hpa and fetus in animals

Fetal neonatal alloimmune thrombocytopenia (FNAIT) is a devastating bleeding disorder in the fetus or neonate caused by transplacental transport of maternal alloantibodies to paternal-derived antigen on fetal platelets. In Caucasians, up to 80% of FNAIT cases result from maternal immunization to human platelet antigen (HPA)-1a. New methods have developed facilitating detection of common and private antibodies against HPAs triggering FNAIT. Understanding the pathogenesis of FNAIT made it possible to develop a novel strategy to treat this disorder...

Imbalanced maternal nutrition during gestation can cause alterations of the hypothalamic-pituitary-adrenal (HPA) system in offspring. The present study investigated the effects of maternal low- and high-protein diets during gestation in pigs on the maternal-fetal HPA regulation and expression of the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), 11β-hydroxysteroid dehydrogenase 1 and 2 (11β-HSD1 and 11β-HSD2) and c-fos mRNAs in the placenta and fetal brain. Twenty-seven German Landrace sows were fed diets with high (HP, 30%), low (LP, 6...

This paper considers the transgenerational effects of prenatal stress of different etiology. The impacts of stress factors on the biochemical and morphofunctional parameters of life of the mother, fetus, and offspring in the first and subsequent generations (F1-F4) are estimated. Particular attention is paid to assessing changes in the parameters of physical development, the state of the hypothalamic-pituitary-adrenal axis, proinflammatory status, behavioral indicators, cognitive performance, and vegetative balance in the post-stress period...

Low birthweight, a marker of an adverse in utero environment, is associated with cardiometabolic disease and brain disorders in adulthood. The adaptive changes made by the fetus in response to the intra-uterine environment result in permanent changes in physiology, structure and metabolism, a phenomenon termed early life programming. One of the key hypotheses to explain programming, namely over exposure of the developing fetus to glucocorticoids, was proposed nearly two decades ago, following the observation that the fetus was protected from high glucocorticoid levels in the mother by the actions of the placental barrier enzyme, 11β-hydroxysteroid dehydrogenase, which converts active glucocorticoids into inactive products...

The 'thrifty phenotype' hypothesis proposes that the fetus adapts to an adverse intrauterine milieu by optimizing the use of a reduced nutrient supply to ensure survival, but by favoring the development of certain organs over that of others, this leads to persistent alterations in the growth and function of developing tissues. This concept has been somewhat controversial, however recent epidemiological, clinical, and animal studies provide support for the developmental origins of disease hypothesis. Underlying mechanisms include reprogramming of the hypothalamic-pituitary-adrenal axis, islet development, and insulin signaling pathways...

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...

The hypothalamic-pituitary-adrenocortical (HPA) axis is a major neuroendocrine pathway that modulates the stress response. The glucocorticoid, cortisol, is the principal end product of the HPA axis in humans and plays a fundamental role in maintaining homeostasis and in fetal maturation and development. Antenatal administration of synthetic glucocorticoids (GCs) accelerates fetal lung maturation and has significantly decreased neonatal mortality and morbidity in infants born before 34 weeks of gestation. Exposure to excess levels of endogenous GCs and exogenous GCs (betamethasone and dexamethasone) has been shown to alter the normal development trajectory...

By late gestation, the maturing hypothalamo-pituitary-adrenal (HPA) axis aids the fetus in responding to stress. Hypoxia represents a significant threat to the fetus accompanying situations such as preeclampsia, smoking, high altitude, and preterm labor. We developed a model of high-altitude (3,820 m), long-term hypoxia (LTH) in pregnant sheep. We describe the impact of LTH on the fetal HPA axis at the level of the hypothalamic paraventricular nucleus (PVN), anterior pituitary corticotrope, and adrenal cortex...

Epidemiological studies have shown that small size at birth is associated with an increased risk of coronary heart disease and its risk factors, including hypertension and Type 2 diabetes.It is suggested that these observations linking low birthweight with disease result from an imbalance between fetal nutrient demand and supply. This imbalance results in metabolic and endocrine adaptations, which benefit the fetus in the short term by reducing fetal growth and increasing fuel availability, but in the longer term they are maladaptive leading to an increased risk of coronary heart disease...

Fetuses with intrauterine growth retardation (IUGR) induced by prenatal nicotine exposure are susceptible to adult metabolic syndrome. Our goals for this study were to investigate the effects of prenatal nicotine exposure on the fetal hypothalamic-pituitary-adrenal (HPA) axis and glucose and lipid metabolism and to explain the susceptibility to adult metabolic syndrome for fetuses with nicotine induced-IUGR. Pregnant Wistar rats were administered 0.25, 0.5, and 1.0 mg/kg nicotine subcutaneously twice a day from gestational day 11 to 20...

Neonatal alloimmune thrombocytopenia (NAIT) is caused by fetomaternal platelet incompatibility with maternal antibodies crossing the placenta and destroying fetal platelets. Antibodies against human platelet antigen-1a (HPA-1a) and HPA-5b are responsible for the majority of NAIT cases. We observed a suspected NAIT in a newborn with a platelet count of 25 G/l and petechial haemorrhages. Serological analysis of maternal serum revealed an immunisation against αIIbβ3 on paternal platelets only, indicating the presence of an antibody against a new rare alloantigen (Sec(a)) residing on αIIbβ3...

