Rodent models of metabolic disorders: considerations for use in studies of neonatal programming

Epidemiologically, metabolic disorders have garnered much attention, perhaps due to the predominance of obesity. The early postnatal life represents a critical period for programming multifactorial metabolic disorders of adult life. Though, altricial rodents are prime subjects for investigating neonatal programming, there is still no sufficiently generalised literature on their usage and methodology. This review focuses on establishing five approach-based models of neonatal rodents adopted for studying metabolic phenotypes. Here, some modelled interventions that currently exist to avoid or prevent metabolic disorders are also highlighted. We also bring forth recommendations, guidelines, and considerations to aid research on neonatal programming. It is hoped that this provides a background to researchers focused on the aetiology, mechanisms, prevention and treatment of metabolic disorders.

Neonatal programming of piglet gut health and postnatal effects by maternal transfer of phytogenic compounds supplemented in gestating and lactating hyperprolific sows

Background The improvement of sow prolificacy by breeding has increased the number of piglets produced per sow per year. However, intrauterine crowding and/or intrauterine growth restriction typically observed in hyperprolific sows impairs foetal growth which has decreased the average individual birthweight, with a larger proportion of low birthweight (LBW) pigs born per litter with poor gut development and compromised postnatal growth performance. Phytogenic compounds (PC) are plant-derived natural bioactive substances that can be used in livestock production as feed additives to promote animal health and production efficiency. This research aims to study if a specific blend of PC (BPC) supplemented in gestating and lactating hyperprolific sow diets may promote pre- and postnatal maternal effects on performance and oxidative status of sows and their offspring, colostrum-milk features, and piglet gut health-related gene expression and morphology. Forty DanBred hybrid line Landrace x Yorkhire gilts and sows (parities 0–7) were randomly allocated by parity number and body weight into two dietary treatments including unsupplemented Control (n = 20) or Control diets supplemented with 1 g/kg feed of BPC (n = 20) throughout gestation and lactation.Results Several dietary PC from the supplemented BPC were transferred to the placental fluid and milk. The BPC supplementation during gestation enhanced the litter size, antioxidant status, and colostrum protein content of sows. Jejunal histomorphology of neonate piglets, and intestinal-function gene expression related to nutrient transport, antioxidant, innate immune response, and digestion were improved in the BPC group. For both, sows and piglets, plasma antioxidant activity of CAT and SOD enzymes were enhanced. For suckling piglets, jejunal expression of genes related to gut barrier function was improved and piglet weight gain from birth to weaning was enhanced in the BPC group.Conclusions Dietary supplementation of BPC in gestating and lactating diets for hyperprolific sows improves sow’s reproductive performance and colostrum composition, with a significant strength of the antioxidant status of sows and their offspring. The prenatal and postnatal maternal transfer (placental fluid and milk) of BPC to the offspring would influence on the neonatal programming and postnatal of piglet’s gut health, with advantageous effects on piglet’s growth performance.

Enhanced sympathetic nerve activity induced by neonatal colon inflammation induces gastric hypersensitivity and anxiety-like behavior in adult rats

Gastric hypersensitivity (GHS) and anxiety are prevalent in functional dyspepsia patients; their underlying mechanisms remain unknown largely because of lack of availability of live visceral tissues from human subjects. Recently, we demonstrated in a preclinical model that rats subjected to neonatal colon inflammation show increased basal plasma norepinephrine (NE), which contributes to GHS through the upregulation of nerve growth factor (NGF) expression in the gastric fundus. We tested the hypothesis that neonatal colon inflammation increases anxiety-like behavior and sympathetic nervous system activity, which upregulates the expression of NGF to induce GHS in adult life. Chemical sympathectomy, but not adrenalectomy, suppressed the elevated NGF expression in the fundus muscularis externa and GHS. The measurement of heart rate variability showed a significant increase in the low frequency-to-high frequency ratio in GHS vs. the control rats. Stimulus-evoked release of NE from the fundus muscularis externa strips was significantly greater in GHS than in the control rats. Tyrosine hydroxylase expression was increased in the celiac ganglia of the GHS vs. the control rats. We found an increase in trait but not stress-induced anxiety-like behavior in GHS rats in an elevated plus maze. We concluded that neonatal programming triggered by colon inflammation upregulates tyrosine hydroxylase in the celiac ganglia, which upregulates the release of NE in the gastric fundus muscularis externa. The increase of NE release from the sympathetic nerve terminals concentration dependently upregulates NGF, which proportionately increases the visceromotor response to gastric distention. Neonatal programming concurrently increases anxiety-like behavior in GHS rats.

Potential of the application of epigenetics in animal production

Our many current environmental challenges, including worldwide abnormal weather, global warming, and pollution, necessitate a new and innovative strategy for animal production for the next generation. This strategy should incorporate not only higher-efficiency production, but also advanced biological concepts and multi-functional agricultural techniques, into environmentally friendly systems. Recent research has discovered a unique phenomenon referred to as ‘foetal and neonatal programming’, which is based on ‘the developmental origins of health and disease (DOHaD)’ concept. These studies have shown that alterations in foetal and early postnatal nutrition and endocrine status may result in developmental adaptations that permanently change the structure, physiology and metabolism of affected animals during adult life. Ruminants fill an important ecological niche that capitalises on the symbiotic relationship between fibre-fermenting ruminal microbes and the mammalian demand for usable nutrients. The timing of the perturbation in maternal nutrient availability plays an important role in determining the effect that the foetal and neonatal programming will have on the developing placenta or foetus and offspring performance. Developmental programming through nutritional manipulations may help the ruminant, as an effective grass–protein converter, fulfil its production potential.