Maternal Corticosterone Research Articles

Perinatal high fat diet alters glucocorticoid signaling and anxiety behavior in adulthood

Maternal obesity carries significant health risks for offspring that manifest later in life, including metabolic syndrome, cardiovascular disease and affective disorders. Programming of the hypothalamic–pituitary–adrenal (HPA) axis during development mediates both metabolic homeostasis and the response to psychosocial stress in offspring. A diet high in fat alters maternal systemic corticosterone levels, but effects in offspring on limbic brain areas regulating the HPA axis and anxiety behavior are poorly understood. In addition to their role in the response to psychosocial stress, corticosteroid receptors form part of the glucocorticoid signaling pathway comprising downstream inflammatory processes. Increased systemic inflammation is a hallmark of high-fat diet exposure, though altered expression of these genes in limbic brain areas has not been examined. We studied the influence of high-fat diet exposure during pre-weaning development in rats on gene expression in the amygdala and hippocampus by quantitative real-time polymerase chain reaction (PCR), anxiety behavior in the Open field, elevated plus maze and light–dark transition tasks, and corticosterone levels in response to stress by radioimmunoassay. As adults, offspring exposed to perinatal high-fat diet show increased expression of corticosterone receptors in the amygdala and altered pro-inflammatory and anti-inflammatory expression in the hippocampus and amygdala in genes known to be regulated by the glucocorticoid receptor. These changes were associated with increased anxiety behavior, decreased basal corticosterone levels and a slower return to baseline levels following a stress challenge. The data indicate that the dietary environment during development programs glucocorticoid signaling pathways in limbic areas relevant for the regulation of HPA function and anxiety behavior.

Calcium-based dendritic excitability and its regulation in the deep cerebellar nuclei

The deep cerebellar nuclei (DCN) convey the final output of the cerebellum and are a major site of activity-dependent plasticity. Here, using patch-clamp recording and two-photon calcium imaging in rat brain slices, we demonstrate that DCN dendrites exhibit three hallmarks of active amplification of electrical signals. First, they produce calcium transients with rise times of tens of milliseconds, comparable in amplitude and duration to calcium spikes in other neurons. Second, calcium signal amplitudes are undiminished along the length of dendrites to the farthest distances from the soma. Third, they can generate calcium signals even in the presence of tetrodotoxin, a sodium channel blocker that abolishes somatic action potential initiation. DCN calcium transients do require the action of T-type calcium channels, a common voltage-gated conductance in excitable dendrites. Dendritic calcium influx was evoked by release from hyperpolarization, peaked within tens of milliseconds, and was observed in both transient- and weak-rebound-firing neurons. In a survey across the DCN, transient-burst rebound firing, which was accompanied by the most rapid calcium flux, was more common in lateral nucleus than in interpositus nucleus and was not seen in medial nucleus. Rebound firing and calcium transients were not present in animals shipped 1-3 days before recording, a condition associated with elevated maternal and pup corticosterone and reduced pup body weight. Rebounds could be restored by the protein kinase C activator phorbol 12-myristate-13-acetate. Thus local calcium-based dendritic excitability supports a stage of presomatic amplification that is under regulation by stress and neuromodulatory influence.

Ultraviolet crown coloration in female blue tits predicts reproductive success and baseline corticosterone

A growing number of studies provide evidence that female plumage coloration is indicative of individual quality and can influence male mate choice. In blue tits (Cyanistes caeruleus), both sexes exhibit bright ultraviolet (UV)-reflectant crown feathers, which have previously been shown to be attractive to the opposite sex. In males, there is evidence that UV reflectance of the crown feathers is an honest signal of quality in this species, but it is unclear whether this is the case for females. To address this, the UV signal (an index of relative UV reflectance specific to the visual sensitivities of the blue tit) of mothers was measured during brood rearing for 3 years (2008–2010) and related to indices of reproductive success, that is, lay date, clutch size, and number of chicks fledged and maternal state, that is, body condition and baseline corticosterone (CORT). Maternal UV signal was unrelated to clutch size but was positively correlated with number of chicks fledged in 3 years. Maternal UV signal was also negatively correlated with lay date, but this was not consistent across years. In addition, maternal UV signal was negatively correlated with baseline CORT in all years but was not predictive of body condition. Taken together, these results provide evidence that female plumage coloration is indicative of female quality and may serve as a signal for mate choice. Further, it provides novel evidence that maternal baseline CORT is associated with UV plumage signal in free-living birds and may be an important mechanistic link between an individual’s ornamentation, state, and reproductive performance.

