins reported to alter sperm RNAs, DNA modifications, and genome packaging. Our ongoing research seeks to address the unanswered question of how paternal experiences control the molecular contents of sperm. Answering this question is essential if we hope to understand why some exposures impact offspring traits, while others do not. In other words, we seek to define the tissues responsible for “choosing” environmental conditions – presumably those with predictive value regarding future environments – about which to inform offspring.
Dietary and other exposures could impact the sperm epigenome via a wide range of mechanisms, from direct signaling in the developing germline through complex webs of inter- tissue signaling systems that link paternal sensing of environmental conditions to altered molecular contents of mature spermatozoa. I will discuss our latest efforts to develop systems for rigorous analysis of tissues responsible for controlling the sperm epigenome, and to explore signaling pathways in reproductive tissues that drive molecular changes in sperm in response to more naturalistic exposure paradigms.