Projects

Abstract

Intrauterine growth restriction (IUGR) describes a pathological condition in which the fetus fails to grow to its biological potential, primarily because of poor placental function. IUGR affects 8% of pregnancies in high-income countries, and is a leading cause of perinatal mortality and morbidity. IUGR can cause neurological deficiencies, however the mechanisms underlying these deficiencies remain to be determined. With the wide range of neurodevelopmental disorders associated with IUGR, the use of animal models appropriate to investigating mechanisms of injury in the IUGR newborn is crucial for the development of effective and targeted therapies for babies. The perinatal development of the central nervous system in pigs is very similar to that in humans. Piglets are therefore considered a solid model to explore how perinatal insults affect brain structure and function. This project aims to look for proteins in the hippocampus with important roles in the neuronal development and function where sex differences in IUGR have been described earlier in order to explain the better adaptation of female IUGR piglets compared to male piglets. The importance to map the morphological differences in the hippocampus can help us to understand the pathophysiology of neurodevelopmental disorders later in life. This is important because new insights into the pathophysiology can lead to novel therapeutic or preventive therapies against IUGR.

Researcher(s)

• Promoter: Van Bockstal Lieselotte

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

The central objective of this project is to demonstrate that early-life stress is a risk factor for the development of gastrointestinal dysfunction and that males and females differ in how they cope with early-life stress. This differing response is believed to be present already in utero, whereby it is suggested that the male offspring is disadvantaged in responding to stressors during pregnancy. However, during postnatal development, the female appears to be the weaker sex when it comes to the development of a leaky gut and a dysfunctional gastrointestinal tract. In this project, we want the study sex-related differences in intestinal permeability during the period when the gastrointestinal tract undergoes extensive developmental changes. During this window of plasticity, stressors can disrupt the normal developmental process, having long-lasting effects on the gut. Therefore, we will include early life stress during late gestation (intrauterine growth restriction) or during the juvenile phase (chronic stress during artificial rearing) in our set-up to research whether males and females mount a differing response. This will be done in a newborn and juvenile piglet.

Researcher(s)

• Promoter: Van Ginneken Chris
• Co-promoter: Van Bockstal Lieselotte
• Fellow: Banous Naya
• Fellow: Mohaghegh Toosi Ali

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Flemish pig farms face a number of important techno-economic challenges: high perinatal mortality, challenge to rear increasingly large and heterogeneous litters, decline in performance around weaning with increased susceptibility to infections, prophylactic antibiotic use, etc. These techno-economic problems affect animal welfare and often present the pig farmer with the choice of keeping an animal alive or not (e.g. weak piglets in the farrowing pen). Notwithstanding that the legislator provides a framework regarding the killing of animals/pigs, elaborating a transparent policy at sector level is difficult. Moreover, due to fears of public opinion, pig farmers are very reluctant to communicate a policy on the killing of sick and weak piglets - and on the extension of older age classes of pigs. The outcomes of this project are a decision tree, an educational package and competency assessment that will be developed with input from the different stakeholders.

Researcher(s)

• Promoter: Van Ginneken Chris

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

The current high-throughput multi-omics technologies, complemented with revolutionary micro- and nanoscopic imaging tools, offer amazing opportunities for holistic investigation and pathophysiologic understanding of diseases in both man and animals. However, the accurate and specific quantification of small organic molecules currently faces two major challenges: 1) the increasing availability of microsamples from biological origin having ever smaller sizes requires the increasing need for ultrasensitive quantification up to sub-pg/g (mL) level; 2) the unmet need for imaging and spatial distribution mapping of these small molecules in complex biological matrices. The proposed modular and nanoscale ultra-high performance liquid-chromatography tandem mass spectrometer holds the unique features to simultaneously fill both gaps in the current multi-omics workflow. We target the analysis of drugs, toxins and endogenous compounds, as well as their metabolites and biomarkers in in vitro and in vivo samples of human and animal origin. This unique instrument is currently not available in Belgium and will be embedded as shared facility within the UGent MSsmall Expertise Centre, established in 2017 with the ambition to support high quality life science research with state-of-the-art mass spectrometry equipment and expertise. Broad interest in this high-end technology is evidenced by the support of 23 promoters from several (bio)medical faculties of 3 Flemish universities.

