Managing Gut Microbiota through In Ovo Nutrition Influences Early-Life Programming in Broiler Chickens

The chicken gut is the habitat to trillions of microorganisms that affect physiological functions and immune status through metabolic activities and host interaction. Gut microbiota research previously focused on inflammation; however, it is now clear that these microbial communities play an essential role in maintaining normal homeostatic conditions by regulating the immune system. In addition, the microbiota helps reduce and prevent pathogen colonization of the gut via the mechanism of competitive exclusion and the synthesis of bactericidal molecules. Under commercial conditions, newly hatched chicks have access to feed after 36–72 h of hatching due to the hatch window and routine hatchery practices. This delay adversely affects the potential inoculation of the healthy microbiota and impairs the development and maturation of muscle, the immune system, and the gastrointestinal tract (GIT). Modulating the gut microbiota has been proposed as a potential strategy for improving host health and productivity and avoiding undesirable effects on gut health and the immune system. Using early-life programming via in ovo stimulation with probiotics and prebiotics, it may be possible to avoid selected metabolic disorders, poor immunity, and pathogen resistance, which the broiler industry now faces due to commercial hatching and selection pressures imposed by an increasingly demanding market.

163 DNA Methylation Across Generation in Bovine

Scientists are starting to realize that some effects from the animal environment may affect their progeny’s phenotype. These epidemiological evidences of early life programming are very well described in humans and rodents but less documented in bovines, especially in relation to the peri-conceptual period. In fact, as other species the bovine gametes may carry non-genetic information that will impact the survival, the fitness and the phenotype of the embryo-fetus-offspring. Using a peri-pubertal age model we have compared the semen of bulls that we obtained at different ages just after puberty for whole genome DNA methylation, miRNA content and open DNA access regions to identify mechanistic relation to gene expression and DNA methylation in embryos created with the same bulls compared to themselves and mated by IVF to the same heifer several times. A similar experiment was also done with pre-peri and post puber heifers using the same adult bull for repetitive IVF. The overall results indicate that the same pathways are affected in embryos from immature parents. The targeted processes are overwhelmingly associated with cellular metabolism involving mitochondria function and the mTOR pathways amongst others. A very similar conclusion was also observed with embryos obtained from adult mothers under negative energy balance and the resulting calves obtained by surrogate gestations using blood DNA methylation to assess the intergenerational legacy. These results support a metabolic programming across generation associated with an energy deficient status of the parent.

Prenatal and Early Postnatal Behavioural Programming in Laying Hens, With Possible Implications for the Development of Injurious Pecking

Injurious pecking (IP) represents a serious concern for the welfare of laying hens (Gallus gallus domesticus). The risk of IP among hens with intact beaks in cage-free housing prompts a need for solutions based on an understanding of underlying mechanisms. In this review, we explore how behavioural programming via prenatal and early postnatal environmental conditions could influence the development of IP in laying hens. The possible roles of early life adversity and mismatch between early life programming and subsequent environmental conditions are considered. We review the role of maternal stress, egg conditions, incubation settings (temperature, light, sound, odour) and chick brooding conditions on behavioural programming that could be linked to IP. Brain and behavioural development can be programmed by prenatal and postnatal environmental conditions, which if suboptimal could lead to a tendency to develop IP later in life, as we illustrate with a Jenga tower that could fall over if not built solidly. If so, steps taken to optimise the environmental conditions of previous generations and incubation conditions, reduce stress around hatching, and guide the early learning of chicks will aid in prevention of IP in commercial laying hen flocks.