Maternal androgen excess reduces placental and fetal weights, increases placental steroidogenesis, and leads to long-term health effects in their female offspring

Here, we tested the hypothesis that excess maternal androgen in late pregnancy reduces placental and fetal growth, increases placental steroidogenesis, and adversely affects glucose and lipid metabolism in adult female offspring. Pregnant Wistar rats were randomly assigned to treatment with testosterone (daily injections of 5 mg of free testosterone from gestational days 16 to 19) or vehicle alone. In experiment 1, fetal and placental weights, circulating maternal testosterone, estradiol, and corticosterone levels, and placental protein expression and distribution of estrogen receptor-α and -β, androgen receptor, and 17β-hydroxysteroid dehydrogenase 2 were determined. In experiment 2, birth weights, postnatal growth rates, circulating testosterone, estradiol, and corticosterone levels, insulin sensitivity, adipocyte size, lipid profiles, and the presence of nonalcoholic fatty liver were assessed in female adult offspring. Treatment with testosterone reduced placental and fetal weights and increased placental expression of all four proteins. The offspring of testosterone-treated dams were born with intrauterine growth restriction; however, at 6 wk of age there was no difference in body weight between the offspring of testosterone- and control-treated rats. At 10-11 wk of age, the offspring of the testosterone-treated dams had less fat mass and smaller adipocyte size than those born to control rats and had no difference in insulin sensitivity. Circulating triglyceride levels were higher in the offspring of testosterone-treated dams, and they developed nonalcoholic fatty liver as adults. We demonstrate for the first time that prenatal testosterone exposure alters placental steroidogenesis and leads to dysregulation of lipid metabolism in their adult female offspring.

Maternal corticosterone regulates nutrient allocation to fetal growth in mice

Stresses during pregnancy that increase maternal glucocorticoids reduce birth weight in several species. However, the role of natural glucocorticoids in the mother in fetal acquisition of nutrients for growth remains unknown. This study aimed to determine whether fetal growth was reduced as a consequence of altered amino acid supply when mice were given corticosterone in their drinking water for 5 day periods in mid to late pregnancy (day, D, 11-16 or D14-19). Compared to controls drinking tap water, fetal weight was always reduced by corticosterone. At D16, corticosterone had no effect on materno-fetal transfer of [(14)C]methylaminoisobutyric acid (MeAIB), although placental MeAIB accumulation and expression of the Slc38a1 and Slc38a2 transporters were increased. However, at D19, 3 days after treatment ended, materno-fetal transfer of MeAIB was increased by 37% (P < 0.04). During treatment at D19, placental accumulation and materno-fetal transfer of MeAIB were reduced by 40% (P < 0.01), although expression of Slc38a1 was again elevated. Permanent reductions in placental vascularity occurred during the earlier but not the later period of treatment. Placental Hsd11b2 expression, which regulates feto-placental glucocorticoid bioavailability, was also affected by treatment at D19 only. Maternal corticosterone concentrations inversely correlated with materno-fetal MeAIB clearance and fetal weight at D19 but not D16. On D19, weight gain of the maternal carcass was normal during corticosterone treatment but reduced in those mice treated from D11 to D16, in which corticosterone levels were lowest. Maternal corticosterone is, therefore, a physiological regulator of the amino acid supply for fetal growth via actions on placental phenotype.

