Prenatal Glucocorticoids: Short-Term Benefits and Long-Term Risks

Manojlović‐Stojanoski, Milica; Nestorović, Nataša; Milošević, Verica

doi:10.5772/51106

Cited by 15 publications

(22 citation statements)

References 257 publications

(336 reference statements)

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Section: Hpa Axis Function During Developmentmentioning

confidence: 99%

“…Glucocorticoids promote fetal maturation, as they affect the developmental and maturational processes of a variety of tissues and organs, in order to enable functional adaptations requested for extrauterine survival. Under constantly changing environmental conditions, the survival of newborns depends on the maintenance of homeostasis, thermogenesis and a stable energy supply, in view of the transition from placental to enteral nutrition (12). To achieve this, glucocorticoids influence the timely differentiation of vital organ systems, including the central nervous system, gastrointestinal system, as well as other endocrine axes and tissue hormones sensitivity.…”

Section: Hpa Axis Function During Developmentmentioning

confidence: 99%

Section: Antenatal Treatment and Fetal Hpa Axis Functionmentioning

confidence: 99%

“…Glucocorticoids control the proliferative activity of cells at all the HPA axis levels, and influence the gene expression of receptors, enzymes, ion channels, as well as cytoarchitectural proteins. All these changes at the cellular and molecular level result in altered set points of the delicate hormonal feedback mechanisms that become evident during the life cycle, under basal or stress circumstances (12,29,30).The hippocampus has a central role in the negative-feedback regulation of HPA axis by glucocorticoids which interact with the abundantly expressed GR and mineralocorticoid receptors (MR). Application of synthetic glucocorticoids during pregnancy provokes a sex-specific influence according to hippocampal mRNA GR and MR levels in fetuses.…”

mentioning

confidence: 99%

“…To achieve this, glucocorticoids influence the timely differentiation of vital organ systems, including the central nervous system, gastrointestinal system, as well as other endocrine axes and tissue hormones sensitivity. Fetal lung maturation and surfactant production, enhancement of gluconeogenic enzyme activities in the liver and glycogen deposition, as well as adaptive thermogenesis in brown adipose tissue are also controlled by glucocorticoid action (12)(13)(14).Like in adults, where stress implicates an HPA axis response, adverse intrauterine conditions in fetuses also provoke fetal HPA axis activation (15). For example, fetal hypoxemia leads to an increase in the fetal ACTH concentration with up-regulation of mRNAs of the ACTH receptor and steroid-synthesizing enzymes in the adrenals that result in selective increase of cortisol synthesis in fetal sheep (16).…”

mentioning

confidence: 99%

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Antenatal Treatment with Glucocorticoids and the Hypotalamic-Pituitary-Adrenal Axis

