Fetal exposure to excess glucocorticoid is one of the critical factors for the fetal origins of adult diseases. However, the mechanism of the local regulation of glucocorticoid activity in the human placenta of pregnancies complicated with gestational diabetes mellitus (GDM) has not been fully understood. We investigated placental 11β-hydroxysteroid dehydrogenases (11β-HSDs) expression, and analyzed their relationship with cortisol levels in maternal and umbilical vein. Pregnant women with GDM after diet intervention (n=23) or normal glucose tolerance (NGT, n=22) were studied at the community-based hospital. We collected maternal and umbilical venous cord blood and placental tissues from both groups. Explanted placentas from NGT were cultured with palmitic acid, dexamethasone, insulin or their mixture for 24-h. We examined plasma cortisol, cortisone to cortisol ratio, insulin, the homeostasis model assessment of insulin resistance index (HOMA-IR) and the insulin secretion index. Quantitative real-time PCR, Western blot and immunohistochemical assay were applied for the measurement of 11β-HSD1 and 11β-HSD2 mRNA and protein. GDM had higher maternal cortisol levels, HOMA-IR, insulin secretion index and higher cortisone to cortisol ratio in umbilical vein. No significant change in cortisol levels in umbilical vein and newborn weight was found. GDM placental 11β-HSD1 levels decreased while 11β-HSD2 increased. Treatment of placenta explants from NGT with palmitic acid, dexamethasone, insulin or their combination resulted in a significant drop of 11β-HSD1 and increase in 11β-HSD2. Differential expression of 11β-HSDs in diet-treated GDM placenta provides a protective mechanism for the fetus throughout the adverse environment of pregnancy by limiting excessive exposure of the fetus to glucocorticoid.
[Show abstract][Hide abstract] ABSTRACT: The beneficial effects of antenatal steroids in women at risk of preterm birth are evident. A dose of 24 mg appears sufficient, but there are insufficient data to recommend betamethasone or dexamethasone, a single steroid dose, the optimal interval between doses and repeated courses, the gestational age at which treatment is beneficial and the long-term effects of steroid treatment. This review addresses these aspects of antenatal steroid treatment.
Although the 12-h and 24-h dosing intervals are equivalent with respect to prevention of respiratory distress syndrome, the former enables the completion of treatment in 50% more neonates delivered prematurely. Reducing the single steroid dose in patients at risk for premature birth reduces the associated maternal side effects. An inverse relationship has been demonstrated between the number of corticosteroid courses and foetal growth. The reduced size of exposed foetuses has been attributed to birth at earlier gestational ages and decreased foetal growth. Evidence suggests that antenatal exposure to synthetic glucocorticoids in term-born children has long-lasting effects, which may have important implications in the recommendation of steroids before elective caesarean at term.
The short-term and long-term effects of the dosage regimen on the pregnant mother and foetus remain unclear.
Current opinion in obstetrics & gynecology 01/2014; 26(2). DOI:10.1097/GCO.0000000000000047 · 2.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In normal pregnancy cortisol increases, however further pathologic increases in cortisol are associated with maternal and fetal morbidities. These experiments were designed to test the hypothesis that increased maternal cortisol would increase maternal glucose concentrations, suppress fetal growth, and impair neonatal glucose homeostasis. Ewes were infused with cortisol (1 mg/kg/d) from day 115 of gestation to term; maternal glucose, insulin, oPL, estrone, progesterone, non-esterified free fatty acids (NEFA), β-hydroxybutyrate (BHB), and electrolytes were measured. Infusion of cortisol increased maternal glucose concentration, and slowed the glucose disappearance after injection of glucose; maternal infusion of cortisol also increased the incidence of fetal death at or near parturition. The design of the study was altered to terminate the study prior to delivery and post-hoc analysis of the data was performed in order to test the hypothesis that maternal metabolic factors predict the fetal outcome. In cortisol-infused ewes that had stillborn lambs, plasma insulin was increased relative to control ewes or cortisol-infused ewes with live lambs. Maternal cortisol infusion did not alter maternal food intake, or plasma NEFA, BHB, estrone, progesterone or placental lactogen concentrations, or alter fetal body weight, ponderal index, or fetal organ weights. Our study suggests that the adverse effect of elevated maternal cortisol on pregnancy outcome may be related to the effects of cortisol on maternal glucose homeostasis, and suggest that chronic maternal stress or adrenal hypersecretion of cortisol may create fetal pathophysiology paralleling that of maternal gestational diabetes.
[Show abstract][Hide abstract] ABSTRACT: The prevalence of obesity among child-bearing women has increased significantly. Adverse consequences of maternal obesity on the descendants have been well accepted, but few studies have examined the underlying mechanisms. We investigated whether neonatal overfeeding in female mice alters metabolic phenotypes in their offspring and whether hypothalamic leptin signaling is involved. Neonatal overfeeding was induced by reducing the litter size to 3pups/litter, in contrast with normal litter size of 10pups/litter. Normal and neonatally overfed female mice were bred with normal male mice, and offspring of overfeeding mothers (OOM) and control mothers (OCM) were generated. We examined body weight, daily food intake, leptin responsiveness, and the number of positive neurons for phospho-signal transducer and activator of transcription-3 (pSTAT3) along with neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus (ARH) and NPY in the nucleus tractus solitarius (NTS) of the brain stem. The body weight and daily food intake of OOM were significantly higher than those of OCM. Leptin significantly reduced food intake and increased the number of pSTAT3 positive neurons in the ARH of OCM mice, whereas no significant changes in food intake and pSTAT3 neurons were found in the leptin-treated OOM mice. The number of NPY neurons in the ARH and NTS of the OOM mice was significantly higher than that of the OCM mice. Our studies indicated that the obese phenotype from mothers can be passed onto the subsequent generation, which is possibly associated with hypothalamic leptin resistance. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Journal of Neuroendocrinology 04/2015; 27(7). DOI:10.1111/jne.12281 · 3.14 Impact Factor
Note: This list is based on the publications in our database and might not be exhaustive.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.