Sex-specific offspring growth according to maternal testosterone, corticosterone, and glucose levels

Sex allocation theory in vertebrates has greatly benefited from the recent advances in studies on the physiological mechanisms of birth sex ratio variation (e.g., maternal glucose, stress, and testosterone levels). The same physiological mechanisms may, however, also mediate permanent sex-specific effects on individuals after birth. Together with biased maternal postpartum investment on sex allocation, they can have long-term fitness consequences for the offspring. We studied whether maternal preconception levels of serum glucose and testosterone, and fecal corticosterone metabolites differently influenced male and female pup weight until weaning in field voles (Microtus agrestis). In this species, high maternal preconception serum glucose and testosterone levels have previously been associated with the excess of male pups at birth. Our results suggest that male, but not female, pup weight increases with higher maternal preconception testosterone level whereas high maternal serum glucose level promoted female pup weight only. The level of maternal fecal corticosterone metabolites was not related to pup weight in either sex. These findings suggest that in field voles the same physiological mechanisms influencing sex ratio at birth may also influence offspring postnatal weight; however, such influences can act in conflict, as seen in the case of maternal glucose level.

Caffeine-Induced Activated Glucocorticoid Metabolism in the Hippocampus Causes Hypothalamic-Pituitary-Adrenal Axis Inhibition in Fetal Rats

Epidemiological investigations have shown that fetuses with intrauterine growth retardation (IUGR) are susceptible to adult metabolic syndrome. Clinical investigations and experiments have demonstrated that caffeine is a definite inducer of IUGR, as children who ingest caffeine-containing food or drinks are highly susceptible to adult obesity and hypertension. Our goals for this study were to investigate the effect of prenatal caffeine ingestion on the functional development of the fetal hippocampus and the hypothalamic-pituitary-adrenal (HPA) axis and to clarify an intrauterine HPA axis-associated neuroendocrine alteration induced by caffeine. Pregnant Wistar rats were intragastrically administered 20, 60, and 180 mg/kg·d caffeine from gestational days 11–20. The results show that prenatal caffeine ingestion significantly decreased the expression of fetal hypothalamus corticotrophin-releasing hormone. The fetal adrenal cortex changed into slight and the expression of fetal adrenal steroid acute regulatory protein (StAR) and cholesterol side-chain cleavage enzyme (P450scc), as well as the level of fetal adrenal endogenous corticosterone (CORT), were all significantly decreased after caffeine treatment. Moreover, caffeine ingestion significantly increased the levels of maternal and fetal blood CORT and decreased the expression of placental 11β-hydroxysteroid dehydrogenase-2 (11β-HSD-2). Additionally, both in vivo and in vitro studies show that caffeine can downregulate the expression of fetal hippocampal 11β-HSD-2, promote the expression of 11β-hydroxysteroid dehydrogenase 1 and glucocorticoid receptor (GR), and enhance DNA methylation within the hippocampal 11β-HSD-2 promoter. These results suggest that prenatal caffeine ingestion inhibits the development of the fetal HPA axis, which may be associated with the fetal overexposure to maternal glucocorticoid and activated glucocorticoid metabolism in the fetal hippocampus. These results will be beneficial in elucidating the developmental toxicity of caffeine and in exploring the fetal origin of adult HPA axis dysfunction and metabolic syndrome susceptibility for offspring with IUGR induced by caffeine.

Maternal Corticosterone Exposure in the Mouse Has Sex-Specific Effects on Placental Growth and mRNA Expression

