Ontogeny Of Development Research Articles

Application of the heterochrony framework to the study of behavior and cognition

Heterochrony, or the evolution of ontogeny, has been well studied in embryology and skeletal development, providing insight into morphological and genetic mechanisms of evolution.1-5 However, heterochronic studies of behavior and cognition lag behind in comparison. In a recent study we investigated the ontogeny of social behavior and cognition in humans’ closest living relatives, chimpanzees (Pan troglodytes) and bonobos (Pan paniscus). These two species are estimated to have had a chimpanzee-like common ancestor between 0.86 and 1.8 mya.6,7 Bonobos have been argued to exhibit morphological indications of paedomorphism relative to chimpanzees, especially in the cranium, and to exhibit paedomorphic behavior as adults.6-11 We found that bonobos exhibit developmental delays relative to chimpanzees in several aspects of their social behavior and cognition. Here, we describe how placing these results in the framework of heterochrony contributes to understanding behavioral and cognitive differences between adults of these two species and to our knowledge of hominid evolution in general.

Developmental ontogeny of autoantigens associated with localized autoimmunity in murine testis and epididymis

Experimental autoimmune orchitis (EAO) with experimental autoimmune epididymitis (EAE) can be induced in mice by immunization with testicular antigens emulsified in adjuvants. On immunization with syngeneic testicular germ cells (TGC) alone, EAO with no EAE is induced in mice. Recently, we found that EAE with no EAO can be induced in vasectomized mice by immunization with TGC. In the present study, we investigated the appearance of autoantigens relevant to EAO and EAE by reacting each immune serum sample with testes and epididymides extracts from normal mice of various ages by immunoblotting. The results showed that the antisera obtained from mice with EAO lesions specifically defined testicular antigens with molecular weights of 15 kDa, 40 kDa, 75 kDa and >200 kDa from 4 weeks of age, but the antisera obtained from mice with EAE strongly defined both testicular and epididymal antigens of 25 kDa from 5 and 8 weeks of ages, respectively. These results suggest that vasectomy changes the target autoantigens in TGC-induced autoimmunity.

A rich TILLING resource for studying gene function in Brassica rapa.

BackgroundThe Brassicaceae family includes the model plant Arabidopsis thaliana as well as a number of agronomically important species such as oilseed crops (in particular Brassica napus, B. juncea and B. rapa) and vegetables (eg. B. rapa and B. oleracea).Separated by only 10-20 million years, Brassica species and Arabidopsis thaliana are closely related, and it is expected that knowledge obtained relating to Arabidopsis growth and development can be translated into Brassicas for crop improvement. Moreover, certain aspects of plant development are sufficiently different between Brassica and Arabidopsis to warrant studies to be carried out directly in the crop species. However, mutating individual genes in the amphidiploid Brassicas such as B. napus and B. juncea may, on the other hand, not give rise to expected phenotypes as the genomes of these species can contain up to six orthologues per single-copy Arabidopsis gene. In order to elucidate and possibly exploit the function of redundant genes for oilseed rape crop improvement, it may therefore be more efficient to study the effects in one of the diploid Brassica species such as B. rapa. Moreover, the ongoing sequencing of the B. rapa genome makes this species a highly attractive model for Brassica research and genetic resource development.ResultsSeeds from the diploid Brassica A genome species, B. rapa were treated with ethyl methane sulfonate (EMS) to produce a TILLING (Targeting Induced Local Lesions In Genomes) population for reverse genetics studies. We used the B. rapa genotype, R-o-18, which has a similar developmental ontogeny to an oilseed rape crop. Hence this resource is expected to be well suited for studying traits with relevance to yield and quality of oilseed rape. DNA was isolated from a total of 9,216 M2 plants and pooled to form the basis of the TILLING platform. Analysis of six genes revealed a high level of mutations with a density of about one per 60 kb. This analysis also demonstrated that screening a 1 kb amplicon in just one third of the population (3072 M2 plants) will provide an average of 68 mutations and a 97% probability of obtaining a stop-codon mutation resulting in a truncated protein. We furthermore calculated that each plant contains on average ~10,000 mutations and due to the large number of plants, it is predicted that mutations in approximately half of the GC base pairs in the genome exist within this population.ConclusionsWe have developed the first EMS TILLING resource in the diploid Brassica species, B. rapa. The mutation density in this population is ~1 per 60 kb, which makes it the most densely mutated diploid organism for which a TILLING population has been published. This resource is publicly available through the RevGenUK reverse genetics platform http://revgenuk.jic.ac.uk.