Researcher(s)

• Promoter: Van Cruchten Steven

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Prof. Sangild will give a series of 4 lectures on his research that he will present under the heading of 'survival of weak newborns - a cross-species science." The lectures will be partly in person, partly online. They are organised between 26th April 2022 and 16th May 2022.

Researcher(s)

• Promoter: Van Ginneken Chris

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Within Europe, alternative methods for toxicity assessment of xenobiotics become very important. Several pharmaceutical, agrochemical and cosmetic companies are currently using the zebrafish embryo as an alternative for animal testing to screen new compounds for developmental toxicity. However, false negative and false positive results are reported in the Zebrafish Embryo Developmental Toxicity Assay (ZEDTA) for known mammalian teratogens and non-teratogens, respectively. For safety, false negative results are more critical, as teratogens may be missed. This project aims to further refine the ZEDTA in order to increase the sensitivity of the assay and as such better predict birth defects caused by using drugs during the 1st trimester of pregnancy. In order to achieve this goal, first the number of evaluated morphological endpoints will be extended by including skeletal staining in the ZEDTA. Second, due to the intrinsically low biotransformation capacity of zebrafish embryos, a metabolic activation system will be developed in order to expose the zebrafish embryos not only to the parent compound but also to its potential teratogenic metabolite(s). Finally, additional morphological endpoints will be programmed in image analysis software that will be combined with an automated handling and imaging system. As such, this project will increase the sensitivity and throughput of the ZEDTA, resulting in better, faster and laboratory animal-free screening of teratogenic drugs.

Researcher(s)

• Promoter: Van Cruchten Steven
• Co-promoter: Foubert Kenn
• Fellow: Hoyberghs Jente

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project website

Project type(s)

• Research Project

Abstract

Single stranded oligonucleotides (SSOs) are a new class of drugs that are used to inhibit the expression of specific proteins by hybridizing to specific mRNAs, e.g. in cancer cells. For adult indications, non-human primates (NHPs) are often considered to be the non-rodent species of choice for the safety assessment of SSOs, but recently the Göttingen minipig has been proven to be a good alternative. This animal model also has several ethical and practical advantages over NHPs for pediatric safety testing of SSOs, but the juvenile Göttingen minipig has not yet been characterized for this purpose. In the adult population, SSOs distribute from the circulation into tissues within minutes to a few hours after systemic administration. The aim of this project is to investigate these processes in juvenile Göttingen minipigs. These data will be very useful for the interpretation of pediatric safety data with new SSOs.

Researcher(s)

• Promoter: Van Cruchten Steven
• Fellow: Valenzuela Allan

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Drug disposition in neonates depends on maturational and non-maturational covariates. We hypothesize that cooling, a standard therapy for asphyxiated neonates with hypoxic-ischemic encephalopathy, is such a non-maturational covariate. The main goal of the project is to develop an innovative physiology-based pharmacokinetic (PBPK) framework to describe and predict the impact of cooling on drug disposition in asphyxiated neonates. PBPK models combine drug-specific data with physiological data of a population of interest to guide drug dosing. The effect of cooling on drug metabolism is hereby defined as a knowledge gap. Using a multidisciplinary approach, in vitro, animal experimental and human data will be collected for development of the model. First, the impact of temperature on expression and function of drug metabolizing enzymes (DME) and drug transporters (DT) will be assessed in vitro on human and porcine hepatocytes. Second, the utility of endogenous biomarkers reflecting DME and DT activity during cooling is investigated. Third, the results will be used to build PBPK models for selected drugs. Finally, in vivo PK data in human asphyxiated neonates undergoing cooling and in an experimental in vivo setting of neonatal minipigs will be used to evaluate the models. The outcome will be drug dose prediction and drug development in neonates undergoing cooling. The framework may also be applied to develop temperature driven PBPK-models in other special populations.

