Intrauterine growth retarded piglet as a model for humans – Studies on the perinatal development of the gut structure and function

Ferenc, Karolina; Pietrzak, Piotr; Godlewski, M; Piwowarski, Jan; Kiliańczyk, R.; Guilloteau, Paul; Zabielski, R.

doi:10.1016/j.repbio.2014.01.005

Cited by 82 publications

(77 citation statements)

References 78 publications

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“…Individuals displaying IUGR syndrome, due to modification of their energy metabolism in the foetal period and onward, develop metabolic diseases (such as obesity, hyperlipidemia, insulin resistance, and cardiovascular diseases) with much higher probability than the non-IUGR individuals [17]. The problem is serious, also in humans, since it concerns 6–8% of human population [18].…”

Section: Discussionmentioning

confidence: 99%

Structure and Function of Enterocyte in Intrauterine Growth Retarded Pig Neonates

et al. 2017

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The intestine of intrauterine growth retarded (IUGR) neonates showed different morphology compared to neonates born with normal body weight (NBW). The aim of the present study was to investigate the ultrastructure and proteomic profile of the gut epithelium in IUGR pig neonates with special attention to the digestive and absorptive function. Intestine tissue samples were investigated in 7-day-old IUGR and NBW littermate piglets using histometry, immunofluorescence, scanning electron microscopy (SEM), and mass spectrometry analysis. IUGR piglets have shown reduced mucosa and muscularis thickness and an enhanced number of foetal type enterocytes (FTE). SEM studies have shown the lack of the characteristic large-size vacuole in IUGR's enterocytes. Delayed removal of FTE in IUGR neonates was probably due to the inhibited apoptosis in the apical part of villi and increased apoptosis and reduced mitosis in the crypt region. In the expression of proteins in the intestinal mucosa such as hexokinase I, histones, and prelamin A/C, carbamoyl phosphate was reduced in IUGR neonates. Finally, IUGR intestines showed higher expression of HSPA9 and HSPA5 as apoptosis markers. The data indicate modifications of gut mucosa in IUGRs that may result in slower gut mucosa maturation and reduced utilisation of nutrient as compared to NBW pig neonates.

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Section: Discussionmentioning

confidence: 99%

Structure and Function of Enterocyte in Intrauterine Growth Retarded Pig Neonates

et al. 2017

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“…The neonatal pig was used as a model for the human infant due to their similar anatomy, metabolism, and rapid growth rates in the neonatal period (Bauer et al, 2003; Ferenc et al, 2014). In addition, a comparison of LBWT and NBWT pigs from the same litter reduces possible variation due to confounding parental influence.…”

Section: Discussionmentioning

confidence: 99%

“…Pigs exhibit the highest rate of LBWT (up to 20% of the litter) than any other domestic mammals, and develop LBWT spontaneously without any maternal nutrient or experimental interventions (Wu et al, 2006). The piglet serves as an infant model of LBWT due to metabolic and physiologic similarities with humans (Ferenc et al, 2014). More importantly, naturally occurring LBWT in pigs is characterized by asymmetric growth, the most prevalent feature (75%) in LBWT human infants (Bauer et al, 2003; Ferenc et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…The piglet serves as an infant model of LBWT due to metabolic and physiologic similarities with humans (Ferenc et al, 2014). More importantly, naturally occurring LBWT in pigs is characterized by asymmetric growth, the most prevalent feature (75%) in LBWT human infants (Bauer et al, 2003; Ferenc et al, 2014). A hallmark of asymmetric growth is the disproportionate slow growth of muscles compared to vital organs, such as the brain which is generally unaffected (Bauer et al, 2003; Rehfeldt and Kuhn, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Downregulated Translation Initiation Signaling Predisposes Low-Birth-Weight Neonatal Pigs to Slower Rates of Muscle Protein Synthesis