Evo-devo and the I.I. Schmalhausen concept of the evolution of ontogeny

Evo-devo is considered a special field of knowledge emphasizing the role of developmental processes and mechanisms in evolution and integrating the data of many disciplines studying various structural levels of biosphere organization. A mechanical approach to estimation of events is regarded as a specific feature of the evo-devo concept. In our opinion, the I.I. Schmalhausen concept of the evolution of ontogeny, opposing the reductionist approach of many contemporary evo-devo adherents, can be regarded as the fundamental basis of evo-devo.

There's something afoot in the evolution of ontogenies

Allometry, the association between size and shape, has long been considered an evolutionary constraint because of its ability to channel variation in particular directions in response to evolution of size. Several recent studies, however, have demonstrated that allometries themselves can evolve. Therefore, constraints based on these allometries are not constant over long evolutionary time scales. The changes in ontogeny appear to have a clear adaptive basis, which establishes a feedback loop from adaptive change of ontogeny through the altered developmental constraints to the potential for further evolutionary change. Altogether, therefore, this new evidence underscores the tight interactions between developmental and ecological factors in the evolution of morphological traits.

Adipose Tissue Inflammation: Developmental Ontogeny and Consequences of Gestational Nutrient Restriction in Offspring

Increasing adiposity predisposes to the development of the metabolic syndrome, in part, through adipose tissue dysregulation and inflammation. In addition, offspring nutrient restricted (NR) in utero can exhibit an increased risk of early-onset insulin resistance and obesity, although the mechanisms remain unclear. We aimed to: 1) define adipose tissue ontogeny of key proinflammatory and endoplasmic reticulum stress gene expression from late fetal to early adult life and 2) examine the impact on these genes in gestational nutrient restriction. Pregnant sheep were fed 100% (control) or 50% (NR) of their nutritional requirements between early to mid (28–80 d, term ∼147 d) or late (110–147 d) gestation. In control offspring, toll-like receptor 4 (TLR4), and the macrophage marker CD68, peaked at 30 d of life before declining. IL-18 peaked at 6 months of age, whereas the endoplasmic reticulum chaperone glucose-regulated protein 78 peaked at birth and subsequently declined through postnatal life. TLR4 and CD68 positively correlated with relative adipose tissue mass and with each other. Early to midgestational NR offspring had decreased abundance of IL-18 at 6 months of age. In late gestational NR offspring, CD68 was significantly lower at birth, a pattern that reversed in juvenile offspring, coupled with increased TLR4 abundance. In conclusion, the in utero nutritional environment can alter the adipose tissue inflammatory profile in offspring. This may contribute to the increased risk of insulin resistance or obesity, dependent on the timing of nutrient restriction. Establishing the optimal maternal diet during pregnancy could reduce the burden of later adult disease in the offspring.

Adipose Tissue Inflammation: Developmental Ontogeny and Consequences of Gestational Nutrient Restriction in Offspring

