Programming effects of maternal stress during lactation: Investigating offspring neuroendocrine, behavioral and immunological responses to early life adversity in a pig model

• Applicants: Professorin Dr. Ulrike Gimsa; Liza Moscovice, Ph.D.
• Subject Area: Animal Breeding, Animal Nutrition, Animal Husbandry ; General, Cognitive and Mathematical Psychology ; Developmental Neurobiology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 447979970

In humans, exposure to early life adversity (ELA), including chronic stress or neglect, is a predictor of childhood mortality and increases the risks for a range of health problems in adulthood. The aim of our project is to introduce a novel porcine model to investigate the influence of maternal stress during lactation on the development of behavioral, neuroendocrine and immunological responses in offspring, via ‘programming effects’. As the basis for our research, sows and their offspring will be independently exposed to low or high levels of stress during the lactational period. To model high maternal stress, we will repeatedly administer the HPA-axis stimulating adrenocorticotropic hormone (ACTH) to test sows, while control sows will receive saline. We will investigate pathways by which programming effects may be transmitted to offspring, via alterations in milk composition or maternal care. Offspring from different early maternal environments will also undergo an acute maternal separation either alone (high stress condition) or with littermates present for social support (low stress condition). We will characterize the combined effects of early maternal environment and having access to social support during stressors on piglets’ coping abilities. We will measure piglet behavioral responses to reunions with mothers and will collect blood samples to measure cortisol as an indicator of stress, the neuropeptide hormone oxytocin (OXT), which may mediate the stress buffering effects of social support, and alterations in immune cell composition and responses. A subset of piglets will be sacrificed following the acute maternal separation, to investigate the impacts of early maternal environment and varied social support on gene expression of cortisol receptors, OXT and its receptors and other molecules that may regulate HPA-axis activity and mediate brain-immune cross-talk. The remaining pigs will be weaned in mixed groups with equal numbers of offspring from high- and low-stress mothers. We will measure long-term impacts of early maternal environment on responses to environmental and social challenges later in life, including weaning and exposure to novelty. We will collect behavioral data and saliva samples to characterize OXT and cortisol responsivity to stressors. We will also measure working memory to index cognitive capacities. Pigs will undergo an ACTH challenge to determine HPA-axis reactivity and effects on immune responses. A subset of the remaining pigs will be sacrificed to measure gene expression as described after maternal separation, to determine long-term programming effects of ELA on hypothalamic and limbic brain development. In addition to the translational implications in identifying potential mediators of programming effects in humans, our research will also have applied value by identifying interventions that may reduce piglet mortality and improve welfare of pigs in livestock farming.

• DFG Programme: Research Grants