et al. 2017

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Low-birth-weight (LBWT) neonates experience restricted muscle growth in their perinatal life. Our aim was to investigate the mechanisms that contribute to slower skeletal muscle growth of LBWT neonatal pigs. Twenty-four 1-day old male LBWT (816 ± 55 g) and normal-birth-weight (NBWT; 1,642 ± 55 g) littermates (n = 12) were euthanized to collect blood and longissimus dorsi (LD) muscle subsamples. Plasma glucose, insulin, and insulin-like growth factor-I (IGF-I) were lower in LBWT compared with NBWT pigs. Muscle IGF-I mRNA expression were lower in LBWT than NBWT pigs. However, IGF-I receptor mRNA and protein abundance was greater in LD of LBWT pigs. Abundance of myostatin and its receptors, and abundance and phosphorylation of smad3 were lower in LBWT LD by comparison with NBWT LD. Abundance of eukaryotic initiation factor (eIF) 4E binding protein 1 and mitogen-activated protein kinase-interacting kinases was lower in muscle of LBWT pigs compared with NBWT siblings, while eIF4E abundance and phosphorylation did not differ between the two groups. Furthermore, phosphorylation of ribosomal protein S6 kinase 1 (S6K1) was less in LBWT muscle, possibly due to lower eIF3e abundance. In addition, abundance and phosphorylation of eIF4G was reduced in LBWT pigs by comparison with NBWT littermates, suggesting translation initiation complex formation is compromised in muscle of LBWT pigs. In conclusion, diminished S6K1 activation and translation initiation signaling are likely the major contributors to impaired muscle growth in LBWT neonatal pigs. The upregulated IGF-I R expression and downregulated myostatin signaling seem to be compensatory responses for the reduction in protein synthesis signaling.

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“…We established a pig model of IUGR according to the standard that piglets were at least 1.5 SD lower birth weight compared to their NBW littermates (Che et al 2010). Contrast with the rodent model (Reamon-Buettner et al 2014), pig could be a better animal model to study IUGR because of its high similarities in body metabolism and function, as well as prenatal and postnatal development of the gastrointestinal tract with humans (Ferenc et al 2014; Jiang and Sangild 2014). RRBS, a genome-scale, relatively low-cost method for pig DNA methylome analysis, was applied to study the DNA methylation changes in the jejunum tissues of IUGR piglets.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide DNA methylation analysis in jejunum of Sus scrofa with intrauterine growth restriction

Gong

et al. 2018

Mol Genet Genomics

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Intrauterine growth restriction (IUGR) may elicit a series of postnatal body developmental and metabolic diseases due to their impaired growth and development in the mammalian embryo/fetus during pregnancy. In the present study, we hypothesized that IUGR may lead to abnormally regulated DNA methylation in the intestine, causing intestinal dysfunctions. We applied reduced representation bisulfite sequencing (RRBS) technology to study the jejunum tissues from four newborn IUGR piglets and their normal body weight (NBW) littermates. The results revealed extensively regional DNA methylation changes between IUGR/NBW pairs from different gilts, affecting dozens of genes. Hiseq-based bisulfite sequencing PCR (Hiseq-BSP) was used for validations of 19 genes with epigenetic abnormality, confirming three genes (AIFM1, MTMR1, and TWIST2) in extra samples. Furthermore, integrated analysis of these 19 genes with proteome data indicated that there were three main genes (BCAP31, IRAK1, and AIFM1) interacting with important immunity- or metabolism-related proteins, which could explain the potential intestinal dysfunctions of IUGR piglets. We conclude that IUGR can lead to disparate DNA methylation in the intestine and these changes may affect several important biological processes such as cell apoptosis, cell differentiation, and immunity, which provides more clues linking IUGR and its long-term complications.Electronic supplementary materialThe online version of this article (10.1007/s00438-018-1422-9) contains supplementary material, which is available to authorized users.

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Intrauterine growth retarded piglet as a model for humans – Studies on the perinatal development of the gut structure and function

Cited by 82 publications

References 78 publications

Structure and Function of Enterocyte in Intrauterine Growth Retarded Pig Neonates

Structure and Function of Enterocyte in Intrauterine Growth Retarded Pig Neonates

Downregulated Translation Initiation Signaling Predisposes Low-Birth-Weight Neonatal Pigs to Slower Rates of Muscle Protein Synthesis

Genome-wide DNA methylation analysis in jejunum of Sus scrofa with intrauterine growth restriction

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