Maternal exposure to increased synthetic glucocorticoids (GC) during pregnancy is known to disturb fetal development and increase the risk of long-term disease. Maternal exposure to elevated levels of natural GC is likely to be common yet is relatively understudied. The placenta plays an important role in regulating fetal exposure to maternal GC but is itself vulnerable to maternal insults. This study uses a mouse model of maternal corticosterone (Cort) exposure to investigate its effects on the developing placenta. Mice were treated with Cort (33 μg/kg·h) for 60 h starting at embryonic d 12.5 (E12.5) before collection of placentas at E14.5 and E17.5. Although Cort exposure did not affect fetal size, placentas of male fetuses were larger at E17.5 in association with changes in placental Igf2. This increase in size was associated with an increase in placental thickness and an increase in placental junctional zone volume. Placentas from female fetuses were of normal size and had no changes in growth factor mRNA levels. The expression of the protective enzyme 11β-hydroxysteroid dehydrogenase type 2 was increased at E14.5 but was decreased in males at E17.5. In contrast, the expression of Nr3c1 (which encodes the GC receptor) was increased during the Cort exposure and remained elevated at E17.5 in the placentas of male fetuses. Our study has shown that maternal Cort exposure infers a sex-specific alteration to normal placental growth and growth factor expression, thus further adding to our understanding of the mechanisms of male dominance of programmed disease.

Neonatal exposure to low dose corticosterone persistently modulates hippocampal mineralocorticoid receptor expression and improves locomotor/exploratory behaviour in a mouse model of Rett syndrome

Rett syndrome (RTT) is a pervasive neurodevelopmental disorder, primarily affecting girls. RTT causes a wide variety of debilitating symptoms and no cure currently exists. Mouse models bearing mutations in the Mecp2 gene recapitulate most physiological and behavioural RTT-related abnormalities. Stimulating neonatal environments (e.g. brief maternal separations or maternal low-dose corticosterone supplementation) reduce stress and fear responses at adulthood. The present study investigated whether impacting early in development the hypothalamic-pituitary-adrenal axis, by exposing Mecp2-308 mutant pups to a low dose of corticosterone (50 µg/ml, during the 1st week of life) may contrast RTT-related abnormalities in neuroendocrine regulation and behavioural adaptation at adulthood. In line with previous reports, when fully symptomatic, MeCP2-308 mice showed a reduction in the regular nocturnal hyperactivity in the home-cage and increased anxiety-like behaviours and plasma corticosterone (CORT) levels in response to restraint stress. An abnormal elevation in mRNA levels of mineralocorticoid receptors (MR) and BDNF gene was also evident in the hippocampus of fully symptomatic mutant mice. Neonatal CORT modulated MR gene expression and behavioural reactivity towards a novel object, also restoring wt-like levels of locomotor/exploratory behaviour in mutant mice. Enhanced sensitivity to the neonatal treatment (in terms of increase in GR and MR mRNA levels), was also evident in the hippocampus of MeCP2-308 mice compared to wt littermates. Present results corroborate the hypothesis that targeting the glucocorticoid system may prove valid in contrasting at least some of the RTT-related symptoms and provide evidence that pharmacological interventions during critical early time windows can persistently improve the behavioural phenotype of RTT mice. Current data also support the emerging role played by Mecp2 in mediating the epigenetic programming induced by early life events and indicate that, in the absence of functional MeCP2, programming of the central nervous system in response to early environmental stimuli is abnormally regulated.This article is part of the Special Issue entitled ‘Neurodevelopmental Disorders’.

Maternal corticosterone is transferred into the egg yolk

Hormones deposited in the avian egg are considered in many studies to influence or to adjust offspring phenotype to prevailing conditions in an adaptive way. Several studies demonstrated an effect of corticosterone, the main glucocorticoid in birds, injected into the egg on the developing chick, but the injection of steroids in the egg is far from mimicking the natural distribution of the hormone in the egg. Other studies applied a stressor or corticosterone to the mother. However it is still debated whether an increase of circulating corticosterone in the mother translates into higher concentrations of corticosterone in the egg. Therefore, we investigated in captive barn owls Tyto alba whether circulating corticosterone in egg-laying females elevated within a physiological range, resulted in the deposition of corticosterone in eggs. We found that an increase in circulating corticosterone in the mother within the naturally occurring range translated into elevated concentrations of corticosterone in the yolk of subsequently laid eggs, indicating a specific time frame and yolk layer of corticosterone deposition. We conclude that increasing maternal plasma corticosterone within a naturally occurring range is an efficient tool to increase corticosterone concentration in the egg and to manipulate conditions for the developing embryo.

