Search Results (6)

Background: The term “fetal programming” refers to the effects of endogenous and exogenous corticosteroids, whether received from the mother or the fetus, on brain development and the hypothalamic–pituitary–adrenal axis reset. The authors of this narrative review examine the WHO’s guidelines for prenatal corticosteroids in pregnant women who are at high risk of premature delivery. These guidelines are regarded as the best available for preventing late-life problems resulting from preterm. Methods: In order to find full-text publications published in peer-reviewed journals between 1990 and 2023 that were written in English, the authors searched PubMed, Scopus, Cochrane Library, and Web of Science. Results: The authors highlight the possible adverse long-term effects of prenatal corticosteroid medication on human brain development and function. This pharmacological feature is therapeutically significant because there is less evidence in the scientific literature regarding the potential role that the timing, mode, and dosage of exogenous steroid treatment may have in neurological illnesses down the road. Conclusions: The authors expect that these studies will shed light on the relationship between specially designed prenatal corticosteroid therapy and the molecular mechanisms underlying the prenatal programming of neurodevelopment in childhood and adulthood. Full article

Although the rate of preterm birth has increased in recent decades, a number of preterm infants have escaped death due to improvements in perinatal and neonatal care. Antenatal glucocorticoid (GC) therapy has significantly contributed to progression in lung maturation; however, its potential effects on other organs remain controversial. Furthermore, the effects of antenatal GC therapy on the fetal heart show both pros and cons. Translational research in animal models indicates that constant fetal exposure to antenatal GC administration is sufficient for lung maturation. We have established a premature fetal rat model to investigate immature cardiopulmonary functions in the lungs and heart, including the effects of antenatal GC administration. In this review, we explain the mechanisms of antenatal GC actions on the heart in the fetus compared to those in the neonate. Antenatal GCs may contribute to premature heart maturation by accelerating cardiomyocyte proliferation, angiogenesis, energy production, and sarcoplasmic reticulum function. Additionally, this review specifically focuses on fetal heart growth with antenatal GC administration in experimental animal models. Moreover, knowledge regarding antenatal GC administration in experimental animal models can be coupled with that from developmental biology, with the potential for the generation of functional cells and tissues that could be used for regenerative medical purposes in the future. Full article

Preterm birth coincides with a key developmental window of cardiac growth and maturation, and thus has the potential to influence long-term cardiac function. Individuals born preterm have structural cardiac remodelling and altered cardiac growth and function by early adulthood. The evidence linking preterm birth and cardiovascular disease in later life is mounting. Advances in the perinatal care of preterm infants, such as glucocorticoid therapy, have improved survival rates, but at what cost? This review highlights the short-term and long-term impact of preterm birth on the structure and function of the heart and focuses on the impact of antenatal and postnatal glucocorticoid treatment on the immature preterm heart. Full article

Bronchopulmonary dysplasia (BPD) is the most common respiratory disorder among infants born extremely preterm. The pathogenesis of BPD involves multiple prenatal and postnatal mechanisms affecting the development of a very immature lung. Their combined effects alter the lung’s morphogenesis, disrupt capillary gas exchange in the alveoli, and lead to the pathological and clinical features of BPD. The disorder is ultimately the result of an aberrant repair response to antenatal and postnatal injuries to the developing lungs. Neonatology has made huge advances in dealing with conditions related to prematurity, but efforts to prevent and treat BPD have so far been only partially effective. Seeing that BPD appears to have a role in the early origin of chronic obstructive pulmonary disease, its prevention is pivotal also in long-term respiratory outcome of these patients. There is currently some evidence to support the use of antenatal glucocorticoids, surfactant therapy, protective noninvasive ventilation, targeted saturations, early caffeine treatment, vitamin A, and fluid restriction, but none of the existing strategies have had any significant impact in reducing the burden of BPD. New areas of research are raising novel therapeutic prospects, however. For instance, early topical (intratracheal or nebulized) steroids seem promising: they might help to limit BPD development without the side effects of systemic steroids. Evidence in favor of stem cell therapy has emerged from several preclinical trials, and from a couple of studies in humans. Mesenchymal stromal/stem cells (MSCs) have revealed a reparatory capability, preventing the progression of BPD in animal models. Administering MSC-conditioned media containing extracellular vesicles (EVs) have also demonstrated a preventive action, without the potential risks associated with unwanted engraftment or the adverse effects of administering cells. In this paper, we explore these emerging treatments and take a look at the revolutionary changes in BPD and neonatology on the horizon. Full article

