Environmental Exposures around Conception: Developmental Pathways Leading to Lifetime Disease Risk

Environment around conception can influence the developmental programme with lasting effects on gestational and postnatal phenotype and with consequences for adult health and disease risk. Peri-conception exposure comprises a crucial part of the ‘Developmental Origins of Health and Disease’ (DOHaD) concept. In this review, we consider the effects of maternal undernutrition experienced during the peri-conception period in select human models and in a mouse experimental model of protein restriction. Human datasets indicate that macronutrient deprivation around conception affect the epigenome, with enduring effects on cardiometabolic and neurological health. The mouse model, comprising maternal low protein diet exclusively during the peri-conception period, has revealed a stepwise progression in altered developmental programming following induction through maternal metabolite deficiency. This progression includes differential effects in extra-embryonic and embryonic cell lineages and tissues, leading to maladaptation in the growth trajectory and increased chronic disease comorbidities. The timeline embraces an array of mechanisms across nutrient sensing and signalling, cellular, metabolic, epigenetic and physiological processes with a coordinating role for mTORC1 signalling proposed. Early embryos appear active participants in environmental sensing to optimise the developmental programme for survival but with the trade-off of later disease. Similar adverse health outcomes may derive from other peri-conception environmental experiences, including maternal overnutrition, micronutrient availability, pollutant exposure and assisted reproductive treatments (ART) and support the need for preconception health before pregnancy.

Post-weaning shifts in microbiome composition and metabolism revealed by over 25 000 pig gut metagenome-assembled genomes

Using a previously described metagenomics dataset of 27 billion reads, we reconstructed over 50 000 metagenome-assembled genomes (MAGs) of organisms resident in the porcine gut, 46.5 % of which were classified as >70 % complete with a <10 % contamination rate, and 24.4 % were nearly complete genomes. Here, we describe the generation and analysis of those MAGs using time-series samples. The gut microbial communities of piglets appear to follow a highly structured developmental programme in the weeks following weaning, and this development is robust to treatments including an intramuscular antibiotic treatment and two probiotic treatments. The high resolution we obtained allowed us to identify specific taxonomic ‘signatures’ that characterize the gut microbial development immediately after weaning. Additionally, we characterized the carbohydrate repertoire of the organisms resident in the porcine gut. We tracked the abundance shifts of 294 carbohydrate active enzymes, and identified the species and higher-level taxonomic groups carrying each of these enzymes in their MAGs. This knowledge can contribute to the design of probiotics and prebiotic interventions as a means to modify the piglet gut microbiome.

Blastocyst trophectoderm endocytic activation, a marker of adverse developmental programming

The mouse preimplantation embryo is sensitive to its environment including maternal dietary protein restriction which can alter the developmental programme and affect lifetime health. Previously, we have shown maternal low protein diet (LPD) causes reduction in blastocyst mTORC1 signalling coinciding with reduced availability of branched-chain amino acids (BCAAs) in surrounding uterine fluid. BCAA deficiency leads to increased endocytosis and lysosome biogenesis in blastocyst trophectoderm (TE), a response to promote compensatory histotrophic nutrition. Here, we first investigated the induction mechanism by individual variation in BCAA deficiency in an in vitro quantitative model of TE responsiveness. We found isoleucine (ILE) deficiency as the most effective activator of TE endocytosis and lysosome biogenesis, with less potent roles for other BCAAs and insulin; cell volume was also influential. TE response to low ILE included upregulation of vesicles comprising megalin receptor and cathepsin-B and the response was activated from blastocyst formation. Second, we identified the transcription factor TFEB as mediating the histotrophic response by translocation from cytoplasm to nucleus during ILE deficiency and in response to mTORC1 inhibition. Lastly, we investigated whether a similar mechanism responsive to maternal nutritional status was found in human blastocysts. Blastocysts from women with high body-mass index, but not the method of fertilisation, revealed stimulated lysosome biogenesis and TFEB nuclear migration. We propose TE lysosomal phenotype as an early biomarker of environmental nutrient stress that may associate with long-term health outcome.