Researcher(s)

• Promoter: Van Cruchten Steven

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Within Europe, alternative methods for toxicity assessment of xenobiotics become very important. Several pharmaceutical, agrochemical and cosmetic companies are currently using the zebrafish embryo as an alternative for animal testing to screen new compounds for developmental toxicity. However, false negative and false positive results are reported in the Zebrafish Embryo Developmental Toxicity Assay (ZEDTA) for known mammalian teratogens and non-teratogens, respectively. From a safety point of view, false negative results are more critical because teratogens may be missed by the assay. This project aims to further refine the ZEDTA protocol in order to increase the sensitivity of the assay and to advance the ZEDTA from screening towards potential regulatory acceptance. In order to achieve this goal, first the number of evaluated morphological endpoints will be extended by including skeletal staining in the ZEDTA. Second, due to the intrinsically low biotransformation capacity of zebrafish embryos, a metabolic activation system will be developed in order to expose the zebrafish embryos not only to the parent compound but also to its potential teratogenic metabolite(s). Finally, additional morphological endpoints will be programmed in image analysis software that will be combined with an automated handling and imaging system. As such, this project will increase the sensitivity and throughput of the ZEDTA for potential regulatory use.

Researcher(s)

• Promoter: Van Cruchten Steven
• Co-promoter: Foubert Kenn
• Fellow: Hoyberghs Jente

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Histological sections of the different intestinal samples will be stained histochemically and using image analysis villus length, crypt depth, crypt width and the number of goblet cells will be determined. Pictures will be taken from the different regions. All data will be analyzed in UGent.

Researcher(s)

• Promoter: Van Ginneken Chris

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

The number of morphological endpoints in the ZEDTA is much more limited compared to the in vivo developmental toxicity studies. A survey within the laboratories of the proposers pointed out that especially the skeletal endpoints are limited in the ZEDTA. A literature review showed false negative results in the ZEDTA for compounds that showed skeletal abnormalities in mammalian studies. The aim of this project is to assess whether extension of the morphological parameters and evaluation period in the ZEDTA after exposure to mammalian skeletal teratogens during organogenesis increases the concordance of the ZEDTA with the mammalian in vivo developmental toxicity studies.

Researcher(s)

• Promoter: Van Cruchten Steven

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Within Europe, alternative methods for toxicity assessment of xenobiotics become very important. For developmental toxicity, the mouse Embryonic Stem Cell test and the rat Whole Embryo Culture are commonly used, but assays in non-mammalian whole organisms are currently proposed as they more fully represent the complexity of early development. The zebrafish (Danio rerio) is one of the preferred species due to their small size, high fecundity and rapid ex utero development. However, knowledge on the ontogeny of biotransformation enzymes in this species remains scarce. This is a pivotal information, especially for proteratogens that require bioactivation to exert their teratogenic potential. The cytochrome P450 enzymes (CYPs) represent the most important enzyme family in this oxidative process and are also important for the (de) activation of endogenous molecules that regulate normal embryonic development. The aim of this research project is to assess the bioactivation capacity of zebrafish embryos by using molecular techniques that target specific CYP isoenzymes. As such, this project will show whether zebrafish embryos can bioactivate, and thus detect, proteratogens or not, which is key information when considering this alternative assay for developmental toxicity testing.

Researcher(s)

• Promoter: Van Cruchten Steven
• Co-promoter: Foubert Kenn
• Co-promoter: Labro Alain
• Fellow: Bars Chloe

