A cellular defense memory imprinted by early life toxic stress

Stress exposure early in life is implicated in various behavioural and somatic diseases. Experiences during the critical perinatal period form permanent, imprinted memories promoting adult survival. Although imprinting is widely recognized to dictate behaviour, whether it actuates specific transcriptional responses at the cellular level is unknown. Here we report that in response to early life stresses, Caenorhabditis elegans nematodes form an imprinted cellular defense memory. We show that exposing newly-born worms to toxic antimycin A and paraquat, respectively, stimulates the expression of toxin-specific cytoprotective reporters. Toxin exposure also induces avoidance of the toxin-containing bacterial lawn. In contrast, adult worms do not exhibit aversive behaviour towards stress-associated bacterial sensory cues. However, the mere re-encounter with the same cues reactivates the previously induced cytoprotective reporters. Learned adult defenses require memory formation during the L1 larval stage and do not appear to confer increased protection against the toxin. Thus, exposure of C. elegans to toxic stresses in the critical period elicits adaptive behavioural and cytoprotective responses, which do not form imprinted aversive behaviour, but imprint a cytoprotective memory. Our findings identify a novel form of imprinting and suggest that imprinted molecular defenses might underlie various pathophysiological alterations related to early life stress. © 2019, The Author(s)

Offspring Hormones Reflect the Maternal Prenatal Social Environment: Potential for Foetal Programming?

Females of many species adaptively program their offspring to predictable environmental conditions, a process that is often mediated by hormones. Laboratory studies have shown, for instance, that social density affects levels of maternal cortisol and testosterone, leading to fitness-relevant changes in offspring physiology and behaviour. However, the effects of social density remain poorly understood in natural populations due to the difficulty of disentangling confounding influences such as climatic variation and food availability. Colonially breeding marine mammals offer a unique opportunity to study maternal effects in response to variable colony densities under similar ecological conditions. We therefore quantified maternal and offspring hormone levels in 84 Antarctic fur seals (Arctocephalus gazella) from two closely neighbouring colonies of contrasting density. Hair samples were used as they integrate hormone levels over several weeks or months and therefore represent in utero conditions during foetal development. We found significantly higher levels of cortisol and testosterone (both P < 0.001) in mothers from the high density colony, reflecting a more stressful and competitive environment. In addition, offspring testosterone showed a significant positive correlation with maternal cortisol (P < 0.05). Although further work is needed to elucidate the potential consequences for offspring fitness, these findings raise the intriguing possibility that adaptive foetal programming might occur in fur seals in response to the maternal social environment. They also lend support to the idea that hormonally mediated maternal effects may depend more strongly on the maternal regulation of androgen rather than cortisol levels