Do Gravid Females Become Selfish? Female Allocation of Energy during Gestation

Net energy availability depends on plasma corticosterone concentrations, food availability, and their interaction. Limited net energy availability requires energy trade-offs between self-maintenance and reproduction. This is important in matrotrophic viviparous animals because they provide large amounts of energy for embryos, as well as self-maintenance, for the extended period of time during gestation. In addition, gravid females may transmit environmental information to the embryos in order to adjust offspring phenotype. We investigated effects of variation in maternal plasma corticosterone concentration and maternal food availability (2 × 2 factorial design) during gestation on offspring phenotype in a matrotrophic viviparous lizard (Pseudemoia entrecasteauxii). Subsequently, we tested preadaptation of offspring phenotype to their postnatal environment by measuring risk-averse behavior and growth rate using reciprocal transplant experiments. We found that maternal net energy availability affected postpartum maternal body condition, offspring snout-vent length, offspring mass, offspring performance ability, and offspring fat reserves. Females treated with corticosterone allocated large amounts of energy to their own body condition, and their embryos allocated more energy to energy reserves than somatic growth. Further, offspring from females in high plasma corticosterone concentration showed compensatory growth. These findings suggest that while females may be selfish when gestation conditions are stressful, the embryos may adjust their phenotype to cope with the postnatal environment.

Maternal obesity in the rat programs male offspring exploratory, learning and motivation behavior: prevention by dietary intervention pre-gestation or in gestation

We studied the effects of maternal high fat diet (HFD, 25% calories from fat administered before and during pregnancy and lactation) and dietary intervention (switching dams from HFD to control diet) at different periconceptional periods on male offspring anxiety related behavior, exploration, learning, and motivation. From weaning at postnatal day (PND) 21, female subjects produced to be the mothers in the study received either control diet (CTR – 5% calories from fat), HFD through pregnancy and lactation (MO), HFD during PNDs 21–90 followed by CTR diet (pre-gestation (PG) intervention) or HFD from PND 21 to 120 followed by CTR diet (gestation and lactation (G) intervention) and bred at PND 120. At 19 days of gestation maternal serum corticosterone was increased in MO and the PG and G dams showed partial recovery with intermediate levels. In offspring, no effects were found in the elevated plus maze test. In the open field test, MO and G offspring showed increase zone entries, displaying less thigmotaxis; PG offspring showed partial recuperation of this behavior. During initial operant conditioning MO, PG and G offspring displayed decreased approach behavior with subsequent learning impairment during the acquisition of FR-1 and FR-5 operant conditioning for sucrose reinforcement. Motivation during the progressive ratio test increased in MO offspring; PG and G intervention recuperated this behavior. We conclude that dietary intervention can reverse negative effects of maternal HFD and offspring outcomes are potentially due to elevated maternal corticosterone.

Elevated Plasma Corticosterone Decreases Yolk Testosterone and Progesterone in Chickens: Linking Maternal Stress and Hormone-Mediated Maternal Effects

Despite considerable research on hormone-mediated maternal effects in birds, the underlying physiology remains poorly understood. This study investigated a potential regulation mechanism for differential accumulation of gonadal hormones in bird eggs. Across vertebrates, glucocorticoids can suppress reproduction by downregulating gonadal hormones. Using the chicken as a model species, we therefore tested whether elevated levels of plasma corticosterone in female birds influence the production of gonadal steroids by the ovarian follicles and thus the amount of reproductive hormones in the egg yolk. Adult laying hens of two different strains (ISA brown and white Leghorn) were implanted subcutaneously with corticosterone pellets that elevated plasma corticosterone concentrations over a period of nine days. Steroid hormones were subsequently quantified in plasma and yolk. Corticosterone-implanted hens of both strains had lower plasma progesterone and testosterone levels and their yolks contained less progesterone and testosterone. The treatment also reduced egg and yolk mass. Plasma estrogen concentrations decreased in white Leghorns only whereas in both strains yolk estrogens were unaffected. Our results demonstrate for the first time that maternal plasma corticosterone levels influence reproductive hormone concentrations in the yolk. Maternal corticosterone could therefore mediate environmentally induced changes in yolk gonadal hormone concentrations. In addition, stressful situations experienced by the bird mother might affect the offspring via reduced amounts of reproductive hormones present in the egg as well as available nutrients for the embryo.

