Antenatal Dexamethasone: Effect on Ovine Placental 11β-Hydroxysteroid Dehydrogenase Type 2 Expression and Fetal Growth

Kerzner, Leslie S; Stonestreet, Barbara S.; Wu, Ke-Ying; Sadowska, Grazyna B.; Malee, Maureen P.

doi:10.1203/00006450-200211000-00016

Cited by 22 publications

(15 citation statements)

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“…One study found that the male fetus was more vulnerable to the effects of maternal prenatal stress [29]. Another study found reduced expression and activity of placental 11β-HSD2 (a placental enzyme that protects the fetus from harmful effects of stress) in male fetuses compared to their female counterparts [30, 32]. Finally, many epidemiological studies have shown that fetal morbidity/mortality, neurodevelopmental alterations, and pregnancy complications are more associated with male fetuses than females [10, 33].…”

Section: Discussionmentioning

confidence: 99%

Maternal Intimate Partner Violence: Relationships with Language and Neurological Development of Infants and Toddlers

Udo¹,

Sharps

Bronner

et al. 2016

Matern Child Health J

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Objectives This longitudinal study examined the influence of Intimate Partner Violence (IPV) experience of pregnant women participating in the Domestic Violence Enhanced Home Visitation Program (DOVE) on the language and neurological and development of infants and toddlers. Methods A total of 210 infants and toddlers born to women reporting low, moderate, and high levels of IPV were included in the analysis. Logistic regression analysis was used to determine the bivariate association between maternal IPV and risk of language and neurological delay of infants and toddlers and between covariates and language and neurological delay. Generalized Estimating Equation models with logit link was used to predict the risk for neurological and language delay of infants and toddlers as a result of maternal IPV. Results Infants and toddlers born to women exposed to moderate levels of IPV had increased odds of language delay compared to infants and toddlers of women who experienced low levels of violence (OR=5.31, 95% CI=2.94, 9.50, p<0.001). Infants and toddlers born to women who experienced moderate and high levels of IPV were at higher risk of neurological delay respectively, compared to infants and toddlers of women who experienced low levels of IPV (OR=5.42, 95% CI=2.99, 9.82, p<0.001 & OR=2.57, 95% CI=1.11, 5.61, p=0.026). Conclusions Maternal IPV is associated with increased risk of language and neurological delay of infants and toddlers. These findings have implications for health care for women and infants exposed to IPV. Clinicians including pediatricians working with pregnant women should screen for IPV throughout pregnancy to identify women and children at risk. Interventions to reduce maternal IPV and early intervention services for infants and toddlers exposed to IPV are necessary for optimal maternal and child health.

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Section: Discussionmentioning

confidence: 99%

Maternal Intimate Partner Violence: Relationships with Language and Neurological Development of Infants and Toddlers

Udo¹,

Sharps

Bronner

et al. 2016

Matern Child Health J

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“…Clarke et al showed that the decrease in 11β-HSD2 activity in ovine placentomes was associated with the rise in fetal plasma cortisol concentrations towards term, suggesting that cortisol may suppress 11β-HSD2 activity in late gestation [24]. In ewes, maternal treatment with dexamethasone also reduces placental 11β-HSD2 expression [25]. In contrast, expression of 11β-HSD1 in human chorionic trophoblasts was increased by incubation with 0.1–1 μM cortisol (REF: Li et al 2006 Endo.)…”

Section: Discussionmentioning

confidence: 99%

Physiological changes in maternal cortisol do not alter expression of growth-related genes in the ovine placenta

et al. 2010

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Objectives The aim of this study was to investigate the effect of cortisol on growth-related genes in the ovine placenta. Study design Ewes carrying singleton pregnancies were operated on between 112 and 116 days of gestation (115 ± 0.4, term=147 days) and randomly assigned into three groups: six control animals, five ewes that were administered cortisol by continuous intravenous infusion (1 mg/kg/day) (high cortisol), and five ewes that were adrenalectomized and replaced with 0.5–0.6 mg cortisol/kg/day and 3 μg aldosterone/kg/day to produce cortisol concentrations equivalent to pre-pregnancy values (low cortisol). At necropsy (130 ± 0.2 days of gestation), placental tissue was frozen and stored at −80°C for mRNA analysis. Main outcome measures To assess potential molecular mechanisms by which cortisol alters placental structure and function and fetal growth. Results Cortisol levels did not significantly affect 11β-hydroxysteroid dehydrogenase 1 and 2 enzymes, glucocorticoid receptor, mineralocorticoid receptor and angiotensin II receptor, type 1 (AT1R) expression levels. Gene expression levels of AT2R were increased in the high cortisol group for type B placentomes. There was little effect of cortisol on the insulin-like growth factor (IGF) axis. There was significantly more IGF-I mRNA in B versus A type and more IGFBP-2 mRNA in B and C type versus A type placentomes regardless of treatment (p<0.05). Conclusions These data suggest that cortisol affects AT2R expression at high concentrations. Cortisol had little effect on the IGF axis in the placenta. However, the IGF axis might be involved in remodeling the fetal zone of placentomes during normal development.

