338 - Paneth Cell Ontogeny in Term and Preterm Ovine Models

Friday, April 28, 2023

5:15 PM – 7:15 PM ET

Poster Number: 338
Publication Number: 338.133

Anjali Cera, University of California Davis Children's Hospital, Sacramento, CA, United States; Geoanna M. Bautista, University of California, Davis, School of Medicine, Sacramento, CA, United States; Sylvia F. Gugino, State University of New York at Buffalo, Buffalo, NY, United States; satyanarayana Lakshminrusimha, UC Davis Children's Hospital, Sacramento, CA, United States; Steven McElroy, UC Davis, Sacramento, CA, United States

Presenting Author(s)

AC

Anjali Cera, MD (she/her/hers)

Neonatal-Perinatal Fellow
University of California Davis Children's Hospital
Sacramento, California, United States

Background:

Necrotizing enterocolitis (NEC) remains a leading cause of morbidity and mortality in premature infants. Paneth cells (PC) are key regulators of the innate immune system and have been implicated in the development of NEC. However, ontogeny and distribution of PCs in a large, translatable mammalian model such as the neonatal lamb remain poorly characterized.

Objective: Compare distribution and density of PCs between premature and term ovine intestines and the impact of hypoxic-ischemic stress.

Design/Methods:

Whole intestinal specimens were collected from full-term lambs (gestational age-GA 140-141d, n=15), preterm lambs (GA 126-127d, n=13), and preterm lambs that underwent induced bradycardia and hypoxia by umbilical cord occlusion (n=6). PCs were quantified per crypt for at least 100 crypts per sample. ANOVA and Mann-Whitney statistical tests were used.

Results:

PC density in the term lamb showed significant variation among the small intestine regions, with the greatest PC density in the ileum and none in the colon (p< 0.0001). Preterm lambs had significantly decreased ileal PC density compared to term labs (p=0.04). Hypoxic-ischemic insult further reduced the density of ileal PCs in preterm lambs (p=0.0024).

Conclusion(s):

Our study suggests that density of PCs in neonatal lambs parallels that in human neonates with increased density found in the distal small intestine (the most common site for NEC). Additionally, like human neonates, this study suggests that ovine PC density increases throughout gestation. Ileal PCs in the ovine model were also found to be susceptible to hypoxic-ischemic stress. Additional studies can be performed to elucidate the role of PCs in the etiology of NEC, particularly in the context of different types of hypoxic-ischemic stressors that can be simulated in the ovine model.