Ancestral prenatal stress in F3 and F4 rats: the match/mismatch hypothesis

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Reynolds, Teddi
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Lethbridge, Alta. : University of Lethbridge, Dept. of Neuroscience
Cumulative lifetime stress can have detrimental impacts on developmental trajectories and life outcomes. The impacts of stress over multiple generations become a more complex issue. This thesis aimed to understand the impacts of prenatal stress exposure over four generations of rats and worked to develop a maternal stress index (MSI) that adequately quantifies the physiological dysregulation induced by stress. This study assessed the impacts of two different protocols of ancestral prenatal stress in rats. The models included transgenerational prenatal stress (TPS) where the filial 0 generation (F0) dams experienced mild gestational stress, and each subsequent generation afterwards experienced unstressed pregnancies, and multigenerational prenatal stress (MPS), in which each generation experienced stress during gestation. The first study investigated the impacts on F2 dams and F3 young offspring and revealed that the novel MSI was sensitive to maternal stress and predicted the behavioural phenotype in the offspring. The TPS lineage was linked to more adverse pregnancy and developmental outcomes than the MPS lineage. The second study measured the impacts of TPS and MPS on the F4 generation. It was determined that some of the negative impacts found in the F3 generation had disappeared, but reduced exploration in MPS animals was observed. The third and final study focused on the aging F4 generation of the MPS lineage and found that anxiety behaviour at postnatal day 110 was able to predict anxiety at 12 months of age. It was also determined that the lifespan of MPS animals lengthened compared to controls. These studies reveal patterns of generational adaptation to stress and postulate models that predict lifetime health trajectories.
All procedures in this study were approved by the University of Lethbridge Animal Care Committee in compliance with the standards set out by the Canadian Council for Animal Care. The authors gratefully acknowledge support with the experiments by Sophia Vathracoulis.
Ancestral prenatal stress , Maternal stress index , Gestational stress , Pregnant rats , Physiological dysregulation