Increasing adiposity predisposes to the development of the metabolic syndrome, in part, through adipose tissue dysregulation and inflammation. In addition, offspring nutrient-restricted (NR) in utero can exhibit an increased risk of early-onset insulin resistance and obesity, although the mechanisms remain unclear. We aimed to: 1) define adipose tissue ontogeny of key proinflammatory and endoplasmic reticulum stress gene expression from late fetal to early adult life and 2) examine the impact on these genes in gestational nutrient restriction. Pregnant sheep were fed 100% (control) or 50% (NR) of their nutritional requirements between early to mid (28-80 d, term approximately 147 d) or late (110-147 d) gestation. In control offspring, toll-like receptor 4 (TLR4), and the macrophage marker CD68, peaked at 30 d of life before declining. IL-18 peaked at 6 months of age, whereas the endoplasmic reticulum chaperone glucose-regulated protein 78 peaked at birth and subsequently declined through postnatal life. TLR4 and CD68 positively correlated with relative adipose tissue mass and with each other. Early to midgestational NR offspring had decreased abundance of IL-18 at 6 months of age. In late gestational NR offspring, CD68 was significantly lower at birth, a pattern that reversed in juvenile offspring, coupled with increased TLR4 abundance. In conclusion, the in utero nutritional environment can alter the adipose tissue inflammatory profile in offspring. This may contribute to the increased risk of insulin resistance or obesity, dependent on the timing of nutrient restriction. Establishing the optimal maternal diet during pregnancy could reduce the burden of later adult disease in the offspring.

Developmental programming: prenatal androgen excess disrupts ovarian steroid receptor balance

Steroid hormones play an important role in reproduction and the receptors through which they signal change in a developmental time, follicle stage, and cell-specific manner. Disruption in steroid receptor expression affects follicle formation and differentiation. In this study, using prenatal testosterone (T) and dihydrotestosterone (DHT)-treated female sheep as model systems, we tested the hypothesis that prenatal androgen excess disrupts the developmental ontogeny of ovarian steroid receptor protein expression. Pregnant Suffolk ewes were injected twice weekly with T propionate or DHT propionate (a non-aromatizable androgen) in cottonseed oil from days 30 to 90 of gestation. Changes in ovarian estrogen receptors (ER; ESR1, ESR2), androgen receptor (AR) and progesterone receptor (PGR) proteins were determined at fetal (days 90 and 140), postpubertal (10 months), and adult (21 months; only prenatal T-treated sheep studied) ages by immunohistochemistry. Prenatal T and DHT treatment induced selective increase in AR but not ER or PGR expression in the stroma and granulosa cells of fetal days 90 and 140 ovaries. An increase in ESR1 and decrease in ESR2 immunostaining coupled with increased AR expression were evident in granulosa cells of antral follicles of 10- and 21-month-old prenatal T but not DHT-treated females (analyzed only at 10 months). These findings provide evidence that an early increase in ovarian AR is the first step in the altered ovarian developmental trajectory of prenatal T-treated females, and manifestations of postnatal ovarian dysfunction are likely facilitated via altered equilibrium of antral follicular granulosa cell ER/AR protein expression.

RNA regulation of epigenetic processes

There is increasing evidence that dynamic changes to chromatin, chromosomes and nuclear architecture are regulated by RNA signalling. Although the precise molecular mechanisms are not well understood, they appear to involve the differential recruitment of a hierarchy of generic chromatin modifying complexes and DNA methyltransferases to specific loci by RNAs during differentiation and development. A significant fraction of the genome-wide transcription of non-protein coding RNAs may be involved in this process, comprising a previously hidden layer of intermediary genetic information that underpins developmental ontogeny and the differences between species, ecotypes and individuals. It is also evident that RNA editing is a primary means by which hardwired genetic information in animals can be altered by environmental signals, especially in the brain, indicating a dynamic RNA-mediated interplay between the transcriptome, the environment and the epigenome. Moreover, RNA-directed regulatory processes may also transfer epigenetic information not only within cells but also between cells and organ systems, as well as across generations.

