Paternal transgenerational epigenetic mechanisms mediating stress phenotypes of offspring

Abstract

Depression and anxiety risk are highly influenced by both genetic and environmental factors. Recently, it has been proposed that epigenetic mechanisms may also contribute to the transmission of both depression- and anxiety-related behaviors across multiple generations. This review highlights long-lasting epigenetic alterations observed in offspring of fathers, including some distinct effects on male and female offspring, in animal models. Available evidence emphasizes how both the developmental time point and the type of paternal stress (social vs. asocial) influence the complex transmission patterns of these phenotypes to future generations. This research is critical in understanding the factors that influence risk for depression and anxiety disorders and has the potential to contribute to the development of innovative treatments that can more precisely target vulnerable populations.

Keywords: epigenetics; sperm; transgenerational stress.

Figure 1.

A summary of how paternal stress alters behavioral outcomes of offspring rodents. (A) A schematic of developmental of male sex cells and mouse development. (B) Effects of paternal stress during either early life, adolescence, or adulthood on depression- and anxiety-related behaviors in offspring. Neonatal or adolescence stress results in decreased anxiety- like behaviors in offspring when fathers are exposed to either social or asocial stress. However, only social paternal stress results in increased depression- like behaviors in offspring. While little information is available regarding how paternal stress during adulthood (dotted line) alters baseline behavioral phenotypes in offspring, one study has found changed in offspring behavior in social stress paradigms.