Reduced Placental 11 -Hydroxysteroid Dehydrogenase Type 2 mRNA Levels in Human Pregnancies Complicated by Intrauterine Growth Restriction: An Analysis of Possible Mechanisms

2001 ◽  
Vol 86 (10) ◽  
pp. 4979-4983 ◽  
Author(s):  
C. L. McTernan
Keyword(s):  
Intrauterine Growth Restriction ◽  
Hydroxysteroid Dehydrogenase ◽  
Growth Restriction ◽  
Mrna Levels ◽  
Intrauterine Growth

scholarly journals Reduced Placental 11β-Hydroxysteroid Dehydrogenase Type 2 mRNA Levels in Human Pregnancies Complicated by Intrauterine Growth Restriction: An Analysis of Possible Mechanisms

2001 ◽  
Vol 86 (10) ◽  
pp. 4979-4983 ◽  
Author(s):  
C. L. McTernan ◽  
N. Draper ◽  
H. Nicholson ◽  
S. M. Chalder ◽  
P. Driver ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Intrauterine Growth Restriction ◽  
Subsequent Development ◽  
Hydroxysteroid Dehydrogenase ◽  
Underlying Mechanism ◽  
Growth Restriction ◽  
Mrna Levels ◽  
Intrauterine Growth ◽  
Apparent Mineralocorticoid Excess

11β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2) inactivates cortisol to cortisone. In the placenta 11β-HSD2 activity is thought to protect the fetus from the deleterious effects of maternal glucocorticoids. Patients with apparent mineralocorticoid excess owing to mutations in the 11β-HSD2 gene invariably have reduced birth weight, and we have recently shown reduced placental 11β-HSD2 activity in pregnancies complicated by intrauterine growth restriction. This is reflected in the literature by evidence of hypercortisolemia in the fetal circulation of small babies. In this study we have determined the levels of placental 11β-HSD2 mRNA expression across normal gestation (n = 86 placentae) and in pregnancies complicated by intrauterine growth restriction (n = 19) and evaluated the underlying mechanism for any aberrant 11β-HSD2 mRNA expression in intrauterine growth restriction. 11β-HSD2 mRNA expression increased more than 50-fold across gestation, peaking at term. Placental 11β-HSD2 mRNA levels were significantly decreased in intrauterine growth restriction pregnancies when compared with gestationally matched, appropriately grown placentae [e.g. at termΔ Ct (11β-hydroxysteroid dehydrogenase type 2/18S) 12.8 ± 0.8 (mean ± se) vs. 10.2 ± 0.2, respectively, P < 0.001]. These differences were not attributable to changes in trophoblast mass in intrauterine growth restriction placentae, as assessed by parallel analyses of cytokeratin-8 mRNA expression. No mutations were found in the 11β-HSD2 gene in the intrauterine growth restriction cohort, and imprinting analysis revealed that the 11β-HSD2 gene was not imprinted. Although the underlying cause is unknown, 11β-HSD2 gene expression is reduced in intrauterine growth restriction pregnancies. These data highlight the important role of 11β-HSD2 in regulating fetal growth, a known factor in determining fetal morbidity but also the subsequent development of cardiovascular disease in adulthood.

scholarly journals Changes in 11 -hydroxysteroid dehydrogenase type 2 expression in a low-protein rat model of intrauterine growth restriction

2010 ◽  
Vol 25 (10) ◽  
pp. 3195-3203 ◽  
Author(s):  
I. Ostreicher ◽  
J. R. Almeida ◽  
V. Campean ◽  
M. Rauh ◽  
C. Plank ◽  
...  
Keyword(s):  
Rat Model ◽  
Intrauterine Growth Restriction ◽  
Hydroxysteroid Dehydrogenase ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
Low Protein

scholarly journals Alteration in 11 Beta-Hydroxysteroid Dehydrogenase Type-2 (HSD11B2) Gene as A Potential Candidate Parameter for Early Detection of Intrauterine Growth Restriction (IUGR) Events

2021 ◽  
Vol 5 (3) ◽  
pp. 98
Author(s):  
Louis Fabio Jonathan Jusni ◽  
Patricia Patricia ◽  
Brigitte Leonie Rosadi
Keyword(s):  
Early Detection ◽  
Doppler Ultrasound ◽  
Intrauterine Growth Restriction ◽  
Prenatal Testing ◽  
Hydroxysteroid Dehydrogenase ◽  
Growth Restriction ◽  
Diagnostic Parameter ◽  
Intrauterine Growth ◽  
Non Invasive

