Yu, Liang-en2023-10-092023-10-092023https://udspace.udel.edu/handle/19716/33433Developmental plasticity during the prenatal and early postnatal periods of life significantly contributes to animals’ organ development and functions. In such a sensitive window, the animals quickly sense and adapt to the surrounding environment, efficiently building up organ machinery that is suitable for survival. These adaptations may be irreversible throughout the later life, and either lead animals to beneficial strategies for survival or predispose animals to a detrimental risk of disease. The gastrointestinal (GI) tract is a highly adaptive organ dealing with the constant changes of the complicated luminal environment. It senses and absorbs nutrients while selectively blocking the intrusion of harmful antigens and pathogens for animals. However, whether and how early life events affect later life intestinal function is not fully studied in agricultural animals. ☐ Optimal intestinal epithelial functions are largely contributed by the renewal and maturation of epithelial cell populations (such as enterocytes, goblet cells, Paneth cells, and enteroendocrine cells), which are actively generated by intestinal epithelial stem cells (IESC). Given the rapid turnover rate of epithelial cells (every 3~5 days), any long-lasting alterations in epithelial functions could be potentially originated from intrinsic alternations in IESCs. During early development, the relatively high number and activity of stem cells allows more efficient adaptation to the environment challenges than later life. This sets up an intestinal machinery that supports long term survival. Whether early life events influence IESC activities and epithelial cell populations is largely unknown. ☐ In this dissertation, we utilized broiler chickens and pigs as animal models to identify effects of 3 early life events on intestinal development and functions, including 1) 72h delayed post-hatch feeding stress (DF) in chickens, 2) in-ovo nutritional intervention in chickens, and 3) early weaning stress (EW) in pigs. We applied the unique Ussing chamber electrophysiological technique and cutting-edge enteroids culture technique to identify intestinal stem cell activities, epithelial cell population, barrier function, nutrient sensing and transport functions at acute and long-term stage post early life events. Our results showed that both DF and EW decreased villi surface area and intestinal barrier function. Interestingly, the relocation of enteroendocrine cells (EEC) was found in ileum tissue, which paralleled with the decreasing of nutrient sensing function and serum glucagon-like peptide 2 (GLP2) concentration. The decreasing of enteroid formation rate, size, and expansion in basolateral-out enteroids, which indicated the activity of IESC was decreased dramatically in both DF chickens and EW pigs. Moreover, the differentiation ability of IESC into enterocytes and EEC decreased in EW pigs’ enteroids. On the other hand, in-ovo Gln injection increased intestinal growth, development and functional maturation, which indicated the early life nutrient intervention is suitable for improving intestinal development. Further, we demonstrated the novel intestinal functional analysis for gut permeability, glucose absorption, and proliferation. ☐ Overall, we found the similarity in gut development between the mammalians and non-mammal oviparous animals. The early life events interferences intestinal development and functions via alterations of IESC’s proliferation and differentiation activities. The added nutrients and stress signals both contributed to the long-term changes in the number and function of epithelial absorptive and secretory cell populations, which increased the survival efficiency. Understanding IESC regulation during early life development will shed light on identifying novel strategies for optimal gut health and regeneration under stress.Enteroendocrine cellsEnteroidsGut healthIntestinal developmentStem cellsGastrointestinalThesis1413968141https://doi.org/10.58088/mzdv-f9502023-09-20en