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

Abstract

The evidence in this study 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.

Inter- and transgenerational heritability of preconception chronic stress or alcohol exposure: Translational outcomes in brain and behavior

“…The authors concluded this discrepancy between naturally-sired and IVF offspring could be due to (1) differences in maternal care due to exposure to the PPS sire and (2) the fact that the IVF process could select sperm in different stages of the maturation process, and as a result, sperm with differential genomic imprinting ( Lee et al, 2002 ). However, seminal fluid can also confer epigenetic changes in offspring, ( Donkin et al, 2018 ; Patlar, 2022 ) meaning these results could point to a role of semen composition in the nongenomic inheritance of PPS. This is an intriguing mechanism that should be investigated with further studies of nongenomic stress-related phenotype transmission utilizing IVF.…”

Transgenerational Hangovers: A Rat Model for Behavioural and Epigenetic Changes Across Generations due to Paternal Preconceptual Alcohol Consumption

“…These findings suggest that DNA methylation may be the likely epigenetic mechanism involved in normal development. As mentioned in chapter 1, methylation can also be mediated by changes in seminal fluid proteins although, like the sncRNAs, the mechanisms here are unclear too (Patlar, 2022). Again, most DNA methylation in the sperm is also removed except for a few key loci which makes it the most likely means of epigenetic control.…”

“…As research focus has shifted away from gene mutations and towards epigenetics, there is also some recent evidence of the other components of sperm ejaculate playing a role. The seminal fluid which comprises a mixture of proteins, peptides, different types of small noncoding RNAs, and cell-free DNA fragments in the ejaculate appears to be involved in paternal epigenetic inheritance (Patlar, 2022). Seminal fluid compositions are highly influenced by the paternal environment such as diet, infection and exercise (Binder et al, 2015;Patlar et al, 2019;Ramm, 2020).…”

“…However, due to the novelty of the field, the mechanisms by which seminal fluids play a role are currently not well understood (Patlar, 2022). One of the suggested mechanisms for seminal fluids are that they mediate sperm epigenetics.…”

“…Again, there is some evidence showing chronic ethanol exposure alters several small non-coding RNAs (sncRNA) in the sperm (Bedi et al, 2019;Rompala et al, 2018). Lastly, the evidence of seminal fluids playing a mediating role in epigenetic changes and influencing development cannot be discounted (Patlar, 2022) These studies, while low in number, reinforce the impact of PPAC on offspring development and suggest changes in sperm which might impact offspring development. The other connecting question which remains is what are the driving molecular factors in the F0 fathers due to alcohol drinking which result in these sperm changes?…”