Dexamethasone induces fetal developmental toxicity through affecting the placental glucocorticoid barrier and depressing fetal adrenal function

This study evaluates the neuroendocrine-interference mechanism underlying dexamethasone-induced developmental toxicity. Pregnant mice were treated with various doses of dexamethasone (0, 0.5, 2.0 and 8.0 mg/kg), corticosterone levels in maternal serum, mRNA expressions of maternal and fetal adrenal steroidogenic acute regulatory protein (StAR), cytochrome P450 responsible for cholesterol side chain cleavage (P450scc) and placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2) were measured. And the expressions of StAR and P450scc were also measured in cultured primary human fetal adrenocortical cells treated with various concentrations of dexamethasone (0, 1, 10 and 100 μmol/L) for 24 h. Mice suffered from intrauterine growth retardation (IUGR) after exposure to dexamethasone. The IUGR rate was augmented to 42.9% and 95.7% in 2.0 and 8.0 mg/kg dexamethasone groups, respectively ( P < 0.01). The level of maternal serum corticosterone in three dexamethasone groups were decreased to 31.8%, 34.8% and 32.9%, respectively ( P < 0.05 or P < 0.01), as compared with the control. Furthermore, the mRNA expressions of maternal and fetal adrenal StAR and P450scc in 8.0 mg/kg dexamethasone groups were decreased to 19.3% and 10.8%, 11.0% and 9.9% of that in the corresponding controls, respectively ( P < 0.05). The mRNA expressions of placental 11β-HSD-2 were dose-dependently reduced in dexamethasone groups, particularly, the mRNA decreased to 22.2% in 8.0 mg/kg dexamethasone group, as compared with the control ( P = 0.15). No obvious changes of StAR and P450scc in vitro after dexamethasone treatment. These suggest that prenatal dexamethasone exposure induces fetal developmental toxicity. A possible underlying mechanism is that dexamethasone may affect the placental glucocorticoid barrier and depressing fetal adrenal function.

Gestational and postpartum corticosterone exposure to the dam affects behavioral and endocrine outcome of the offspring in a sexually-dimorphic manner

Exposure to high levels of glucocorticoids in utero and during the postpartum period has a detrimental effect on brain development. We created an animal model of postpartum stress/depression based on administering high levels of corticosterone (CORT) to the dams during the postpartum period which caused behavioral changes and reduced hippocampal cell proliferation in the offspring. As the consequences of early exposure to glucocorticoids may depend on the dose and the developmental stage of the offspring, the present study was conducted to investigate the effects of low (10 mg/kg) or high levels of CORT (40 mg/kg) given to dams either during gestation, postpartum or across both gestation and postpartum on the outcome of the offspring. Male and female offspring were weighed throughout the experiment, tested in a series of behavioral tests (forced swim test, open field, elevated plus maze) and basal and restraint stress CORT levels were examined in adolescence or young adulthood. Results show that maternal CORT exposure, regardless of when administered, significantly attenuated body weight gain until adulthood in the offspring. Offspring exposed to low maternal CORT, but not high maternal CORT, during the postpartum had higher basal levels of CORT as young adults. Further, male and female offspring of dams exposed to high maternal CORT in utero showed more depressive-like behavior in the forced swim test, while males of dams exposed to high maternal CORT postpartum exhibited more anxiety-like behavior in the elevated plus maze. Taken together, maternal glucocorticoid exposure have long lasting effects on male and female offspring’s behavioral and neuroendocrine measures in adolescence and adulthood depending on the time of exposure to glucocorticoids.This article is part of a Special Issue entitled ‘Anxiety and Depression’.

