Endoplasmic Reticulum Stress Contributes to Intestinal Injury in Intrauterine Growth Restriction Newborn Piglets

Intrauterine growth retardation (IUGR) in piglets is associated with a high rate of morbidity and mortality after birth due to gut dysfunction, and the underlying mechanisms remain poorly understood. This study selected six pairs of IUGR newborn male piglets and normal birth weight newborn piglets (Large White × Landrace) to investigate differences in intestinal structure and digestive functions, intestinal ERS and apoptosis, intestinal barrier function, and inflammatory response. The results showed that IUGR significantly reduced the jejunal villi height (<i>p <</i> 0.05) and the ratio of villus-height-to-crypt-depth (<i>p</i> = 0.05) in neonatal piglets. Additionally, the microvilli in the jejunum of IUGR neonatal piglets were shorter than those in normal-weight piglets, and swelling of the mitochondria and expansion of the endoplasmic reticulum were observed. IUGR also significantly reduced serum glucose and lactase levels (<i>p</i> < 0.05) while significantly increasing mRNA levels of jejunal <i>IRE1α</i>, <i>EIF2α</i>, <i>CHOP</i>, <i>Bax</i>, <i>Caspase9</i>, <i>Mucin2</i>, <i>Claudin-1</i>, <i>Occludin</i>, <i>ZO-1</i>, <i>Bcl-2</i>, <i>IL-6</i>, and <i>IFN-γ</i> (<i>p</i> < 0.05), as well as GRP78 protein levels in neonatal piglets (<i>p</i> < 0.05). These findings suggest that IUGR impairs intestinal structure and barrier function in newborn piglets by enhancing intestinal inflammatory responses, activating intestinal ERS and the signaling pathways related to the unfolded protein response, thereby inducing ERS-related apoptosis.