Intrauterine Growth Restriction (IUGR) incidence in Indonesia ranks in the top 10 of the highest in Asia. It is the main perinatal death cause. IUGR also impairs fetal neurodevelopment, which can affect the development of children until later ages. Lack of 11β-hydroxysteroid dehydrogenase type-2 (11β-HSD2) enzyme is influenced by changes in the coding gene, HSD11B2, one of IUGR's causes. The main diagnostic method of IUGR at this time is by using Doppler ultrasound. However, Doppler ultrasound has several limitations as many cases are not detected. Its clinical predictive value in various women is poor, as Doppler ultrasound is not recommended for use in the first trimester, detection of abnormalities in the second trimester seems to be too late for helpful interventions. The study aim is to present an overview concerning HSD11B2 gene alteration in an non-invasive prenatal testing (NIPT) as a possible diagnostic parameter for early detection in IUGR infants. This literature review is based on selected articles and studies taken from the Pubmed, Proquest, and EBSCO databases. A total of 4 studies reported the tendency for DNA methylation and decreased expression of the HSD11B2 gene in IUGR cases. Changes in the HSD11B2 gene have the potential to become a diagnostic parameter in the early detection of infants with IUGR. Further study and investigation of this possibility are needed.Keywords: intrauterine growth restriction, HSD11B2, early detection, diagnostic, non-invasive prenatal testing

scholarly journals 11Beta-hydroxysteroid dehydrogenase type 2 in human pregnancy and reduced expression in intrauterine growth restriction

1998 ◽  
Vol 13 (4) ◽  
pp. 799-804 ◽  
Author(s):  
M. Shams ◽  
M. D. Kilby ◽  
D. A. Somerset ◽  
A. J. Howie ◽  
A. Gupta ◽  
...  
Keyword(s):  
Intrauterine Growth Restriction ◽  
Hydroxysteroid Dehydrogenase ◽  
Growth Restriction ◽  
Human Pregnancy ◽  
Intrauterine Growth

Differential regulation of igf1 and igf1r mRNA levels in the two hepatic lobes following intrauterine growth restriction and its treatment with intra-amniotic insulin-like growth factor-1 in ovine fetuses

2010 ◽  
Vol 22 (8) ◽  
pp. 1188 ◽  
Author(s):  
Revati A. Darp ◽  
Hendrina A. de Boo ◽  
Hui Hui Phua ◽  
Mark H. Oliver ◽  
José G. B. Derraik ◽  
...  
Keyword(s):  
Growth Factor ◽  
Intrauterine Growth Restriction ◽  
Venous Blood ◽  
Growth Restriction ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Hepatic Lobe ◽  
Intrauterine Growth ◽  
The Right ◽  
Gut Maturation

Intrauterine growth restriction (IUGR) has life-long health implications, yet there is no effective prenatal treatment. Daily intra-amniotic administration of insulin-like growth factor (IGF)-1 to IUGR fetal sheep improves fetal gut maturation but suppresses hepatic igf1 gene expression. Fetal hepatic blood supply is regulated, in part, by shunting of oxygen- and nutrient-rich umbilical venous blood through the ductus venosus, with the left hepatic lobe predominantly supplied by umbilical venous blood and the right hepatic lobe predominantly supplied by the portal circulation. We hypothesised that: (1) once-weekly intra-amniotic IGF-1 treatment of IUGR would be effective in promoting gut maturation; and (2) IUGR and its treatment with intra-amniotic IGF-1 would differentially affect igf1 and igf1r mRNA expression in the two hepatic lobes. IUGR fetuses received 360 µg IGF-1 or saline intra-amniotically once weekly from 110 until 131 days gestation. Treatment of IUGR fetuses with IGF-1 reversed impaired gut growth. In unembolised, untreated control fetuses, igf1 mRNA levels were 19% lower in the right hepatic lobe than in the left; in IUGR fetuses, igf1 and igf1r mRNA levels were sixfold higher in the right lobe. IGF-1 treatment reduced igf1 and igf1r mRNA levels in both lobes compared with IUGR fetuses. Thus, weekly intra-amniotic IGF-1 treatment, a clinically feasible approach, reverses the impaired gut development seen in IUGR. Furthermore, igf1 and igf1r mRNA levels are differentially expressed in the two hepatic lobes and relative expression in the two lobes is altered by both IUGR and intra-amniotic IGF-1 treatment.

Novel Polymorphisms in the Angiotensin II type 2 Receptor Gene: Common Haplotypes and Implications for Intrauterine Growth Restriction (IUGR)

2002 ◽  
Vol 103 (s47) ◽  
pp. 60P-61P
Author(s):  
Clare Tower ◽  
Sally Plummer ◽  
Pedro Alonso ◽  
Linda Morgan ◽  
Philip Baker ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Intrauterine Growth Restriction ◽  
Receptor Gene ◽  
Growth Restriction ◽  
Intrauterine Growth

scholarly journals Diethylstilbestrol inhibits human and rat 11β-hydroxysteroid dehydrogenase 2

2019 ◽  
Vol 8 (7) ◽  
pp. 1061-1069
Author(s):  
Yiyan Wang ◽  
Yaoyao Dong ◽  
Yinghui Fang ◽  
Yao Lv ◽  
Qiqi Zhu ◽  
...  
Keyword(s):  
Mode Of Action ◽  
Intrauterine Growth Restriction ◽  
Area Under The Curve ◽  
Hydroxysteroid Dehydrogenase ◽  
Competitive Inhibitor ◽  
Growth Restriction ◽  
Sprague Dawley ◽  
Intrauterine Growth ◽  
Cortisol Metabolism ◽  
Metabolizing Enzyme