Manojlović‐Stojanoski¹,

Ristić²,

Singh³

et al. 2014

Journal of Medical Biochemistry

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SummaryFetal development is a critical period in the life cycle which is why the placenta provides a structural and physiological barrier that protects the fetus from the outer fluctuations and inner disturbances. A variety of influences from the environment, however, might induce fetal overexposure to glucocorticoids that target the fetal hypothalamic-pituitaryadrenal (HPA) axis and influence the fetal growth trajectory. Development of the HPA axis starts in the early stages of pregnancy, but the timing of HPA axis maturation and the glucocorticoid receptor (GR) expression in relation to birth is highly species-specific. The functional state of the fetal HPA axis plays a key role in the maturation of many organs necessary for intrauterine development and existence after birth. A functional HPA axis in near-term fetuses provides an adequate response to stress and also affects the timing of parturition. Due to their potent effect on the maturation of fetal tissues, synthetic glucocorticoids are used in human pregnancy at risk of preterm delivery. Dexamethasone and betamethasone, as the ones most commonly used, cross the placental enzymatic barrier (11b-hydroxysteroid dehydrogenase type 2 -11b-HSD2) and have 25-fold higher affinity to the GR than endogenous glucocorticoids, stimulating many aspects of fetal maturation. Despite the numerous positive effects, exposure to synthetic glucocorticoids during fetal development may result in intrauterine growth retardation and fetal programming of the HPA axis function which is associated with cardiovascular, metabolic and psychiatric disorders manifested later in life. Long-term consequences indicate the need for the implementation of new studies that will pro- Kratak sadr`ajFetalni razvoj predstavlja kriti~an period tokom `ivotnog ci klusa, zbog ~ega placenta obezbe|uje strukturnu i fiziolo{ku barijeru koja {titi fetus od spolja{njih kolebanja i unutra{njih poreme}aja. Brojni uticaji iz okru`enja mogu dovesti do izlaganja fetusa povi{enoj koncentraciji glukokor tikoida koji deluju na fetalnu hipotalamo-hipofiznoadrenalnu (HPA) oso vinu i uti~u na rast. Razvoj HPA osovine po~inje veoma rano tokom gestacije, ali vreme njenog sazrevanja i ekspresije glukokortikoidnog receptora (GR) u odnosu na ro|enje je specifi~no za svaku vrstu. Fetalna HPA osovina ima klju~nu ulogu u sazrevanju brojnih organa tokom intrauterinog raz voja neophodnih za pre`ivljavanje nakon ro|enja, obezbe |uje adekvatan odgovor fetusa na stres, a uti~e i na vreme poro|aja. Usled sna`nog uticaja na sazrevanje fetalnih tkiva, sintetski glukokortikoidi se upotrebljavaju tokom rizi~nih trudno}a kod kojih postoji opasnost od prevremenog poro|aja. Deksametazon i betametazon, kao naj~e{}e kori{}eni lekovi u antenatalnoj terapiji, prolaze enzimsku placentalnu barijeru (11b-hidroksisteroid dehidrogenaza tip 2 -11b-HSD2) i imaju 25 puta ve}i afinitet vezivanja za GR u odnosu na endogene gluko kortikoide, stimuli{u}i mnoge procese sazrevanja fetusa. Uprkos brojnim pozitivnim efektima, izlaganje sintetskim glukokorti...

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Section: Hpa Axis Function During Developmentmentioning

confidence: 99%

Section: Hpa Axis Function During Developmentmentioning

confidence: 99%

Section: Antenatal Treatment and Fetal Hpa Axis Functionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Antenatal Treatment with Glucocorticoids and the Hypotalamic-Pituitary-Adrenal Axis

Manojlović‐Stojanoski¹,

Ristić²,

Singh³

et al. 2014

Journal of Medical Biochemistry

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Reproductive outcomes of neonatal exposure to betamethasone in male and female rats

Figueiredo

Barros

Borges

et al. 2022

J of Applied Toxicology

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Betamethasone (BM) is the drug of choice for antenatal corticosteroid therapy for women at risk of preterm delivery because it induces fetal lung maturation and enhances survival after birth. However, our group reported evidence of fetal programming and impaired reproductive development and function in rats exposed during the critical window of genital system development. Therefore, we aimed to investigate the effects of BM on the sexual development of rats in the period that corresponds to antenatal corticosteroid therapy in humans. Male and female rats were exposed subcutaneously to BM at 0.1 μg/g of pups' body weight or to a NaCl 0.9% solution (control) on postnatal days 1–3. It was observed that neonatal exposure to BM decreased body weight and weight gain in male and female rats during treatment. The estrous cycle was deregulated and LH level was decreased in female rats. In male rats, the sperm concentration in the caput–corpus of the epididymis was decreased, whereas the sperm transit time and sperm concentration in the cauda of the epididymis were increased. Our results demonstrated that neonatal exposure to BM impaired body growth of male and female rats, deregulated the estrous cycle of female rats, and altered sperm quality of male rats. Therefore, BM exposure from postnatal days 1 to 3 corroborated results previously observed after prenatal exposure to this drug. Despite the recognized importance of human antenatal corticosteroid therapy, the findings of this study should encourage further studies in order to minimize possible adverse postnatal effects.

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Exposure to dexamethasone reduces pituitary volume and gonadotropic cell number in rat fetuses

Ristić

Nestorović

Manojlović‐Stojanoski

et al. 2014

Acta Histochemica

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Prenatal Glucocorticoids: Short-Term Benefits and Long-Term Risks

Cited by 15 publications

References 257 publications

Antenatal Treatment with Glucocorticoids and the Hypotalamic-Pituitary-Adrenal Axis

Antenatal Treatment with Glucocorticoids and the Hypotalamic-Pituitary-Adrenal Axis

Reproductive outcomes of neonatal exposure to betamethasone in male and female rats

Exposure to dexamethasone reduces pituitary volume and gonadotropic cell number in rat fetuses

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