Evidence of alterations in the learning and memory in offspring of stress-induced male rats

Objectives There is extensive data pointing to offspring outcomes related to maternal life incidents, but there is less research concerning the association between paternal life events and progeny brain development and behaviour. As male gametogenesis is a continuous process, the incidences happening in life can modify the epigenetic regulation, altering the offspring’s development and behaviour. The present study evaluates the effects of paternal stress during different life periods on their offspring’s learning ability, memory, morphological and biochemical changes in the prefrontal cortex and hippocampus in the rat model. Methods Four weeks’ old male rats were subjected to five variable stressors at the rate of one per day. Stress received male rats were bred with naive female rats for 1 to 3 nights. The offspring’s learning and memory were assessed by the Morris water maze test and automated Y maze. Following behavioural studies, offspring were euthanized to examine global DNA methylation, neurotransmitter levels, namely acetylcholine, glutamate in the hippocampus and frontal cortex. Results The offspring of stress-induced animals exhibited a delay in acquiring learning and defect in memory and altered global DNA methylation in the hippocampus (p=0.000124). There was significant reduction of acetylcholine and glutamate levels in hippocampus (p=0.000018, p=0.00001, respectively) and in prefrontal cortex (p=0.00001, p=0.00001, respectively). HPA axis of offspring was altered considerably (p=0.00001). The histomorphometry of the prefrontal cortex and different hippocampal regions revealed a statistically significant (p<0.05) reduction in neuronal numbers in the offspring of stressed animals compared to that of control. These impacts were markedly high in the offspring of fathers who received stress during both pubertal and adult periods. Conclusions The findings of this study demonstrate that paternal stress can impact offspring learning and memory.

Paternal Postpartum Bonding and Its Predictors in the Early Postpartum Period: Cross-Sectional Study in a Polish Cohort

Introduction: Parental postpartum bonding has been studied by many researchers focusing on maternal bonding. The objective of this study was to examine the psychological and socio-demographic predictors of paternal postpartum bonding in the early postpartum period.Methods: In this cross-sectional study, 131 couples (fathers median age of 32.37 years, SD = 4.59; mothers median age of 30.23 years, SD = 3.90) of newborns from full-term pregnancies were recruited from November 2019 until March 2020. The primary outcome was paternal postpartum bonding as measured by the Postpartum Bonding Questionnaire (PBQ). Secondary outcomes included: maternal and paternal anxiety [with the Generalized Anxiety Disorder (GAD) Assessment]; maternal and paternal stress [with the Parental Stress Scale (PSS)]; maternal depressive symptoms [with the Edinburgh Postpartum Depression Scale (EPDS)]; and maternal and paternal socio-demographic variables as fathers’ presence at childbirth, education level, age, and parental experience.Results: Paternal postpartum bonding was significantly correlated with paternal anxiety (moderate strength), maternal stress (strong correlation), and maternal postpartum bonding. No significant correlations between paternal postpartum bonding, maternal depression symptoms, and maternal anxiety were found. The mediating role of paternal stress in paternal postpartum bonding was proven. Paternal anxiety strengthens paternal stress (b = 0.98). Further, a high level of paternal stress disrupts paternal postpartum bonding (b = 0.41). Results of regression analyses have revelated that maternal infant bonding (p &lt; 0.01) and paternal stress (p &lt; 0.01) are the only predictors of parental postpartum bonding across all included variables. None of investigated socio-demographic variables were associated with paternal postpartum bonding.Conclusion: Notwithstanding limitations, the current findings add to a growing body of literature on paternal postpartum bonding. The results have shown that paternal mental health is related to parental postpartum bonding directly after delivery.Clinical Trial Registration:ClinicalTrials.gov Identifier: NCT04118751.

Single paternal Dexamethasone challenge programs offspring metabolism and reveals circRNAs as novel candidates in RNA-mediated inheritance

SummarySingle traumatic events that elicit an exaggerated stress response can lead to the development of neuropsychiatric conditions. Studies in mice suggests germline RNA as a mediator of effects of chronic environmental exposures to the progeny. The effects of an acute paternal stress exposure on the germline and their potential consequences on offspring remain unknown. We find that acute administration of an agonist for the stress- sensitive Glucocorticoid receptor, using the common corticosteroid Dexamethasone, affects the RNA payload of post-meiotic transcriptionally silent, mature sperm as soon as 3 hours post exposure. It further impacts early embryonic transcriptional trajectories, as determined by single embryo sequencing, and metabolism in the offspring. Importantly, we show persistent regulation of tRNA fragments in sperm and the descendant 2-cell- embryos, suggesting actual transmission from sperm to embryo. Lastly, we unravel environmentally induced alterations in the previously underconsidered class of sperm circRNAs, and their targets in the early embryo, highlighting this class as a novel candidate in RNA-mediated inheritance.

Epigenetic Mechanisms of Paternal Stress in Offspring Development and Diseases

The major biological function of the sperm cell is to transmit the paternal genetic and epigenetic information to the embryo as well as the following offspring. Sperm has a unique epigenome. An increasing body of epidemiological study supports that paternal stress induced by environmental exposures and lifestyle can modulate the sperm epigenome (including histone modification, DNA methylation, and noncoding RNA expression), sperm-egg fusion, embryo development, and offspring health. Based on the existing literature, we have summarized the paternal exposure on sperm epigenome along with the representative phenotypes of offspring and the possible mechanism involved.

Limitations to intergenerational inheritance: subchronic paternal stress preconception does not influence offspring anxiety

Independent studies have observed that a paternal history of stress or trauma is associated with his children having a greater likelihood of developing psychopathologies such as anxiety disorders. This father-to-child effect is reproduced in several mouse models of stress, which have been crucial in developing a greater understanding of intergenerational epigenetic inheritance. We previously reported that treatment of C57Bl/6J male breeders with low-dose corticosterone (CORT) for 28 days prior to mating yielded increased anxiety-related behaviours in their male F1 offspring. The present study aimed to determine whether subchronic 7-day CORT treatment of male mice just prior to mating would be sufficient to induce intergenerational modifications of anxiety-related behaviours in offspring. We report that subchronic CORT treatment of male breeders reduced their week-on-week body weight gain and altered NR3C1 and CRH gene expression in the hypothalamus. There were no effects on sperm count and glucocorticoid receptor protein levels within the epididymal tissue of male breeders. Regarding the F1 offspring, screening for anxiety-related behaviours using the elevated-plus maze, light–dark box, and novelty-suppressed feeding test revealed no differences between the offspring of CORT-treated breeders compared to controls. Thus, it is crucial that future studies take into consideration the duration of exposure when assessing the intergenerational impacts of paternal health.