Ontogeny of adipokine expression in neonatal pig adipose tissue

This study examined ontogeny of development for a range of adipokines in neonatal adipose tissue. Pigs (Sus scrofa) were selected across six litters for sampling subcutaneous (SQ) and perirenal (PR) adipose tissues at d1, d4, d7 or d21 of age and total RNA extraction. Reverse transcription and real-time PCR were used to quantify mRNA abundance for: leptin, adiponectin, interleukin 1beta (IL-1beta), IL-6, IL-8, IL-10, IL-15, tumor necrosis factor alpha (TNFalpha), haptoglobin, vascular endothelial growth factor (VEGF), macrophage migration inhibitory factor (MIF), monocyte chemoattractant protein 1 (MCP1) and cyclophilin. Leptin, adiponectin and IL-15 expression increased from d1 to d 21 of age in both SQ and PR. Haptoglobin, VEGF, MIF and IL-8 expression decreased between d1 and d4 of age in SQ. TNFalpha expression was unchanged from d1-7 and then increased at d21. IL-1beta, IL-6 and IL-10 expression were unchanged with age in SQ; whereas IL-1beta and IL-6 mRNA abundance in the PR increased with age. Analysis of the mRNA abundance for these adipokines within adipose tissue from d1 to d21 of age demonstrated that neonatal development of adipokine expression varies among the different adipokines and the internal and external sites of adipose tissue deposition (PR versus SQ).

On the problem of ecological evolution in Volvox

A concept of evolution of ontogeny based on the original data on the comparative biology of volvox development and published paleoclimatic data is presented. Previously, we have demonstrated that evolutionary reorganizations of asexual development in Volvox are related to the changes in the rate, diel rhythms, and light/dark control of cell divisions. Here, we propose that such rearrangements could take place during much of Cenozoic time (e.g., in Eocene and Miocene) as adaptations to short and warm winter day in high latitudes. This proposal is confirmed by experimental data on culturing volvox species with different types of development under short photoperiod.

Developmental Ontogeny of Adipose Cellularity and Gene Expression in the Neonatal Piglet

Childhood obesity has reached epidemic proportions and its prevention is a public health priority. Postnatal weight gain may be a determinant for the development of obesity. The piglet is a common preclinical model for the human infant; however, little is known about adipocyte development and lipogenic gene expression in neonatal piglets. Subcutaneous and renal adipose tissue were obtained from sow‐reared piglets (n = 12 female; n = 12 male) at d2, 7, 14 and 21 postpartum. No effect of gender was found, so data were pooled by day. Adipocyte number and size were determined using a Coulter counter and gene expression measured by real‐time PCR. Subcutaneous adipocyte cell number/mg tissue was greater (p<0.05) at d2 than d7, 14 or 21 due to an increase in cell size with age. The smallest sized cells (20–30 μm) represented 72% of adipocytes on d2, but only 21% by d21. Cells sized 50–70 μm increased (p<0.05) from 4% to 32% between d2 and d21. The greatest changes occurred between d2 and d7 postpartum. The mRNA expression of CEBP‐α, C/EBP‐β and LPL in renal adipose tissue increased over time. GLUT‐4 and PPAR‐γ mRNA expression were greater at d21 than d7 and d14. In summary, piglets displayed rapid changes in adipocyte cell size, which was reflected in the pattern of adipogenic and lipogenic gene expression. These findings are similar to the human and emphasizes the utility of the porcine model. Funded by the Illinois Soybean Association.

Recruitment of Rad50 and MCM Complexes on the Human Beta Globin Locus Control Region (LCR): A Novel Role for LCR Hypersensitive Site 4 (HS4).

The human beta globin locus control region (LCR) aids in the establishment of an open chromatin configuration thereby facilitating the expression of linked downstream globin genes in a temporal and spatial manner along the developmental ontogeny. The LCR also functions as a classical enhancer of the beta like globin genes. The four DNAase-I hypersensitive regions (HS 1–4) on the LCR are believed to act as nucleation centers for the assembly of multi-protein transcriptional complexes that interact with the distant gene promoters. Present work is focused on characterizing the protein complex assemblies on the HS4 region and delineating their function in the context of goblin gene regulation. Our finding shows an assembly of a 2–5 MDa complex on the HS4 locus that is both erythroid restricted and sequence specific. Electrophoretic mobility shift assays (EMSA) were performed using K562 and HeLa nuclear extracts and ∼35mer double stranded oligonucleotides with 7 bp overlaps tiling the entire core HS4 sequence. We detected prominent K562 specific bands formed with an AT rich 39 bp HS4 sequence. Sequence specificity of DNA-protein complex formation on this AT rich sequence was determined by competitive EMSA assays. Gel supershift assays with a wide range of antibodies and subsequent partial purification of this multiprotein complex followed by the LC-MS/MS analysis reveal the presence of a mini chromosome maintenance (MCM) complex that is associated with the DNA replication, DNA repair associated Rad50-Mre-11-NBS-1 complex, histone acetyl transferase p300 and DNA binding transcription factors ILF2 (NF45) and ILF3 (NF90). The association of these proteins was determined by co-immunoprecipitation experiments. Chromatin immunoprecipitation (ChIP) experiments demonstrate the in vivo recruitment of these proteins on the HS4 region of the LCR. We are currently working on further characterization and functional studies of this complex and its significance on the role of the LCR in DNA replication and repair.

