Developmental phenotypic plasticity: where internal programming meets the external environment

Developmental plasticity has long been the focus of research in both evolutionary ecology and molecular genetics. Recently, the concept of ontogenetic contingency has been proposed to indicate the dependence of plastic responses on the timing and sequence of developmental events. Also, the idea of the developmental reaction norm has been put forward to indicate the complex interactions among development, phenotypic plasticity, and allometry of different structures. Finally, for the first time, studies ranging from the ecological to the molecular aspects of the same plastic response are available on insect and flowering plant model systems.     

Developmental changes in the content of oestrogen receptors in the hypothalamus of the female rat.

Hypothalamic cytosol and nuclear oestrogen receptors are present at birth. A 2-fold increase in cytoplasmic receptor content occurs by the second week, whereas the first significant and equivalent increase in nuclear receptor occurs in the fourth week. The latter reflects reported increases in oestradiol availability thought to lead to complete feminine sexual differentiation. The presence of nuclear receptors in the newborn suggests a requirement for oestrogenic stimulation in early development.     

Developmental programming by maternal obesity in 2015: Outcomes,mechanisms, and potential interventions

This article is part of a Special Issue “SBN 2014”.Obesity in women of child-bearing age is a growing problem in developed and developing countries. Evidence from human studies indicates that maternal BMI correlates with offspring adiposity from an early age and predisposes to metabolic disease in later life. Thus the early life environment is an attractive target for intervention to improve public health. Animal models have been used to investigate the specific physiological outcomes and mechanisms of developmental programming that result from exposure to maternal obesity in utero. From this research, targeted intervention strategies can be designed. In this review we summarise recent progress in this field, with a focus on cardiometabolic disease and central control of appetite and behaviour. We highlight key factors that may mediate programming by maternal obesity, including leptin, insulin, and ghrelin. Finally, we explore potential lifestyle and pharmacological interventions in humans and the current state of evidence from animal models.     

Developmental programming of skeletal muscle phenotype/metabolism

Skeletal muscle is a highly dynamic and malleable tissue that is able to adapt to different stimuli placed upon it, both during gestation and after birth, ultimately resulting in anatomical changes to muscle fibre composition. Variation in nutrient supply throughout gestation is common, whether in livestock or in the human. The specific effects of maternal nutrition on foetal development are at the forefront of scientific research. However, results describing how different maternal feeding strategies affect skeletal muscle fibre development in the offspring are not fully consistent, even where the same time windows during gestation have been examined. The aim of this study is to determine the effects of increased maternal nutrition (above the recommended levels) on the Musculus semitendinosus phenotype of progeny. In all, 24 pregnant sows were assigned to one of four feeding regimes during gestation; T1 (control group): 30 MJ digestible energy per day (MJ DE/day) throughout gestation, T2: same as that for T1 but increased to 60 MJ DE/day from 25 to 50 days of gestation (dg), T3: same as that for T1 but increased to 60 MJ DE/day from 50 to 80 dg, T4: same as that for T1 but increased nutrition to 60 MJ DE/day from 25 to 80 dg. Light- and heavy-weight littermate pairs of the same sex were selected at birth and individually fed to slaughter (c. 158 days). Histochemical and immunohistochemical staining were used to identify the predominantly oxidative (deep) and less oxidative (superficial) regions of the M. semitendinosus, and to determine total fibre number and proportions of fibre types. The results demonstrate that increased maternal nutrition alters skeletal muscle phenotype in the offspring by changing fibre-type proportions, leading to an increased oxidative capacity due to an increase in Type IIA fibres. No change in total muscle area, total muscle fibre number, or fibre cross-sectional area is observed. The precise molecular mechanism(s) by which these findings occur is being investigated.     