Effects of neonatal methamphetamine treatment on adult stress-induced corticosterone release in rats

In rats, neonatal (+)-methamphetamine (MA) exposure and maternal separation stress increase corticosterone during treatment and result in learning and memory impairments later in life. Early-life stress also changes later responses to acute stress. We tested the hypothesis that neonatal MA exposure would alter adult corticosterone after acute stress or MA challenge. Rats were treated with MA (10mg/kg×4/day), saline, or handling on postnatal (P) days 11–15 or 11–20 (days that lead to learning and memory impairments at this dose). As adults, corticosterone was measured before and after 15min forced swim (FS) or 15min forced confinement (FC), counterbalanced, and after an acute MA challenge (10mg/kg) given last. FS increased corticosterone more than FC; order and stress type interacted but did not interact with treatment; treatment interacted with FS but not with FC. In the P11-15 regimen, MA-treated rats showed more rapid increases in corticosterone after FS than controls. In the P11-20 regimen, MA-treated rats showed a trend toward more rapid decrease in corticosterone after FS. No differences were found after MA challenge. The data do not support the hypothesis that neonatal MA causes changes in adult stress responsiveness to FS, FC, or an acute MA challenge.

Circadian Variation in Placental and Hepatic Clock Genes in Rat Pregnancy

Clock genes drive circadian rhythms in a range of physiological processes both centrally and in peripheral tissues such as the liver. The aims of this study were to determine whether the two functionally-distinct zones of the rat placenta (junctional and labyrinth) differentially express clock genes and, if so, whether these exhibit circadian patterns. Rats were sampled from d 21 of pregnancy (term = d 23) and from diestrus I of the estrous cycle. Adult liver (all animals), fetal liver, and placental zones (pregnant animals) were collected at 0800, 1400, 2000, and 0200 h. Both zones of the rat placenta expressed all seven canonical clock genes (Clock, Bmal1, Per1, Per2, Per3, Cry1, and Cry2), but there were marked zonal differences and, unlike in maternal liver, circadian variation in placenta was limited. Similarly, placental expression of Vegf varied with zone but not time of day. Pregnancy also led to marked changes in hepatic clock gene expression, with peak levels of Per1, Cry1, and Cry2 all reduced, Per3 increased, and circadian variation in Clock expression lost. All clock genes were expressed in fetal liver, but there was less circadian variation than in maternal liver. Similarly, fetal corticosterone levels remained stable across the day, whereas maternal corticosterone showed clear circadian variation. In conclusion, our data show that the rat placenta expresses all canonical clock genes in a highly zone-specific manner but with relatively little circadian variation. Moreover, pregnancy alters the expression and circadian variation of clock genes in maternal liver, possibly contributing to maternal physiological adaptations.

Evidence for placental transfer of maternal corticosterone in a viviparous lizard

In mammals, there is experimental evidence that circulating maternal cortisol is transferred to the embryos across the placenta during gestation. Direct effects of this maternal cortisol may allow embryos to display phenotypic plasticity to cope with postnatal environments (i.e., pre-programming). The potential for maternal hormone induced-adaptation may be of considerable evolutionary significance in viviparous animals. However, to date, there is no such direct evidence that circulating maternal corticosterone passes through the placenta and into the embryos of viviparous reptiles. In this study, we assessed the transfer of 3H-corticosterone injected into females of the lizard Pseudemoia entrecasteauxii into maternal blood, maternal liver, the embryo, the yolk and the amniotic fluid during mid-to-late gestation. We provide direct evidence that circulating maternal corticosterone passes through the placenta into the embryos in this species. Transfer of maternal corticosterone into the embryos significantly decreased at the end of embryonic development. We discuss these results in terms of the relationships between the degree of corticosterone transfer and embryonic stage. These results demonstrate the potential for direct effects of maternal corticosterone, including endocrine pre-programming, upon the developing embryos in viviparous lizards.