Glucocorticoid hormone might cause intrauterine growth restriction. The glucocorticoid-metabolizing enzyme 11β-hydroxysteroid dehydrogenase 2 (HSD11B2) in the placenta eliminates excess levels of glucocorticoids during pregnancy. The aim of the current study was to define the effects of diethylstilbestrol (DES) on HSD11B2 activity in the mammalian placentas and identify its mode of action. Rat and human placental microsomal HSD11B2 were incubated with different concentrations of DES, and IC50 values were determined. The mode of action was analyzed by incubation of DES together with substrates, glucocorticoid and NAD+. DES suppressed rat and human HSD11B2 with IC50 values of 5.33 and 12.62 μM, respectively. DES was a competitive inhibitor of rat and human HSD11B2 when steroid substrates were added, while it was an uncompetitive inhibitor when cofactor NAD+ was exposed. Oral administration of DES (0.5 mg/kg) to the rat delayed the cortisol metabolism in adult female Sprague–Dawley rats, as indicated by the increases in cortisol’s elimination half-life, maximum concentration and area under the curve. In conclusion, DES is a potent HSD11B2 inhibitor, possibly contributing to the intrauterine growth restriction.

Abstract 130: Sphingosine-1-Phosphate Signaling Plays a Role in High Blood Pressure Programmed by Intrauterine Growth Restriction in Mouse

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Suttira Intapad
Keyword(s):  
Protein Expression ◽  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Acute Administration ◽  
Mrna Levels ◽  
Male Control ◽  
Intrauterine Growth ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor

Intrauterine growth restriction (IUGR) is a risk factor for hypertension and cardiovascular (CV) disease in later life, but the underlying mechanisms remain unclear. The bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P) is critically involved in CV development in the fetus, and plays a significant role in the regulation of CV health in adulthood. S1P receptor (S1PR) type 1, 2 and 3 are widely expressed in CV system which S1PR1 has a protective role against kidney injury, while S1PR3 is involved in controlling BP. Yet, the contribution of S1P on BP in IUGR is unknown. In the present studies, we tested the hypothesis that IUGR alters renal S1P receptors expression during- and post-nephrogenesis, which contributes to high BP in male IUGR mouse. C57bl/6J mice underwent sham or reduced uterine perfusion (RUP) at day 13 of gestation with delivery at full term. IUGR offspring (from RUP dam) had a lower birth weight than control (p<0.05). Kidneys were isolated from 2 day old male pups or adult 24 week old male control and IUGR. S1PR3 protein expression was increased in 2 day old IUGR kidneys (2.4 fold vs control, N=3, p< 0.01). At 24 weeks of age, S1PR3 mRNA levels were increased (1.2 fold vs control, N=4, p< 0.05) whereas S1PR3 protein levels were decreased (0.75 fold vs control, N=4, p< 0.05) in IUGR kidneys. mRNA and protein expression levels of S1PR1 and S1PR2 were not different between control and IUGR kidneys. Finally, we assessed the role of S1PRs agonist on BP of IUGR. Male IUGR offspring had a significantly higher BP compared to male control via carotid catheter in the conscious state (control: 112.1±2.1, IUGR: 125.0±3.7 mmHg; N=7, P <0.05). Acute administration of FTY720 (1 mg/kgBW i.p, Fingomod), a S1P receptor type 1, 3 agonist did not significantly alter BP in control (106.0 ± 5.7 mmHg) but significantly decreased BP in IUGR (105.7±2.3 mmHg, p< 0.05). A dose response to FTY720 (10 mg/kgBW) decreased BP in both control (94.0±2.0 mmHg, p< 0.05) and IUGR (99.3±2.3 mmHg, p< 0.05). Together our data suggest that IUGR programs an alteration of renal S1PR3 expression in both during- and post-nephrogenesis thereby contributing to an increase in sensitivity to S1PRs agonist. Thus, S1P signaling is a putative mechanism underlying the hypertension of IUGR offspring.

scholarly journals Oxidative Stress, Intrauterine Growth Restriction, and Developmental Programming of Type 2 Diabetes

Physiology ◽  
2018 ◽  
Vol 33 (5) ◽  
pp. 348-359 ◽  
Author(s):  
Cetewayo S. Rashid ◽  
Amita Bansal ◽  
Rebecca A. Simmons
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Intrauterine Growth Restriction ◽  
Metabolic Diseases ◽  
Growth Restriction ◽  
Mitochondria Dysfunction ◽  
Intrauterine Growth ◽  
And Oxidative Stress

Intrauterine growth restriction (IUGR) leads to reduced birth weight and the development of metabolic diseases such as Type 2 diabetes in adulthood. Mitochondria dysfunction and oxidative stress are commonly found in key tissues (pancreatic islets, liver, and skeletal muscle) of IUGR individuals. In this review, we explore the role of oxidative stress in IUGR-associated diabetes etiology.

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