Intrauterine Growth Restriction Modifies the Developmental Pattern of Intestinal Structure, Transcriptomic Profile, and Bacterial Colonization in Neonatal Pigs

Abstract

Neonates with intrauterine growth restriction (IUGR) are prone to suffer from digestive diseases. Using neonatal pigs with IUGR, we tested the hypothesis that IUGR may induce alterations in the developmental pattern of intestinal barrier and thereby may be responsible for IUGR-associated increased morbidity. Piglets with a birth weight near the mean birth weight (+/-0.5 SD) were identified as normal birth weight (control) and piglets with a mean -2 SD lower birth weight (-30%) were defined as piglets with IUGR. The developmental pattern of intestinal structure, transcriptomic profile, and bacterial colonization was investigated from birth to d 5 postnatal. At birth, intestinal weight and length, ileal and colonic weight per unit of length, and villous sizes were lower (P < 0.05) in piglets with IUGR than in same-age control piglets. These IUGR-induced intestinal alterations further persisted, although they were less marked at d 5. Counts of adherent bacteria to ileal and colonic mucosa were greater (P < 0.05) in 2-d-old piglets with IUGR than in same-age control piglets. Dynamic analyses of the transcriptomic profile of the intestine revealed molecular evidence of IUGR-induced intestinal growth impairment that may result from a change in the cell proliferation-apoptosis balance during the first days of life, while a protective process would occur later on. In addition, changes in the expression of several genes suggest a pivotal role of both glucocorticoids and microbiota in driving IUGR intestinal development during the neonatal period.

Nutrient-intake-level-dependent regulation of intestinal development in newborn intrauterine growth-restricted piglets via glucagon-like peptide-2

“…Recent clues from transcriptomic profiles of the intestine have revealed molecular evidence of IUGR-induced impairment in intestinal growth that may result from changes in the cell proliferation-apoptosis balance (D'Inca et al, 2010). For the control of cell apoptosis, p53 has received significant attention (Miyashita and Reed, 1995).…”

“…IUGR has been primarily attributed to placental insufficiency during the intrauterine phase (Wu et al, 2006), and can be regarded as the failure of a fetus to reach its genetic growth potential. The small intestine, which is the portal for absorption of virtually all nutrients into the blood stream, can be dramatically altered in IUGR neonates (D'Inca et al, 2010). This, along with compromised intestinal growth and development, can lead to atrophy of the intestine and impairment of nutrient absorption and utilization (Weaver et al, 1991;Baserga et al, 2004;Bjornvad et al, 2005).…”

Ghrelin in the gastrointestinal tract and blood circulation of perinatal low and normal weight piglets

“…Interestingly, a recent study has shown that enteral administration of ghrelin in neonatal piglets influenced both intestinal growth and intestinal epithelial cell turnover (Slupecka et al, 2012). As IUGR induces intestinal growth impairment (D'Inca et al, 2010b), the knowledge of an altered gastric GC distribution in the SGA piglets may be used for the preparation of milk formulas for neonates suffering from an insufficient development of the gastrointestinal system.…”

“…The high morbidity associated with IUGR in humans and animals can be attributed to an impaired development of various organs, such as those of the gastrointestinal system (D'Inca et al, 2010b). Consequently, IUGR neonates are prone to food intolerance, decreased fat absorption and digestive diseases during early postnatal life (Xu et al, 1994;Lee et al, 2001).…”

“…The porcine model represents most of the symptoms associated with the metabolic syndrome in adult life seen in the IUGR children, such as increased adiposity (Poore and Fowden, 2004) and glucose intolerance (Poore and Fowden, 2002). In addition, the IUGR alters gastrointestinal morphology in the postnatal piglets (Xu et al, 1994;Wang et al, 2005;D'Inca et al, 2010b). However, it is not known whether these alterations persist until weaning.…”