Pre- and post-natal stress programming: from genes to physiology

Marasco, Valeria (2014) Pre- and post-natal stress programming: from genes to physiology. PhD thesis, University of Glasgow.

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In a variety of vertebrate species, early life environmental cues are important drivers of an individual’s phenotypic trajectories, priming physiological pathways, with consequences for growth, reproductive-related traits and lifespan. These phenotypic responses are believed to be adaptive in the short-term, but may impinge on health and survival over the long-term. Much of the work in this field has focused on the potential constraints imposed on animals after exposure to early life adversities, including nutritional deficit, sibling competition, and high predator pressure. Such stressful experiences can result in direct, but also indirect (via the maternal route) increases in the exposure to glucocorticoid stress hormones in the developing individuals. Glucocorticoids, whose production and secretion is regulated by the Hypothalamic-Pituitary-Adrenal axis (HPA axis), have been hypothesised to be the main candidates mediating the programming effects of developmental stress. Earlier predictions based on this assumption came from studies conducted in mammals. In mammals it is particularly difficult to manipulate exposure to circulating hormones in developing individuals because of the physiological intimacy between mother and offspring via the placenta and lactation. Here, I circumvent this complicating factor by using the precocial Japanese quail as a study species. In chapter 2 I measure corticosterone (B, the main avian glucocorticoid) stress responses to a standardised environmental stressor in growing quail aged 8- and 16-days-old. The results are consistent with those previously reported in other precocial birds, showing that the magnitude of the stress response (i.e. peak B within 30 min period) is higher in the 8- than the 16-day-old hatchlings. I find no differences in baseline B concentrations between the two groups. I then describe the main experiment in which I elevate B concentrations in ovo and/or in the endogenous circulation of the hatchlings (oral B administration from day 5 to day 19 post-hatching) in order to obtain four distinct phenotypes: pre-hatching B-treated birds, post-hatching B-treated birds, both pre- and post-hatching B-treated birds, and controls. I examine the specific and combined effects of pre- and post-hatching B on (1) growth trajectories and physiological stress responses before sexual maturity (post-hatch day 22) and upon adulthood (post-hatch day 64); (2) adult gene expression patterns within the hippocampus and hypothalamus, and (3) oxidative stress in the blood and the brain in the adults. The main results of Chapter 3 show that post-hatching B, regardless of pre-hatching experiences, decrease HPA axis responsiveness in the juveniles, but only in the female quail; whilst pre-hatching stress, when not combined with post-hatching B, increase HPA responsiveness in both sexes upon adulthood. I also show that both pre- and post-hatching B induce short-term alterations in triglyceride basal concentrations, which are linked with the sex and basal glucose concentrations of the birds; the effects of pre-hatching B exposure were visible also upon adulthood with sex-specific alterations on basal glucose concentrations. Overall these results suggest that early life stress can trigger both transient and permanent physiological changes, depending on the sex and the quality of both the pre- and post-hatching environment. In Chapter 4 I show that the gene expression responses to pre- and post-hatching B are overall subtle, results similar to those reported in previous genomic studies that have manipulated early life rearing environments. The effects are, however, distinguishable, strongly tissue-specific and involve well characterised key candidate genes in the regulation of the HPA axis. These data also suggest important novel regulatory mechanisms, likely linked with cellular redox state, which may be driving the long-term effects of developmental stress. Finally, in chapter 5, I show that developmental B induces alterations in the basal antioxidant defences upon adulthood. The magnitude of these effects, once more, depends upon the timing of exposure, interactions between the pre- and post-hatching B and the tissue examined. As there are no differences in terminal oxidative damage, these results suggest that the B-treated birds could avoid oxidative stress via altering body oxidative defences. In summary, my findings throughout this thesis, illustrate the complexity of glucocorticoid programming and the importance of integrating analyses at multiple levels, from physiology to genome-wide investigations. The results of this thesis also strengthen the importance of examining the effects of early life stress over differing life stages in order to consider the overall balance of costs and benefits that may ultimately affect Darwinian fitness and survival.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: early life stress, pre- and post-natal glucocorticoid programming, corticosterone, transcriptomics, RNA-seq, oxidative stress
Subjects: Q Science > QL Zoology
Q Science > QP Physiology
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
Supervisor's Name: Spencer, Karen Anne and Robinson, Jane and Herzyk, Pawel
Date of Award: 2014
Depositing User: Valeria Marasco
Unique ID: glathesis:2014-5000
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 08 Apr 2014 09:31
Last Modified: 07 Mar 2017 10:21

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