Intrauterine Growth Restriction Impairs Small Intestinal Mucosal Immunity in Neonatal Piglets

Abstract

SummaryIntrauterine growth restriction (IUGR) is a very common problem in both piglet and human neonate populations. We hypothesized that IUGR neonates have impaired intestinal mucosal immunity from birth. Using neonatal piglets as IUGR models, immune organ weights, the weight and length of the small intestine (SI), intestinal morphology, intraepithelial immune cell numbers, levels of cytokines and immunoglobulins, and the relative gene expression of cytokines in the SI were investigated. IUGR neonatal piglets were observed to have lower absolute immune organ weight and SI length, decreased relative weights of the thymus, spleen, mesenteric lymph node, and thinner but longer SIs. Damaged and jagged villi, shorter microvilli, presence of autophagosomes, swelled mitochondria, and decreased villus surface areas were also found in the SIs of IUGR neonatal piglets. We also found a smaller number of epithelial goblet cells and lymphocytes in the SIs of IUGR neonates. In addition, we detected reduced levels of the cytokines TNF-α and IFN-γ and decreased gene expression of cytokines in IUGR neonates. In conclusion, IUGR was shown to impair the mucosal immunity of the SI in neonatal piglets, and the ileum was the major site of impairment. (J Histochem Cytochem 62:510-518, 2014)

Altered tissue mineralization, increased hepatic lipid and inhibited autophagy in intrauterine growth retardation piglets

“…Total RNA of the liver was extracted with Trizol reagents, and reverse transcription was conducted as described by Dong et al (2014). Briefly, after the RNA quality had been verified by a Thermo Fisher Scientific Nanodrop 2000 spectrophotometer (ratios of absorption including 260/280 nm and 260/230 nm between 1.90 and 2.05) and by agarose gel electrophoresis, 2 μg RNA were incubated at 72 °C with random primer (Promega, Belgium) for 5 min, then incubated for 1 hour with reverse transcription mixture (Takara, Dalian, China).…”

“…All the data were processed with the student t-test of the SPSS statistical package (Version 20.0, SPSS Inc., Chicago, IL) as described by Dong et al (2014).Results were shown as mean ± SE. P value below 0.05 was regarded as significant.…”

Impaired intestinal mucosal immunity is associated with the imbalance of T lymphocyte sub-populations in intrauterine growth-restricted neonatal piglets

“…CD4 + cells are T helper cells, which can produce cytokines and defend the host against extra-cellular microbes, while CD8 + cells are cytotoxic cells, which can recognize and kill host cells infected with intracellular microbes (Abbas et al, 1994). Our previous study has demonstrated that IUGR neonatal piglets exhibit a weaker cytokine secretion ability in the small intestines (Dong et al, 2014). We hypothesized this weaker secretion might be caused by the lower numbers of CD4 + and CD8 + lymphocytes in IUGR neonatal piglets.…”

“…The melt curves of a single gene in the different samples showed one single, overlapping peak, and the amplification efficiency of each of the target genes and the housekeeping gene were all similar and within a span of 0.9 and 1.1 (shown in Table 2). The relative gene expression levels were determined using Step-One software (Applied Bio-systems) and were calculated relative to the same gene in the duodenum of the NBW piglets using the 2 − CT method (Dong et al, 2014;Livak and Schmittgen, 2001).…”

“…years (Widdowson, 1971;Cailhol et al, 2009;Wang et al, 2008;Neumann et al, 1998;Dong et al, 2014;Zhong et al, 2012a) A study has reported that IUGR is associated with lower numbers of T regs (CD3 + , CD4 + , CD25 high , and FoxP3 high ) and fewer functional T regs compared to term-appropriate-weight infants (Mukhopadhyay et al, 2014), and a low maternal CD4 percentage has been reported to be independently associated with IUGR (Cailhol et al, 2009). T lymphocytes are believed to be the main regulators of the mucosal immune response.…”