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

The modern Flemish pig breeding farms face important technical and economic challenges: perinatal piglet mortality is high, rearing the increasing numbers of large litters (>20 piglets/litter) is a major challenge, and the abrupt weaning of pigs causes a decline in performance and an increase in the susceptibility to infections. Consistent with these problems, there is an extremely high prophylactic antibiotic use. Together with the pork industry, we want to give impetus to address these challenges. This project aims to introduce and optimize innovative concepts in piglet rearing in order to raise more resilient piglets in a profitable way. 'Resilience' is defined as the ability of the animal to restore its homeostasis if it is disturbed under normal physiological conditions. The innovative concepts we will optimize and introduce in the pig breeding farms are: 1 / interventions at the neonatal big: split-suckling, drenching of bioactive substances, and 2 / interventions to prepare for the process of weaning: multi-suckling with foraging. Split-suckling involves splitting up the litter into smaller groups which alternately get the chance to suckle colostrum and milk. Up to now there is much discussion on which criteria are best used for making the groups and what the optimal timing of the suckling periods is. Bioactive substances (antioxidants, bovine colostrum or whey protein concentrates, and oligosaccharides) can be administered via booster preparations, or enclosed in artificial milk and creep feed. Which bioactive substances will result in more resilient pigs in a profitable way is the main focus of this UAntwerpen PhD. The concept of multi-suckling involves opening the farrowing crates at a certain age of the piglets. This allows the piglets to interact and to suckle also other sows in order to maximize feed intake. The different rearing strategies that will be optimized in this project are relatively easy to implement in existing breeding systems in Flanders and do not require large investments. Nevertheless, we want to optimize the knowledge on the effects on performance, resilience of these concepts and make an inventory of the labor costs these concepts request. Knowing the effects (short and long term) on performance and resilience will facilitate introducing the concepts into the pig farms and reduce the prophylactic use of antimicrobials.

Researcher(s)

• Promoter: Van Ginneken Chris

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Underdevelopment of the gastrointestinal tract (GIT) in humans is observed in intrauterine growth restricted (IUGR) and preterm newborns and this differential development may have important implications for future health. The mechanism that drives these differences needs further investigation that must be carried out in animals. The pig being a reliable model for GIT studies and thus the molecular approach presented in this proposal can bring new insights into the genes and pathways involved in the GIT development from the late prenatal to weaning periods in normal and IUGR piglets. The outcome of this project could highlight differences in transcription patterns between these conditions and/or age groups. Moreover, genes that show differential expression between normal and IUGR piglets will be further examined to determine whether these changes can be inherited by the offspring (i.e. due to epigenetic modulation).

Researcher(s)

• Promoter: Ayuso Hernando Miriam

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Within Europe, alternative in vitro methods for toxicity assessment of xenobiotics become very important. For developmental toxicity, the mouse Embryonic Stem Cell test and the rat Whole Embryo Culture are commonly used, but assays in non-mammalian species, as a whole organism, are currently proposed as they more fully represent the complexity of early development. The zebrafish (Danio rerio) is one of the preferred species due to their small size, high fecundity and rapid ex utero development. However, knowledge on the ontogeny of biotransformation enzymes in this species remains scarce. This is pivotal information, especially for proteratogens that require bioactivation to exert their teratogenic potential. The cytochrome P450 enzymes (CYPs) represent the most important enzyme family in this oxidative process and are also important for the (de)activation of endogenous molecules that regulate normal embryonic development. The identification and developmental expression of CYP genes in the zebrafish have been reported but the translation to functional enzymes, i.e. activity of the CYPs, remains to be elucidated despite attempts of several research groups. Indeed, very low CYP1A activity has been detected in microsomes from whole embryo homogenates but whether the in vivo tissue-specific concentration of these metabolites is insufficient to cause a teratogenic effect, could not be concluded. The ultimate proof of the bioactivation capacity of zebrafish embryos is the presence of malformations after exposure of zebrafish embryos to known proteratogens. However, in that particular scenario one needs to be sure that only the metabolite(s) of the prodrug is teratogenic and not the compound itself. Therefore, the aim of this research project is to assess the bioactivation capacity of zebrafish embryos by using molecular techniques that target specific CYP isoenzymes. In that way the role of these CYPs in normal embryonic development and their function in bioactivation of proteratogens will be unraveled.

Researcher(s)

• Promoter: Van Cruchten Steven

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

During drug development, pharmaceutical companies are required to characterize all routes of clearance (drug elimination) in man. Although the characterization of the metabolic profile of a drug is only required prior to the start of Phase 3 clinical trials, earlier information is very useful for the species selection in safety studies. Therefore, in vitro drug metabolism studies in several species are often performed early during drug development. Liver microsomes or the S9 fraction are the most common tools for screening of effects of a new drug on the CYP450 pathways, although liver slices or isolated hepatocytes give a more complete picture. To unravel the specific isoenzymes involved in the metabolism of drugs, recombinantly expressed cDNA of several CYP isoforms is used and commercially available for a number of species, including man, mouse, rat, dog and monkey. For the minipig no recombinant CYPs are commercially available. This species is, however, increasingly used in juvenile and general toxicity studies. Therefore, the aim of our project is to develop recombinant CYP enzymes of the minipig and compare their activity with adult minipig liver microsomes and in vivo pharmacokinetic (PK) data. This minipig recombinant system can be very valuable for pharmaceutical companies for species selection in non-clinical studies.

