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.

Transgenerational modification of dopaminergic dysfunctions induced by maternal immune activation

“…The paternal mode of the transgenerational modification of DA functions is consistent with our previous study [9], which identified a critical role of the paternal lineage in mediating non-genetic inheritance of social and fear-related abnormalities after MIA. The paternal mode of transmission is also consistent with other models of early-life adversities, such as prenatal or neonatal stress [40]. Hence, there is increasing evidence to suggest that stable epigenetic modifications in sperm cells may represent a mechanism by which exposure to environmental adversities, including immune challenges [40], can induce pathological effects across generations.…”

Intermittent Hypoxia Promotes Functional Neuroprotection from Retinal Ischemia in Untreated First-Generation Offspring: Proteomic Mechanistic Insights

“…Evidence supporting the nongenetic inheritance of disease susceptibility as a result of adverse stress-induced epigenetic modifications to the parental germline continues to grow. 6 – 11 Results of the present study juxtapose these findings by showing for the first time, to the best of our knowledge, that exposure of adult mice to repetitive systemic hypoxia during adulthood—and prior to conception—protects against retinal ischemic injury in their adult F1-generation progeny. Thus, not only can disease burden be inherited across generations as a result of maladaptive responses on the part of parents, but progeny can also inherit disease resilience secondary to adaptive responses on the part of their parental lineage to beneficial stress stimuli that promote such phenotypes.…”

“…Accumulating evidence documents the intergenerational and transgenerational passage of phenotypes in a number of species, 6 – 8 including mammals. 9 – 11 That this also occurs in humans, beyond imprinting, is strongly suggested by a broad set of elegantly curated epidemiological data. 12 , 13 The vast majority of research in these aforementioned fields of study has focused on identifying pathological phenotypes and disease susceptibility resulting from previously presented adverse stressors.…”

Intermittent hypoxia promotes functional neuroprotection from retinal ischemia in untreated first-generation offspring

“…Evidence supporting the nongenetic inheritance of disease susceptibility as a result of environmentally-induced epigenetic modifications to the parental germline continues to grow (6)(7)(8)(9)(10)(11). conversely, passing the resilient phenotype to the F2 generation and beyond would be unnecessary if the potential for these subsequent generations to experience this injury is no longer present.…”

“…In fact, epigenetic modifications secondary to stress and environmental change can not only affect phenotypes across the lifespan, but can also affect phenotypes in progeny. Accumulating evidence documents the intergenerational and transgenerational passage of epigenetically-induced phenotypes in a number of species (6)(7)(8), including mammals (9)(10)(11). That this also occurs in humans, beyond imprinting, is strongly suggested by a broad set of elegantly curated epidemiological data (12,13).…”