Developmental programming: deficits in reproductive hormone dynamics and ovulatory outcomes in prenatal, testosterone-treated sheep

Prenatal testosterone excess leads to neuroendocrine, ovarian, and metabolic disruptions, culminating in reproductive phenotypes mimicking that of women with polycystic ovary syndrome (PCOS). The objective of this study was to determine the consequences of prenatal testosterone treatment on periovulatory hormonal dynamics and ovulatory outcomes. To generate prenatal testosterone-treated females, pregnant sheep were injected intramuscularly (days 30-90 of gestation, term=147 days) with 100 mg of testosterone-propionate in cottonseed oil semi-weekly. Female offspring born to untreated control females and prenatal testosterone-treated females were then studied during their first two breeding seasons. Sheep were given two injections of prostaglandin F2alpha 11 days apart, and blood samples were collected at 2-h intervals for 120 h, 10-min intervals for 8 h during the luteal phase (first breeding season only), and daily for an additional 15 days to characterize changes in reproductive hormonal dynamics. During the first breeding season, prenatal testosterone-treated females manifested disruptions in the timing and magnitude of primary gonadotropin surges, luteal defects, and reduced responsiveness to progesterone negative feedback. Disruptions in the periovulatory sequence of events during the second breeding season included: 1) delayed but increased preovulatory estradiol rise, 2) delayed and severely reduced primary gonadotropin surge in prenatal testosterone-treated females having an LH surge, 3) tendency for an amplified secondary FSH surge and a shift in the relative balance of FSH regulatory proteins, and 4) luteal responses that ranged from normal to anovulatory. These outcomes are likely to be of relevance to developmental origin of infertility disorders and suggest that differences in fetal exposure or fetal susceptibility to testosterone may account for the variability in reproductive phenotypes.     

In vitro receptor autoradiography: a map for exploring the hypothalamus.

In rabbits and guinea pigs, hypothalamic sites for prostaglandin E2 (PGE2) action were studied by means of in vitro receptor autoradiography. The density of PGE2 binding sites (probably PGE2 receptors) was the highest in the anterior wall of the third ventricle (A3V). This result is consistent in all mammalian species ever studied, suggesting a fundamental role of the A3V in the hypothalamic action of PGE2, such as fever.     

Blood supply of the rat hypothalamus. V. The medial hypothalamus (nucleus ventromedialis, nucleus dorsomedialis, nucleus perifornicalis)

Using the India ink double-perfusion technique, the blood vessels of the rat's medial hypothalamus were reconstructed from serial sections. The area studied comprised the ventromedial, dorsomedial and perifornical nuclei. The arterial supply of this territory comes from the middle hypothalamic and the anterior, middle and posterior tuberal arteries. The drainage is strictly undirectional: ventralward by the anterior, middle and posterior ventromedial, the posteromedial and posterolateral hypothalamic veins, all ending in the basal vein. The arteries of the ventromedial and dorsomedial nuclei are distinct from those of the arcuate nucleus and median eminence, and their drainage is not connected with the portal vessels. The nuclei studied, even at the levels of their subdivisions, possess own arteries whose territories of supply can well be distinguished with a minimum of overlap. The topography of these arteries is described in detail. The medial hypothalamus has no vascular connections with other regions of the diencephalon including the thalamus.     

Developmental switch in neuropeptide Y and melanocortin effects in the paraventricular nucleus of the hypothalamus

Homeostatic regulation of energy balance in rodents changes dramatically during the first 3 postnatal weeks. Neuropeptide Y (NPY) and melanocortin neurons in the arcuate nucleus, a primary energy homeostatic center in adults, do not fully innervate the paraventricular nucleus (PVN) until the third postnatal week. We have identified two classes of PVN neurons responsive to these neuropeptides, tonically firing neurosecretory (NS) and burst-firing preautonomic (PA) cells. In neonates, NPY could inhibit GABAergic inputs to nearly all NS and PA neurons, while melanocortin regulation was minimal. However, there was a dramatic, age-dependent decrease in NPY responses specifically in the PA neurons, and a 3-fold increase in melanocortin responses in NS cells. These age-dependent changes were accompanied by changes in spontaneous GABAergic currents onto these neurons. This primarily NPYergic regulation in the neonates likely promotes the positive energy balance necessary for growth, while the developmental switch correlates with maturation of homeostatic regulation of energy balance.