Researcher(s)

• Promoter: Van Cruchten Steven
• Co-promoter: Labro Alain

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

The zebrafish is increasingly used for toxicological purposes. However, knowledge on the biotransformation processes in this species is scarce, especially in zebrafish embryos which are increasingly used as an alternative model for teratogenicity screening of pharmaceuticals. In this project, we will assess the intrinsic activity of cytochrome P450 (CYPs) in adult male and female zebrafish and during embryonic development. This project will provide information on possible gender differences in CYP activity in the adult zebrafish and also on the capacity of zebrafish embryos to metabolize xenobiotics.

Researcher(s)

• Promoter: Van Cruchten Steven
• Fellow: Saad Moayad

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

The zebrafish embryo is already being used for teratogenicity testing, i.e. in the Zebrafish Developmental Toxicity Assay (ZEDTA). However, in vitro data of our research group and in vivo data from other labs indicate that the zebrafish embryo shows no or low bioactivity. As such proteratogens, i.e. compounds that require bioactivation to exert their teratogenic potential, may be missed in the ZEDTA and lead to false negative results. Currently, rat exogenous metabolic activation system (MAS) is used to optimize the ZEDTA but it is controversial as it causes embryotoxicity by itself and its metabolic profile may be different than in man. The temperature of the co-incubation system may contribute to the observed embryotoxicity. Zebrafish embryos develop optimally between 26,5-28,5°C and do not tolerate the physiological temperature of rat MAS (38-39°C). Therefore, 32°C is often used in the coincubation system as a compromise. However, very recently we assessed temperature effects on zebrafish embryonic development and observed that 32,5°C causes embryotoxicty. Therefore, the aim of this research project is to develop a novel coincubation system (MAS) that functions at a non-embryotoxic temperature. Instead of rat MAS, we will evaluate in a first phase the bioactivity and embryotoxicity of human MAS (to obtain a human relevant metabolic profile) at different temperatures and of zebrafish MAS at 28,5°C (physiological condition for embryonic development). Regarding bioactivity, we will focus on xenobiotic metabolizing CYP families (i.e. CYP 1-3) and limit ourselves to fluorogenic substrates that are relevant to man and covering approx. 95% of human xenobiotic metabolism. Metabolite concentrations will be determined in the supernatans over-time by detection of the fluorescent signal. In a second phase we will evaluate biotransformation in the ZEDTA in presence and absence (controls) of hMAS and zMAS. This will be achieved by exposing early zebrafish embryos to the same substrates of the first phase. For the co-incubation, we will select the optimal temperature from the first phase. Metabolite concentrations will be determined over-time in the embryo and in the supernatans by detection of the fluorescent signal.

Researcher(s)

• Promoter: Van Cruchten Steven
• Co-promoter: Knapen Dries
• Fellow: Pype Casper

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project website

Project type(s)

• Research Project

Abstract

The main objective of this research project is to assess whether differences in saliva proteome exist between LBW and NBW piglets that have been differently reared, i.e. conventional weaning at the age of 28 days or unconventional artificial rearing on milk formula from three days of age until the conventional weaning age.

Researcher(s)

• Promoter: Casteleyn Christophe

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Zebrafish (Danio rerio) are commonly used in drug development because of its advantages. As zebrafish are small, only little compound is needed compared to mammals. Furthermore, the expenses for the maintenance of the fish stock are limited and the fish show a high fecundity throughout the year. Moreover, the externally fertilised eggs develop in a similar way as higher vertebrate species, including humans. Because of these advantages, zebrafish are nowadays being used for screening new drugs for their teratogenic potential in the Zebrafish Teratogenicity Test (ZTT). However, optimal study conditions aren't available, indicating the need for further optimalisation of the test before it can be used as a valid screening model. Therefore, we will investigate the use of human- and zebrafish-derived liver microsomes in order to optimize the biotransformation of compounds.

