ABSTRACT
BACKGROUND: Intestinal epithelial stem cells (ISC) are responsible for epithelial regeneration and are critical to the intestine's ability to regain barrier function following injury. Evaluating ISC biomarker expression in cases of small intestinal strangulation (SIS) may provide insight into clinical progression. OBJECTIVES: Intestinal resection margins from cases of SIS were evaluated to determine if (1) evidence of injury could be identified using histomorphometry, (2) ISC biomarker expression was decreased in the proximal resection margin compared to control and distal resection margin, and (3) the ISC biomarker expression was associated with the number of preoperative risk factors negatively related to outcome, post-operative complications, or case outcome. STUDY DESIGN: Retrospective cohort study. METHODS: Intestinal samples were obtained intraoperatively from resection margins of adult horses with SIS and horses euthanised for reasons unrelated to colic. Preoperative risk factors negatively related to outcome, post-operative complications, and case outcome were obtained from medical records. Horses were grouped as euthanised intraoperatively, postoperatively, or survived to discharge. Histomorphometry and immunofluorescence were performed to evaluate tissue architecture and ISC and progenitor cell number. Groups were compared using one-way ANOVA. Associations between biomarker expression and the number of preoperative risk factors and post-operative complications negatively related to outcome were determined using linear regression modelling. RESULTS: Thirty-six cases of SIS were evaluated. Ki67+ cell counts were decreased in the proximal (mean = 15.45 cells; 95% CI = 10.27-20.63; SD = 4.17; p = 0.02) and distal resection margins (mean = 15.05; 95% CI = 8.46-21.64; SD = 4.141; p = 0.03) in horses euthanised postoperatively compared to control (mean = 23.62 cells; 95% CI = 19.42-27.83; SD = 5.883). In the distal resection margin, an increase in SOX9+ Ki67+ cells were associated with a decrease in the total number of preoperative risk factors negatively related to outcome (95% CI = 0.236-1.123; p = 0.008, SE = 0.1393). MAIN LIMITATIONS: Small population size. CONCLUSIONS: Proliferating cell and ISC numbers may be associated with case outcome.
ABSTRACT
Previous work in our lab has shown that early-life infection affects female reproductive physiology and function (i.e., smaller ovaries, abnormal estrous cycles) and alters investigation and aggression towards male conspecifics in a reproductive context. Although many studies have investigated the effects of postnatal immune challenge on physiological and behavioral development, fewer studies have examined whether these changes have ultimate effects on reproduction. In the current study, we paired Siberian hamsters (Phodopus sungorus) and simulated a bacterial infection in early life by administering lipopolysaccharide (LPS) to male and female pups on pnd3 and pnd5. In adulthood, hamsters were paired with novel individuals of the same sex, and we scored an array of social behaviors (e.g., investigation, aggression). We then paired animals with individuals of the opposite sex for 5 consecutive nights, providing them with the opportunity to mate. We found that females exhibited impaired reproductive physiology and function in adulthood (i.e., smaller ovaries and abnormal estrous cycles), similar to our previous work. However, both LPS-treated males and females exhibited similar same-sex social behavior when compared with saline-treated controls, they successfully mated, and there were no significant changes in fecundity. These data suggest that the physiological changes in response to neonatal immune challenge may not have long-term effects on reproductive success in a controlled environment. Collectively, the results of this study are particularly important when investigating the relationships between physiology and behavior within an ultimate context. Animals exposed to early-life stress may in fact be capable of compensating for changes in physiology in order to survive and reproduce in some contexts.