Evolution of ontogeny: linking epigenetic remodeling and genetic adaptation in skeletal structures

Evolutionary diversifications are commonly attributed to the continued modifications of a conserved genetic toolkit of developmental pathways, such that complexity and convergence in organismal forms are assumed to be due to similarity in genetic mechanisms or environmental conditions. This approach, however, confounds the causes of organismal development with the causes of organismal differences and, as such, has only limited utility for addressing the cause of evolutionary change. Molecular mechanisms that are closely involved in both developmental response to environmental signals and major evolutionary innovations and diversifications are uniquely suited to bridge this gap by connecting explicitly the causes of within-generation variation with the causes of divergence of taxa. Developmental pathways of bone formation and a common role for bone morphogenetic proteins (BMPs) in both epigenetic bone remodeling and the evolution of major adaptive diversifications provide such opportunity. We show that variation in timing of ossification can result in similar phenotypic patterns through epigenetically induced changes in gene expression and propose that both genetic accommodation of environmentally induced developmental pathways and flexibility in development across environments evolve through heterochronic shifts in bone maturation relative to exposure to unpredictable environments. We suggest that such heterochronic shifts in ossification can not only buffer development under fluctuating environments while maintaining epigenetic sensitivity critical for normal skeletal formation, but also enable epigenetically induced gene expression to generate specialized morphological adaptations. We review studies of environmental sensitivity of BMP pathways and their regulation of formation, remodeling, and repair of cartilage and bone to examine the hypothesis that BMP-mediated skeletal adaptations are facilitated by evolved reactivity of BMPs to external signals. Surprisingly, no empirical study to date has identified the molecular mechanism behind developmental plasticity in skeletal traits. We outline a conceptual framework for future studies that focus on mediation of phenotypic plasticity in skeletal development by the patterns of BMP expression.

Differences in resprouting ability are not related to seed size or seedling growth in four riparian woody species

Summary Resprouting is a key plant attribute facilitating persistence in disturbance‐prone environments. Resprouting ability in seedlings may depend on both developmental ontogeny and seed size. However, the relationships between these factors are not well explored, especially for woody species with comparatively small seeds and epigeal germination. We investigated resprouting capacity in seedlings from four subtropical, riparian, Myrtaceous tree species, Melaleuca leucadendra, Asteromyrtus symphyocarpa, Eucalyptus camaldulensis var. obtusa and Tristaniopsis laurina, displaying these characteristics. We recorded resprouting in response to simulated disturbance as a function of seed mass and developmental age (5–150 days post‐emergence) and examined the acquisition of resprouting ability in relation to growth and biomass allocation patterns. Patterns of resprouting were distinct among species, but the acquisition of resprouting ability was not determined by seed mass. The ‘small’ seeded M. leucadendra and the ‘intermediate’ seeded E. camaldulensis showed unexpectedly high shoot resprouting vigour from cotyledon stage (70% resprouting at 5 days post‐emergence), as well as greatest ongoing allocation to root mass and lateral root development. In contrast, in A. symphyocarpa (another species with ‘intermediate’ seed mass) and T. laurina (a ‘large’ seeded species) resprouting rates during early development were much lower (< 10%), although there was a trend towards increasing resprouting ability with age in A. symphyocarpa (> 150 days). Resprouting capacity was also independent of seedling size and relative growth rate. Our results indicate that the size‐dependency of resprouting capacity varies considerably among these species. This suggests physiological and morphological species traits other than those directly related to reserve size or relative growth rate may convey survivorship in river environments. Our findings show that resprouting capacity was not related to seed size and seedling growth patterns in these four species. This is different to evidence from comparative studies undertaken in fire‐prone and other temperate environments. A broader survey of seedling resprouting ability including more species is required to determine the generality of our findings in riparian species.