Researcher(s)

• Promoter: Van Cruchten Steven
• Co-promoter: Knapen Dries
• Fellow: Pype Casper

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Low birth weight piglets represent an important economic loss for the pig farmer. These piglets show high mortality and morbidity, growth retardation, higher slaughter age, poor meat quality and more stress, which affects animal welfare. This project aims to elucidate the differences between the low and normal birth weight piglet regarding the development and maturation of the immune system, in particular the gut-associated lymphoid tissue (GALT). In addition, the effects of early weaning and further raising with formulated milk on the immune system of the piglet, in particular the low birth weight piglet, will be investigated. The applied methodology to achieve the research goals includes morphometry of the GALT, determination of the occurrence and number of M cells, assessment of the in vitro functional immunological capacity, and stimulation of the immune system by means of immunomodulating nutrients. The results of this project can add value to the evidence-based health management of piglets.

Researcher(s)

• Promoter: Casteleyn Christophe
• Fellow: Prims Sara

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

The aim of this research project is to develop a new exogenous metabolic activation system (MAS) to optimize the biotransformation of the ZET. To achieve this goal we will first evaluate and compare the biotransformation and embryotoxic potential of human MAS with induced zebrafish MAS (izMAS) by exposure to different substrates. We will focus on xenobiotic metabolizing CYP families (i.e. CYP 1-3) and limit ourselves to substrates that are relevant to man and covering approx. 95% of human xenobiotic metabolism. Parent compound and metabolites will be determined in the supernatans over-time by LC-MS.

Researcher(s)

• Promoter: Van Cruchten Steven

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project website

Project type(s)

• Research Project

Abstract

Introducing hyperprolific hybrid sows in pork production has resulted in large litters that contain up to 20% low birth weight (LBW) piglets. As these piglets are more susceptible to disease than normal birth weight (NBW) piglets, the litter is often weaned early and subsequently fed with formulated milk (formula). Although this strategy allows LBW piglets to catch up growth, their morbidity and mortality do not decrease. This could be due to the fact that formula is low in bioactive molecules (e.g. growth factors, hormones and cytokines), necessary for the development of the immune system. The proposed research project will determine the influences of birth weight, age and milk composition on the development of the gut-associated lymphoid tissue (GALT) of the neonatal piglet. To this purpose, LBW and NBW piglets will be pre-weaned at the age of 3 days, and subsequently be fed ad libitum for 7 or 25 days with either formula or formula supplemented with a whey fraction. Control animals suckle the sow. After euthanasia of the animals at day 10 or 28, samples of the ileum will be processed for quantitative, stereological analysis of various immune cell populations. The obtained results will be valuable in gaining insight into the development of the GALT of the neonatal piglet. This is a prerequisite for further research on vaccination strategies and feeding regimens to obtain immunocompetent piglets that are less susceptible to disease.

Researcher(s)

• Promoter: Casteleyn Christophe

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand EU. UA provides EU research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Van Cruchten Steven
• Co-promoter: Cos Paul

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Drug transporters and metabolizing enzymes play a pivotal role in the pharmacokinetics of most drugs. The ATP-binding cassette (ABC) drug efflux transporters and cytochrome P450 isoenzymes (CYP) are the best known of these two groups, respectively, but numerous other subgroups are involved in the absorption, distribution, metabolism and elimination of drugs. The presence and activity of these systems in hepatocytes and enterocytes influence oral bioavailability and as such they may determine the clinical efficacy but also the toxicity of orally ingested drugs. Although many of these pharmaceuticals are also used in (very young) children and differences in oral bioavailability are common compared to adults, studies on the ontogeny of drug transporters and metabolizing enzymes are scarce. This information is also pivotal in juvenile animals as, from a safety perspective, toxicity studies in one or more species may be required prior to the start of clinical trials in children. Knowledge on the ontogeny of these enzymes and transporters in different organ systems is building up in the rat, but in non-rodent species data are lacking. As the minipig is the most commonly used non-rodent species in juvenile toxicity studies besides the dog, information on the ontogeny of drug efflux transporters and metabolizing enzymes is pivotal in the interpretation of these studies. Therefore, the aim of this project is to verify the gene expression levels of different drug transporters and metabolizing enzymes in the liver and small intestine of fetal, neonatal, suckling and weanling minipigs in order to cover a pediatric population of < 2 years of age.