ERK1/2 is an ancestral organising signal in spiral cleavage

Embryonic organisers are signalling centres that instruct the establishment of body plans during animal embryogenesis, thus underpinning animal morphological diversity. In spiral cleavage - a stereotypic developmental programme ancestral to 14, nearly half, of the animal phyla (e.g., molluscs, annelids and flatworms), a cell known as the D-quadrant organiser defines cell fates and the body axes. ERK1/2 specifies the embryonic organiser in molluscs, yet how this signalling cascade exerts organising activity and whether this role is conserved in other spiral cleaving groups is unclear. Here, we demonstrate that ERK1/2 promotes the specification and inductive activity of the D-quadrant organiser in Owenia fusiformis, an early-branching annelid exhibiting ancestral developmental traits. In this species, active di-phosphorylated ERK1/2 mediated by FGF receptor activity localises to the 4d micromere, establishing the bilateral symmetry and specifying the hindgut and trunk mesodermal progenitor. Accordingly, impairing FGFR and ERK1/2 activity, as well as cell communication results in embryos developing anteroventrally radialised. Differential transcriptomic profiling shows the ParaHox cdx and the Notch ligand delta as FGFR/ERK1/2 downstream targets in 4d, further revealing that 4d specification instructs the expression of mesodermal and posterodorsal genes in neighbouring cells, putatively via the Notch pathway. The instructing role of ERK1/2 in the D-quadrant organiser is thus shared between O. fusiformis and molluscs, representing an ancestral trait of spiral cleavage. Altogether, our study begins to dissect the gene network promoting axial patterning and posterior growth in spiral cleavage, revealing extensive mechanistic diversification in body plan specification despite overall conservation of cleavage patterns in Spiralia.

The role of arabinogalactan proteins (AGPs) in fruit ripening—a review

Arabinogalactan proteins (AGPs) are proteoglycans challenging researchers for decades. However, despite the extremely interesting polydispersity of their structure and essential application potential, studies of AGPs in fruit are limited, and only a few groups deal with this scientific subject. Here, we summarise the results of pioneering studies on AGPs in fruit tissue with their structure, specific localization pattern, stress factors influencing their presence, and a focus on recent advances. We discuss the properties of AGPs, i.e., binding calcium ions, ability to aggregate, adhesive nature, and crosslinking with other cell wall components that may also be implicated in fruit metabolism. The aim of this review is an attempt to associate well-known features and properties of AGPs with their putative roles in fruit ripening. The putative physiological significance of AGPs might provide additional targets of regulation for fruit developmental programme. A comprehensive understanding of the AGP expression, structure, and untypical features may give new information for agronomic, horticulture, and renewable biomaterial applications.

Developmentally controlled changes during Arabidopsis leaf development indicate causes for loss of stress tolerance with age

Leaf senescence is the final stage of leaf development and is induced by the gradual occurrence of age-related changes (ARCs). The process of leaf senescence has been well described, but the cellular events leading to this process are still poorly understood. By analysis of progressively ageing, but not yet senescing, Arabidopsis thaliana rosette leaves, we aimed to better understand processes occurring prior to the onset of senescence. Using gene expression analysis, we found that as leaves mature, genes responding to oxidative stress and genes involved in stress hormone biosynthesis and signalling were up-regulated. A decrease in primary metabolites that provide protection against oxidative stress was a possible explanation for the increased stress signature. The gene expression and metabolomics changes occurred concomitantly to a decrease in drought, salinity, and dark stress tolerance of individual leaves. Importantly, stress-related genes showed elevated expression in the early ageing mutant old5 and decreased expression in the delayed ageing mutant ore9. We propose that the decreased stress tolerance with age results from the occurrence of senescence-inducing ARCs that is integrated into the leaf developmental programme, and that this ensures a timely and certain death.

Gibberellin-mediated RGA-LIKE1 degradation regulates embryo sac development in Arabidopsis

Ovule development is essential for plant survival, as it allows correct embryo and seed development upon fertilization. The female gametophyte is formed in the central area of the nucellus during ovule development, in a complex developmental programme that involves key regulatory genes and the plant hormones auxins and brassinosteroids. Here we provide novel evidence of the role of gibberellins (GAs) in the control of megagametogenesis and embryo sac development, via the GA-dependent degradation of RGA-LIKE1 (RGL1) in the ovule primordia. YPet-rgl1Δ17 plants, which express a dominant version of RGL1, showed reduced fertility, mainly due to altered embryo sac formation that varied from partial to total ablation. YPet-rgl1Δ17 ovules followed normal development of the megaspore mother cell, meiosis, and formation of the functional megaspore, but YPet-rgl1Δ17 plants had impaired mitotic divisions of the functional megaspore. This phenotype is RGL1-specific, as it is not observed in any other dominant mutants of the DELLA proteins. Expression analysis of YPet-rgl1Δ17 coupled to in situ localization of bioactive GAs in ovule primordia led us to propose a mechanism of GA-mediated RGL1 degradation that allows proper embryo sac development. Taken together, our data unravel a novel specific role of GAs in the control of female gametophyte development.