Localization and developmental ontogeny of the pro-apoptotic Bnip3 mRNA in the postnatal rat cortex and hippocampus

Naturally occurring cell death occurs during the first two postnatal weeks in the rat cortex and hippocampus. During this process, apoptosis is initiated by activating or altering expression of pro-apoptotic members of the Bcl-2 family. Bnip3 is a pro-apoptotic member of the Bcl-2 family that induces cell death by opening the mitochondrial permeability transition pore. To date, Bnip3 expression in the central nervous system has only been examined during hypoxia-mediated apoptosis in the adult rat brain. In this study, we investigated the localization and ontogeny of Bnip3 mRNA expression in the postnatal male and female rat brain. Bnip3 mRNA was localized by in situ hybridization in the neonatal cortex, hippocampus, habenula and thalamus. Using quantitative real-time RT-PCR, Bnip3 mRNA levels were found to be greatest at postnatal day 6.5 in the female anterior and posterior cingulate cortices and hippocampus. Bnip3 mRNA expression also increased in the male anterior cingulate cortex at postnatal day 6.5. However, a developmental change in Bnip3 levels did not occur in the male posterior cingulate cortex and hippocampus. In the anterior cingulate cortex on postnatal day 6.0 and adulthood, female rats had significantly greater levels of Bnip3 mRNA compared to that of males. Altering levels of testosterone in the neonatal rat did not alter the sex differences in Bnip3 mRNA levels. The transient increase in Bnip3 mRNA expression correlates with naturally occurring cell death in the neonatal rat cortex and hippocampus. Thus, Bnip3 may be a mediator of developmental apoptosis in the postnatal rat brain.

The taurine transporter: mechanisms of regulation

Taurine transport undergoes an adaptive response to changes in taurine availability. Unlike most amino acids, taurine is not metabolized or incorporated into protein but remains free in the intracellular water. Most amino acids are reabsorbed at rates of 98-99%, but reabsorption of taurine may range from 40% to 99.5%. Factors that influence taurine accumulation include ionic environment, electrochemical charge, and post-translational and transcriptional factors. Among these are protein kinase C (PKC) activation and transactivation or repression by proto-oncogenes such as WT1, c-Jun, c-Myb and p53. Renal adaptive regulation of the taurine transporter (TauT) was studied in vivo and in vitro. Site-directed mutagenesis and the oocyte expression system were used to study post-translational regulation of the TauT by PKC. Reporter genes and Northern and Western blots were used to study transcriptional regulation of the taurine transporter gene (TauT). We demonstrated that (i) the body pool of taurine is controlled through renal adaptive regulation of TauT in response to taurine availability; (ii) ionic environment, electrochemical charge, pH, and developmental ontogeny influence renal taurine accumulation; (iii) the fourth segment of TauT is involved in the gating of taurine across the cell membrane, which is controlled by PKC phosphorylation of serine 322 at the post-translational level; (iv) expression of TauT is repressed by the p53 tumour suppressor gene and is transactivated by proto-oncogenes such as WT1, c-Jun, and c-Myb; and (v) over-expression of TauT protects renal cells from cisplatin-induced nephrotoxicity.

