On the Role of Seminal Fluid Protein and Nucleic Acid Content in Paternal Epigenetic Inheritance

The evidence supports the occurrence of environmentally-induced paternal epigenetic inheritance that shapes the offspring phenotype in the absence of direct or indirect paternal care and clearly demonstrates that sperm epigenetics is one of the major actors mediating these paternal effects. However, in most animals, while sperm makes up only a small portion of the seminal fluid, males also have a complex mixture of proteins, peptides, different types of small noncoding RNAs, and cell-free DNA fragments in their ejaculate. These seminal fluid contents (Sfcs) are in close contact with the reproductive cells, tissues, organs, and other molecules of both males and females during reproduction. Moreover, their production and use are adjusted in response to environmental conditions, making them potential markers of environmentally- and developmentally-induced paternal effects on the next generation(s). Although there is some intriguing evidence for Sfc-mediated paternal effects, the underlying molecular mechanisms remain poorly defined. In this review, the current evidence regarding the links between seminal fluid and environmental paternal effects and the potential pathways and mechanisms that seminal fluid may follow in mediating paternal epigenetic inheritance are discussed.