Housing microbial symbionts: evolutionary origins and diversification of symbiotic organs in animals

In many animal hosts, microbial symbionts are housed within specialized structures known as symbiotic organs, but the evolutionary origins of these structures have rarely been investigated. Here, I adopt an evolutionary developmental (evo-devo) approach, specifically to apply knowledge of the development of symbiotic organs to gain insights into their evolutionary origins and diversification. In particular, host genetic changes associated with evolution of symbiotic organs can be inferred from studies to identify the host genes that orchestrate the development of symbiotic organs, recognizing that microbial products may also play a key role in triggering the developmental programme in some associations. These studies may also reveal whether higher animal taxonomic groups (order, class, phylum, etc.) possess a common genetic regulatory network for symbiosis that is latent in taxa lacking symbiotic organs, and activated at the origination of symbiosis in different host lineages. In this way, apparent instances of convergent evolution of symbiotic organs may be homologous in terms of a common genetic blueprint for symbiosis. Advances in genetic technologies, including reverse genetic tools and genome editing, will facilitate the application of evo-devo approaches to investigate the evolution of symbiotic organs in animals. This article is part of the theme issue ‘The role of the microbiome in host evolution’.

Division of labour among culms in the clonal reed Arundo donax (Poaceae) is underlain by their pre-determined hydraulic structure

Clonal plants present an interesting example of division of labour among their ramets. Here we elaborated on hydraulic structure in respect to the division of labour among ramets in Arundo donax, a perennial clonal reed. Mature clones have three shoot types: (1) large mostly flowering; (2) medium mostly vegetative and (3) small vegetative. The shoots grow from buds initiating in the upper side of underground rhizomes, and the shoot growth is primary with vasculature produced from the procambium. We tested whether the number of vascular strands in a shoot has a fixed developmental programme or follows a flexible developmental pattern, and we found that the number of vascular strands strongly differs between shoot types. Large shoots on average have 560 vascular strands with both the widest vessels and significantly highest hydraulic conductivity. Medium ones and small shoots have 409 and 102 on average, respectively, with narrower vessels and with low conductivity. Thus, the shoot apices have three alternative developmental programmes. Apparently, a clone is built of functionally different modular units that enable Arundo donax to maximize its potential in a heterogeneous environment. Although the smaller culms do not contribute directly to the sexual reproduction of the clone, under stress their safer hydraulic system offers them a better chance of survival.

Comparative characterization of microbiota between the sibling species of tea geometrid moth Ectropis obliqua Prout and E. grisescens Warren

For a wide range of insect species, the microbiota has potential roles in determining host developmental programme, immunity and reproductive biology. The tea geometrid moths Ectropis obliqua and E. grisescens are two closely related species that mainly feed on tea leaves. Although they can mate, infertile hybrids are produced. Therefore, these species provide a pair of model species for studying the molecular mechanisms of microbiotal involvement in host reproductive biology. In this study, we first identified and compared the compositions of microbiota between these sibling species, revealing higher microbiotal diversity for E. grisescens. The microbiota of E. obliqua mainly comprised the phyla Firmicutes, Proteobacteria and Cyanobacteria, whereas that of E. grisescens was dominated by Proteobacteria, Actinobacteria and Firmicutes. At the genus level, the dominant microbiota of E. grisescens included Wolbachia, Enterobacter and Pseudomonas and that of E. obliqua included Melissococcus, Staphylococcus and Enterobacter. Furthermore, we verified the rate of Wolbachia to infect 80 samples from eight different geographical populations, and the results supported that only E. grisescens harboured Wolbachia. Taken together, our findings indicate significantly different microbiotal compositions for E. obliqua and E. grisescens, with Wolbachia possibly being a curial factor influencing the reproductive isolation of these species. This study provides new insight into the mechanisms by which endosymbiotic bacteria, particularly Wolbachia, interact with sibling species.