Intrauterine growth retardation enhances intestinal autophagy and proliferation in rat pups responding to colostrum

Abstract

This study aimed to investigate responsible mechanisms for rapid intestinal catch-up growth in intrauterine growth restriction (IUGR) pups via analysis of autophagy, apoptosis and proliferation in a rat model. Twenty primiparous dams were assigned into two groups as 1) dams with feed ad libitum (Adlib) and 2) dams with 50% feed restriction from gestational day 10 to 21 to achieve normal birth weight (NBW) and IUGR pups, respectively. Litter size and pup weight were recorded at parturition and 8 pups were kept in each litter to have sufficient colostrum for 24 h. Subsequently, 2 pups from each litter were decapitated. Results indicated that feed restriction dams had similar litter size with rats in Adlib group although produced IUGR pups. Histological analysis indicated that IUGR rats had decreased villus height and surface area in jejunum. There was an accumulation of autophagosomes in jejunal mucosa of IUGR pups, however, the mitochondria and microvilli were unaffected. mRNA expressions of WIPI1, MAP1LC3B, Atg13, ULK1 and Beclin1 were increased, and mTOR expression was decreased in jejunum of IUGR, which also had lower Bcl-2 mRNA expression, increased caspase 9 and relative increased ki67 mRNA expression. Results suggested that after feeding colostrum, IUGR pups had impaired jejunum with unaffected mitochondrial histology. Enhanced intestinal autophagy under low-stress conditions might improve intestinal proliferation, which may be contributed to the rapid intestinal catch-up growth.

Keywords

• autophagy
• colostrum
• intrauterine growth restriction
• intestinal proliferation
• apoptosis