Fetal glucocorticoid exposure is a key mechanism proposed to underlie prenatal 'programming' of adult affective behaviours such as depression and anxiety. Indeed, the glucocorticoid metabolising enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which is highly expressed in the placenta and the developing fetus, acts as a protective barrier from the high maternal glucocorticoids which may alter developmental trajectories. The programmed changes resulting from maternal stress or bypass or from the inhibition of 11β-HSD2 are frequently associated with alterations in the hypothalamic-pituitary-adrenal (HPA) axis...

Melanocortins, adrenocorticotropic hormone (ACTH) and α-, β-, and γ-melanocyte-stimulating hormone (MSH) are produced in the placenta and secreted into embryos/fetuses. ACTH concentrations are higher in fetal plasma than in maternal plasma and peak at mid-gestation in rats, whereas ACTH production starts in the anterior lobe of the fetal pituitary at later stages. Melanocortin receptors (MC1-5R), receptors for ACTH and α-, β- and γ-MSH, are expressed in various adult organs. The specific function of these receptors has been well examined in the hypothalamic-pituitary-adrenocortical (HPA) axis and the HPA axis-like network in the skin, and anti-inflammatory effects for white blood cells have also been investigated...

The fetus may be exposed to increased endogenous or synthetic glucocorticoid (GS) exposure in late gestation. Approximately 7% of pregnant women in Europe and North America are treated with synthetic GSs to promote lung maturation in fetuses at risk of preterm delivery. Maternal steroid treatment before preterm delivery is one of the best documented and most cost effective life saving treatments in prenatal medicine but, in certain circumstances, the price of accelerated lung maturity may be loss of brain cells, increased neurodevelopmental disability, intra-uterine growth restriction (IUGR), and an increased risk of preterm delivery, of programming of post-natal hypertension, and of increased post-natal activity in the hypothalamo-pituitary-adrenal (HPA) axis...

BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a bleeding disorder caused by transplacental passage of maternal antibodies to fetuses whose platelets (PLTs) express the corresponding human PLT antigen (HPA). STUDY DESIGNS AND METHODS: We observed a fetus with FNAIT who died from a severe intracranial hemorrhage. Analysis of maternal serum in antigen capture assay with paternal PLTs showed reactivity with PLT glycoprotein (GP)IIb/IIIa (α(IIb) β(3) ) and GPIa/IIa (α(2) β(1) integrin), indicating the presence of anti-HPA-1a and an additional alloantibody against GPIa (termed anti-Swi(a) )...

The present study examined the effect of prenatal stress in rats from days 13-20 of gestation on anxiogenic behaviour in the elevated plus maze (EPM) together with changes in the gene expression of corticotrophin-releasing hormone (CRH), its receptors, CRHR1 and CRHR2, as well as CRH binding protein (CRH-BP) in the paraventricular nucleus (PVN) and amygdala of their male and female offspring. Both prenatally-stressed (PS) males and females showed heightened anxiety in the EPM. Prenatal stress did not alter the gene expression of CRH or its receptors in the male PVN, although it decreased CRH-BP mRNA, which could augment the activity of free CRH...

The major changes in highly dynamic neuroendocrine systems that are essential for establishing and maintaining pregnancy are outlined from studies on rodents. These changes optimise the internal environment to provide the life support system for the placenta, embryo and fetus. These include automatic prevention of further pregnancy, blood volume expansion, increased appetite and energy storage. The brain regulates these changes, in response to steroid (estrogens, progesterone) and peptide (lactogens, relaxin) hormone signals...

BACKGROUND: Lung maturation is modulated by several factors, including glucocorticoids. Expression of hypothalamic-pituitary-adrenal (HPA) axis-related components, with proposed or described local regulatory systems analogous to the HPA axis, was reported in peripheral tissues. Here, HPA axis-related genes were studied in the mouse developing lung during a period overlapping the surge of surfactant production. METHODS: Expression of genes encoding for corticotropin-releasing hormone (CRH), CRH receptors (CRHR) 1 and 2beta, CRH-binding protein, proopiomelanocortin (POMC), melanocortin receptor 2 (MC2R), and glucocorticoid receptor was quantified by real-time PCR and localized by in situ hydridization in fetal lungs at gestational days (GD) 15...

Maternal dietary protein restriction during pregnancy is associated with low fetal birth weight and leads to renal morphological and physiological changes. Different mechanisms can contribute to this phenotype: exposure to fetal glucocorticoid, alterations in the components of the renin-angiotensin system, apoptosis, and DNA methylation. A low-protein diet during gestation decreases the activity of placental 11ß-hydroxysteroid dehydrogenase, exposing the fetus to glucocorticoids and resetting the hypothalamic-pituitary-adrenal axis in the offspring...

The hypothalamic-pituitary-adrenal (HPA) axis plays a key role in the neuroendocrine response to stress. Dynamic changes in HPA axis regulation and hence HPA responsivity occur over the lifetime of an animal. This article focuses on two extremes of the spectrum. The first occurs naturally during pregnancy when stress responses are dampened. The second, at the opposite end of the scale, occurs in offspring of mothers who were exposed to stress during pregnancy and display exaggerated HPA axis stress responses...