Researcher(s)

• Promoter: Van Cruchten Steven

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Van Ginneken Chris

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Intrauterine growth retardation (IUGR) impairs gut growth. This study examines the relation between IUGR and a possibly compromised enteric nervous system. The latter could contribute to the lower growth rates observed in IUGR.

Researcher(s)

• Promoter: Van Ginneken Chris

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Approximately 10% of the low birth weight infants develop necrotizing enterocolitis (NEC). Symptoms of NEC such as abnormal intestinal motility, permeability and blood flow can be linked to a neuropathy of the enteric nervous system (ENS). In the preterm piglet and neonatal rat, in vivo and in vitro experiments will be used to challenge the hypothesis that a neuropathy of the ENS plays a role in the ethiopathogenesis of NEC.

Researcher(s)

• Promoter: Van Ginneken Chris

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Optimizing growth and health during the suckling period of piglets with impaired growth is an economic challenge and relevant for improving animal welfare. This projects investigates which subfractions of immunoglobulin-free bovine colostral whey could promote growth and health in suckling piglets by studying key-structures and functions in the small intestine both in vivo and in vitro at the macro- (nutritional and growth effects) and micro-level (effects on intestinal morphology and physiological parameters).

Researcher(s)

• Promoter: Van Ginneken Chris
• Co-promoter: Dewilde Sylvia
• Co-promoter: Hesta Myriam

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Optimizing growth and health during the suckling period of piglets with impaired growth is an economic and ethical challenge. This projects investigates the immunoglobulin-free fraction of bovine colostral whey and: 1/ describes the effects on macro- (nutritional and growth effects) and micro leve' (relevant morphological and functional gastrointestinal parameters) of bio-active substances present. 2/ points out which parts can be held responsible for the observed effects. 3/ creates a method (model) for estimating the efficacy of food compounds regarding growth in function of the effects on intestinal physiology and morphology

Researcher(s)

• Promoter: Van Ginneken Chris

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Chronic progressive lymphedema in draft horses, closely related to human primary lymphedema, is characterized by significant proliferation of extracellular matrix. The underlying pathogenesis is still unknown. This project will evaluate the role of growth factors, elastase, metalloproteïnases and their inhibitors in the regulation of the extracellular matrix and of the activity of the elastin gene in this disease.

Researcher(s)

• Promoter: De Cock Hilde

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Feeding human milk, when compared with formulated milk, results in a better growth and maturation of the gastrointestinal tract. These beneficial effects can be attributed, at least in part to the unique composition of human milk. Topic of this study will be to investigate to what extent these beneficial effects are mediated by a modulation of the morphology of the enteric nervous system in an in vivo and in vitro pig model.

Researcher(s)

• Promoter: Van Ginneken Chris

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: De Cock Hilde

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: De Cock Hilde

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Necrotizing enterocolitis (NEC) afflicts 7-10% of the premature babies and has a mortality rate of 20-40%. NEC occurs in premature piglets being fed a milk replacer. This project aims to describe the morphology and functional characteristics of this animal model. By manipulating the availability of arginine and NO, we aim to find clues for the cause of NEC.

Researcher(s)

• Promoter: Van Ginneken Chris

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Necrotizing enterocolitis (NEC) afflicts 7-10% of the premature babies and has a mortality rate of 20-40%. NEC occurs in premature piglets being fed a milk replacer. This project aims to describe the morphology and functional characteristics of this animal model. By manipulating the availability of arginine and NO, we aim to find clues for the cause of NEC.

Researcher(s)

• Promoter: Van Ginneken Chris

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Weyns Andre
• Co-promoter: Van Ginneken Chris

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Weyns Andre

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Van Ginneken Chris
• Co-promoter: Weyns Andre

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Van Ginneken Chris

Research team(s)

• Comparative Perinatal Development (CoPeD)

Project type(s)

• Research Project