Germline activity of the heat shock factor HSF-1 programs the insulin-receptor daf-2 in C. elegans

The mechanisms by which maternal stress alters offspring phenotypes remain poorly understood. Here we report that the heat shock transcription factor HSF-1, activated in the C. elegans maternal germline upon stress, epigenetically programs the insulin-like receptor daf-2 by increasing repressive H3K9me2 levels throughout the daf-2 gene. This increase occurs by the recruitment of the C. elegans SETDB1 homolog MET-2 by HSF-1. Increased H3K9me2 levels at daf-2 persist in offspring to downregulate daf-2, activate the C. elegans FOXO ortholog DAF-16 and enhance offspring stress resilience. Thus, HSF-1 activity in the mother promotes the early life programming of the insulin/IGF-1 signaling (IIS) pathway and determines the strategy of stress resilience in progeny.One Sentence SummaryHSF-1 recruits MET-2 to silence daf-2 and mediate early life programming of C. elegans upon stress

Maternal Diet During Pregnancy and COVID-19 Susceptibility of Offspring: The “Thrifty Phenotype Hypothesis” Connection

There is accumulating evidence suggesting that ACE2, the host cell receptor for the spike (S) protein of the SARS-CoV-2, mediates viral entry and infection, is under epigenetic control. Here, we discuss studies suggesting a nutritional strategy for down-regulating ACE2 expression in tissues of offspring through the phenomenon of maternal epigenomic reprogramming mediated by maternal diet. The "thrifty hypothesis" was first proposed by Hales and Barker, which posits that specific genes are programmed based on early-life experience to promote efficient fat deposition and storage in adulthood. Our analysis of the proposed mechanism for "early life programming" in this paper via nutritional modulation of histone acetylation and DNA methylation goes beyond the physiological consequence of boosting the innate cellular resistance to a viral transmission. During the pandemic, where there is still no specific antiviral drug or a widely disseminated vaccine for COVID-19, we hypothesize that an epigenomic nutrition approach may be a practical approach to help mitigate viral transmission offspring.

Primary cilia mediate early life programming of adiposity through lysosomal regulation in the developing mouse hypothalamus

Hypothalamic neurons including proopiomelanocortin (POMC)-producing neurons regulate body weights. The non-motile primary cilium is a critical sensory organelle on the cell surface. An association between ciliary defects and obesity has been suggested, but the underlying mechanisms are not fully understood. Here we show that inhibition of ciliogenesis in POMC-expressing developing hypothalamic neurons, by depleting ciliogenic genes IFT88 and KIF3A, leads to adulthood obesity in mice. In contrast, adult-onset ciliary dysgenesis in POMC neurons causes no significant change in adiposity. In developing POMC neurons, abnormal cilia formation disrupts axonal projections through impaired lysosomal protein degradation. Notably, maternal nutrition and postnatal leptin surge have a profound impact on ciliogenesis in the hypothalamus of neonatal mice; through these effects they critically modulate the organization of hypothalamic feeding circuits. Our findings reveal a mechanism of early life programming of adult adiposity, which is mediated by primary cilia in developing hypothalamic neurons.

The developmental support hypothesis: adaptive plasticity in neural development in response to cues of social support

Across mammals, cues of developmental support, such as touching, licking or attentiveness, stimulate neural development, behavioural exploration and even overall body growth. Why should such fitness-related traits be so sensitive to developmental conditions? Here, we review what we term the ‘developmental support hypothesis’, a potential adaptive explanation of this plasticity. Neural development can be a costly process, in terms of time, energy and exposure. However, environmental variability may sometimes compromise parental care during this costly developmental period. We propose this environmental variation has led to the evolution of adaptive plasticity of neural and behavioural development in response to cues of developmental support, where neural development is stimulated in conditions that support associated costs. When parental care is compromised, offspring grow less and adopt a more resilient and stress-responsive strategy, improving their chances of survival in difficult conditions, similar to existing ideas on the adaptive value of early-life programming of stress. The developmental support hypothesis suggests new research directions, such as testing the adaptive value of reduced neural growth and metabolism in stressful conditions, and expanding the range of potential cues animals may attend to as indicators of developmental support. Considering evolutionary and ecologically appropriate cues of social support also has implications for promoting healthy neural development in humans. This article is part of the theme issue ‘Life history and learning: how childhood, caregiving and old age shape cognition and culture in humans and other animals’.