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“…Another limitation of our study is that we did not perform functional outcomes for the connexins measured in our study. As described in the methods, fetal brain samples in the current study were derived from animals enrolled in our previous studies (Hai et al, 2002, Kerzner et al, 2002, Stonestreet et al, 2004, Sadowska et al, 2006, Sadowska et al, 2010) and, consequently, represented frozen samples.…”

Section: Discussionmentioning

confidence: 99%

“…The samples of fetal brain in this study were obtained from animals enrolled in our previous studies (Hai et al, 2002, Kerzner et al, 2002, Stonestreet et al, 2004, Sadowska et al, 2006, Sadowska et al, 2010). The surgical and experimental procedures have been previously reported (Stonestreet et al, 1996, Sadowska et al, 2006).…”

Section: Methodsmentioning

confidence: 99%

“…The pregnant ewes assigned to the single course groups were given four intramuscular injections of 6 mg of dexamethasone (Fujsawa USA, Deerfield, IL, concentration=4 mg/ml) or placebo (0.9% NaCl, 1.5 ml) over 48 hours every 12 hours. The pregnant ewes assigned to the multiple course groups were given the identical treatment once a week for five successive weeks beginning at 76–78 days of gestation as we previously described (Kerzner et al, 2002, Sadowska et al, 2006). After the pregnant sheep were given the fourth course of glucocorticoids, the fetuses and ewes were then catheterized at 99–101 days of gestation, so that the timing of surgery in the fetuses and ewes exposed to the multiple courses would be the identical to those that were exposed to the single courses.…”

Section: Methodsmentioning

confidence: 99%

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Maternal treatment with glucocorticoids modulates gap junction protein expression in the ovine fetal brain

Sadowska

Stonestreet

2014

Neuroscience

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Gap junctions facilitate intercellular communication and are important in brain development. Connexins (Cx) comprise a transmembrane protein family that forms gap junctions. Cx-32 is expressed in oligodendrocytes and neurons, Cx-36 in neurons, and Cx-43 in astrocytes. Although single antenatal steroid courses are recommended for fetal lung maturation, multiple courses can be given to women at recurrent risk for premature delivery. We examined the effects of single and multiple glucocorticoid courses on Cx-32, Cx-36, and Cx-43 protein expression in fetal cerebral cortex, cerebellum, and spinal cord, and differences in connexin expression among brain regions under basal conditions. In the single course groups, the ewes received dexamethasone (6 mg) or placebo as four intramuscular injections every 12 h over 48 h. In the multiple course groups, the ewes received the same treatment, once a week for five weeks starting at 76–78 days of gestation. Connexins were measured by Western immunoblot on brain samples from 105–108 day gestation fetuses. A single dexamethasone course was associated with increases (P<0.05) in cerebral cortical and spinal cord Cx-36 and Cx-43 and multiple courses with increases in cerebellar and spinal cord Cx-36, and cerebral cortical and cerebellar Cx-43. Cx-32 did not change. Cx-32 was higher in cerebellum than cerebral cortex and spinal cord, Cx-36 higher in spinal cord than cerebellum, and Cx-43 higher in cerebellum and spinal cord than cerebral cortex during basal conditions. In conclusion, maternal glucocorticoid therapy increases specific connexins, responses to different maternal courses vary among connexins and brain regions, and connexin expression differs among brain regions under basal conditions. Maternal treatment with glucocorticoids differentially modulates connexins in the fetal brain.

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Antenatal Dexamethasone: Effect on Ovine Placental 11β-Hydroxysteroid Dehydrogenase Type 2 Expression and Fetal Growth

Cited by 22 publications

References 55 publications

Maternal Intimate Partner Violence: Relationships with Language and Neurological Development of Infants and Toddlers

Maternal Intimate Partner Violence: Relationships with Language and Neurological Development of Infants and Toddlers

Physiological changes in maternal cortisol do not alter expression of growth-related genes in the ovine placenta

Maternal treatment with glucocorticoids modulates gap junction protein expression in the ovine fetal brain

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