Effect of maternal corticosterone on utilisation of residual yolk sac fatty acids by developing broiler embryo

1. Increased concentrations of maternal corticosterone are deposited into egg yolk under stress conditions. This experiment investigated the effect of maternal corticosterone on yolk and yolk sac fatty acid profiles of eggs and developing broiler embryos. 2. At 42 weeks of age, 200 broiler breeder females were randomly divided into two groups: maternal corticosterone (MC): 2 mg/hen/d of corticosterone dissolved in 1 mL of 99% ethanol and mixed in the individual daily feed for a 14 d period, and control: 1 mL of ethanol added to the individual daily feed. Hens were inseminated, and eggs were collected daily from d 3 of corticosterone feeding to d 14 and incubated. Fatty acid profiles of egg yolk and yolk sac were analysed before incubation and at 12, 14, 18 and 21 d of incubation. 3. Yolk corticosterone concentrations were greater in MC eggs. Before incubation, eggs from MC had lower DHA (22 : 6 n-3) but higher stearic (18 : 0) and dihomo-gamma linolenic (20 : 3 n-6 Cis 8,11,14) acid content compared with the control. 4. Higher concentrations of stearic (18 : 0), elaidic (18 : 1 tr n-9), eicosenoic (20 : 1 n-9), eicosadienoic (20 : 2 n-6), dihomo-gamma linoleic (20 : 3 n-6) and arachidonic (20 : 4 n-6) acids and lower concentrations of myristic (14 : 0), palmitoleic (16 : 1 n-7), linoleic (18 : 2 n-6) and DHA (22 : 6 n-3) were found at different periods of incubation in the residual yolk sac of MC than from controls. 5. The results suggest that the preferentially selective absorption of fatty acids is related to specific tissue requirements.

Effects of maternal l-tryptophan depletion and corticosterone administration on neurobehavioral adjustments in mouse dams and their adolescent and adult daughters

Major depressive disorder (MDD), a pathology characterized by mood and neurovegetative disturbances, depends on a multi-factorial contribution of individual predisposition (e.g., diminished serotonergic transmission) and environmental factors (e.g., neonatal abuse or neglect). Despite its female-biased prevalence, MDD basic research has mainly focused on male rodents. Most of present models of depression are also devalued due to the fact that they typically address only one of the aforementioned pathogenetic factors. In this paper we first describe the basic principles behind mouse model development and evaluation and then articulate that current models of depression are intrinsically devalued due to poor construct and/or external validity. We then report a first attempt to overcome this limitation through the design of a mouse model in which the genetic and the environmental components of early risk factors for depression are mimicked together. Environmental stress is mimicked through the supplementation of corticosterone in the maternal drinking water while biological predisposition is mimicked through maternal access to an L-tryptophan (the serotonin precursor) deficient diet during the first week of lactation. CD1 dams and their offspring exposed to the L-tryptophan deficient diet (T) and to corticosterone (80mg/l; C) were compared to animal facility reared (AFR) subjects. T and C mice served as intermediate reference groups. Adolescent TC offspring, compared to AFR mice, showed decreased time spent floating in the forced-swim test and increased time spent in the open sectors of an elevated 0-maze. Adult TC offspring showed reduced preference for novelty, decreased breakpoints in the progressive ratio operant procedure and major alterations in central BDNF levels and altered HPA regulation. The route of administration and the possibility to control the independent variables predisposing to depressive-like symptoms disclose novel avenues towards the development of animal models with increased external and construct validity. Furthermore, the observation that, compared to adult subjects, adolescent mice display an opposite profile suggests that peri-pubertal developmental processes may interact with neonatal predispositions to calibrate the adult abnormal phenotype.