A guide to designing germline-dependent epigenetic inheritance experiments in mammals.

Recent work has demonstrated that environmental factors experienced by parents can affect their offspring across multiple generations, and that such transgenerational transmission can depend on the germline. Causal evidence for the involvement of germ cells is rare, however, and the underlying molecular mechanisms remain poorly understood. Further, studies often employ varying methods in experimental design and data interpretation. We provide a critical analysis of these issues and suggest possible solutions and guidelines for improving study design and generating reproducible and high-quality data.