Comparative postnatal ontogeny of the skull in the australidelphian metatherian Dasyurus albopunctatus (Marsupialia: Dasyuromorpha: Dasyuridae)

We describe the cranial ontogeny of an australidelphian marsupial, Dasyurus albopunctatus, using a combination of qualitative and quantitative approaches. We examined in detail qualitative morphological changes of just-weaned individuals as compared to old adults; specifically, changes in 31 morphological structures (e.g., processes, foramina) and 38 changes in cranial joints. We also interpreted growth-invariant structures in terms of their functional relevance. We performed a multivariate allometry analysis based on 14 cranial measurements taken from 31 specimens encompassing the entire postweaning period. Three variables (height of occipital plate, breadth of braincase, and height of mandible) showed the same allometric trends in D. albopunctatus and the three marsupial species studied previously in the same framework (Didelphis albiventris, Lutreolina crassicaudata, and Dromiciops gliroides). In addition, D. albopunctatus shared allometric trends in two variables (length of the upper postcanine row and length of the orbit) with the microbiotheriid D. gliroides. Most of the growth trends observed are interpreted as linked to the predominantly carnivorous dietary habit of adult D. albopunctatus. Because dasyuromorphians are most likely basal to the major Australasian radiation of marsupials, knowledge of ontogenetic changes in D. albopunctatus may shed light on the evolution of ontogeny in the highly diverse Australasian marsupial fauna.

Ontogeny and nutritional programming of adiposity in sheep: potential role of glucocorticoid action and uncoupling protein-2

Increased glucocorticoid action and adipose tissue inflammation contribute to excess adiposity. These adaptations may be enhanced in offspring exposed to nutrient restriction (NR) in utero, thereby increasing their susceptibility to later obesity. We therefore determined the developmental ontogeny of glucocorticoid receptor (GR), 11beta-hydroxysteroid dehydrogenase (11betaHSD) types 1 and 2, and uncoupling protein (UCP)-2 mRNA in perirenal adipose tissue between late gestation and 6 mo after birth in the sheep, as well as the effect of maternal NR targeted between early to mid (28-80 days, term approximately 147 days)- or late (110-147 days) gestation. GR and 11betaHSD1 mRNA increased with fat mass and were all maximal within the 6-mo observation period. 11betaHSD2 mRNA abundance demonstrated a converse decline, whereas UCP2 peaked at 30 days. GR and 11betaHSD1 mRNA abundance were strongly correlated with total and relative perirenal adipose tissue weight, and UCP2 was strongly correlated with GR and 11betaHSD1 mRNA. Early- to midgestational NR increased GR, 11betaHSD1, and UCP2 mRNA, but decreased 11betaHSD2 mRNA abundance, an adaptation reversed with late-gestational NR. We conclude that the continual rise in glucocorticoid action and fat mass after birth may underlie the development of later obesity. The magnitude of this adaptation is partly dependent on maternal food intake through pregnancy.

Ontogeny and nutritional programming of uncoupling protein‐2 and glucocorticoid receptor mRNA in the ovine lung

This study investigated the developmental and nutritional programming of uncoupling protein-2 (UCP2), glucocorticoid receptor (GR) and 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) mRNA in the sheep lung from the time of uterine attachment to 6 months of age. The effect of maternal nutrient restriction on lung development was determined in early to mid gestation (i.e. 28-80 days gestation, period of maximal placental growth, and embryonic and pseudoglandular stages of fetal lung development) and late gestation (i.e. 110-147 days gestation, period of maximal fetal growth, and canalicular and saccular stages of fetal lung development). Fetal lungs were sampled at 80 and 140 days (term approximately 148 days) gestation, and sheep lungs at 1, 7, 30 days and 6 months. GR and 11betaHSD1 mRNA were maximal at 140 days gestation, whereas UCP2 mRNA peaked at 1 day of age and then declined with postnatal age. Maternal nutrient restriction in both early-to-mid and late gestation had no effect on lung weight, but increased UCP2, GR and 11betaHSD1 mRNA abundance at every sampling age. These findings suggest that the developmental ontogeny of UCP2 mRNA in the ovine lung is under local glucocorticoid hormone action and that maternal nutrient restriction has long-term consequences for UCP2 and GR mRNA abundance in the lung irrespective of its timing.