Preterm infants frequently suffer from respiratory distress syndrome (RDS), possibly due to lower expression of epithelial Na⁺ channels (ENaC). RDS incidence is sex-specific, affecting males almost twice as often. Despite the use of antenatal glucocorticoids (GCs), the sex difference persists. It is still controversial whether both sexes benefit equally from GCs. We previously showed that Na⁺ transport is higher in female compared with male fetal distal lung epithelial (FDLE) cells. Since GCs increase Na⁺ transport, we hypothesized that their stimulating effect might be sex-specific. We analyzed FDLE cells with Ussing chambers and RT-qPCR in the presence or absence of fetal serum. In serum-free medium, GCs increased the ENaC activity and mRNA expression, independent of sex. In contrast, GCs did not increase the Na⁺ transport in serum-supplemented media and abolished the otherwise observed sex difference. Inhibition of the GC receptor in the presence of serum did not equalize Na⁺ transport between male and female cells. The GC-induced surfactant protein mRNA expression was concentration and sex-specific. In conclusion, female and male FDLE cells exhibit no sex difference in response to GCs with regard to Na⁺ transport, and GR activity does not contribute to the higher Na⁺ transport in females. Full article

Glucocorticoid hormones (GCs) released from the fetal/maternal glands during late gestation are required for normal development of mammalian organs and tissues. Accordingly, synthetic glucocorticoids have proven to be invaluable in perinatal medicine where they are widely used to accelerate fetal lung maturation when there is risk of pre-term birth and to promote infant survival. However, clinical and pre-clinical studies have demonstrated that inappropriate exposure of the developing brain to elevated levels of GCs, either as a result of clinical over-use or after stress-induced activation of the fetal/maternal adrenal cortex, is linked with significant effects on brain structure, neurological function and behaviour in later life. In order to understand the underlying neural processes, particular interest has focused on the midbrain dopaminergic systems, which are critical regulators of normal adaptive behaviours, cognitive and sensorimotor functions. Specifically, using a rodent model of GC exposure in late gestation (approximating human brain development at late second/early third trimester), we demonstrated enduring effects on the shape and volume of the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) (origins of the mesocorticolimbic and nigrostriatal dopaminergic pathways) on the topographical organisation and size of the dopaminergic neuronal populations and astrocytes within these nuclei and on target innervation density and neurochemical markers of dopaminergic transmission (receptors, transporters, basal and amphetamine-stimulated dopamine release at striatal and prefrontal cortical sites) that impact on the adult brain. The effects of antenatal GC treatment (AGT) were both profound and sexually-dimorphic, not only in terms of quantitative change but also qualitatively, with several parameters affected in the opposite direction in males and females. Although such substantial neurobiological changes might presage marked behavioural effects, in utero GC exposure had only a modest or no effect, depending on sex, on a range of conditioned and unconditioned behaviours known to depend on midbrain dopaminergic transmission. Collectively, these findings suggest that apparent behavioural normality in certain tests, but not others, arises from AGT-induced adaptations or compensatory mechanisms within the midbrain dopaminergic systems, which preserve some, but not all functions. Furthermore, the capacities for molecular adaptations to early environmental challenge are different, even opponent, in males and females, which may account for their differential resilience or failure to perform adequately in behavioural tests. Behavioural “normality” is thus achieved by the midbrain dopaminergic network operating outside its normal limits (in a state of allostasis), rendering it at greater risk to malfunction when challenged in later life. Sex-specific neurobiological programming of midbrain dopaminergic systems may, therefore, have psychopathological relevance for the sex bias commonly found in brain disorders associated with these systems, and which have a neurodevelopmental component, including schizophrenia, ADHD (attention/deficit hyperactivity disorders), autism, depression and substance abuse. Full article