Placental Restriction Alters the Functional Development of the Pituitary-Adrenal Axis in the Sheep Fetus during Late Gestation

Phillips, Ian D.; Simonetta, Giuseppe; Owens, Julie A.; Robinson, J. S.; Clarke, I. J.; McMillen, I. C.

doi:10.1203/00006450-199612000-00014

Cited by 120 publications

(104 citation statements)

References 19 publications

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“…Acute hypoxia has been reported to stimulate the circulating RAS, although nothing is known about its effects on the fetal intrarenal RAS (Wood, 1995). Placental restriction also causes fetal hypoglycaemia (Phillips et al 1997), which is also associated with low levels of insulin-like growth factor-1 (IGF-1) levels (Bassett et al 1990;Owens et al 1994;Kind et al 1995). We have recently shown that exogenous infusions of IGF-1 stimulate the activity of the circulating RAS (Marsh et al 1998) and activate renin gene expression and synthesis (A.…”

Section: Discussionmentioning

confidence: 99%

Effects of placental insufficiency on the ovine fetal renin-angiotensin system

Zhang¹,

Lumbers²,

Simonetta³

et al. 2000

Exp. Physiol.

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Section: Discussionmentioning

confidence: 99%

Effects of placental insufficiency on the ovine fetal renin-angiotensin system

Zhang¹,

Lumbers²,

Simonetta³

et al. 2000

Exp. Physiol.

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“…The effect on HPA axis development of direct experimental disruption of the intrauterine environment has also been studied. In the sheep, surgical restriction of placental size produces a decrease in the level of the ACTH precursor, proopiomelanocortin (POMC) mRNA, present in the fetal pituitary (Phillips et al 1996). The effect of maternal undernutrition on the intrauterine environment and consequently the fetal HPA axis is unknown.…”

Section: Introductionmentioning

confidence: 99%

“…An adverse intrauterine environment affects development of fetal tissues and organs (Crowe et al 1995, Phillips et al 1996. Epidemiological evidence suggests that adult diseases such as coronary heart disease, hypertension and non-insulin-dependent diabetes may originate in utero (see Barker 1998).…”

Section: Introductionmentioning

confidence: 99%

Effect of maternal nutrient restriction in early gestation on development of the hypothalamic-pituitary-adrenal axis in fetal sheep at 0.8-0.9 of gestation

Hawkins

Steyn²,

Mcgarrigle³

et al. 1999

Journal of Endocrinology

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The fetal hypothalamic-pituitary-adrenal (HPA) axis has numerous key roles in development. Epidemiological data have linked adverse prenatal nutrition with altered organ development and increased incidence of disease in adult life. We studied HPA axis development in resting and stimulated states in late gestation fetal sheep, following 15% reduction in maternal nutritional intake over the first 70 days of gestation (dGA). Fetuses from control (C) and nutrient-restricted (R) ewes were chronically catheterised and response profiles for ACTH and cortisol were determined at 113-116 and 125-127 dGA after administration of corticotrophin releasing hormone (CRH) and arginine vasopressin (AVP). At 126-128 dGA cortisol profiles were also determined following ACTH administration. Basal ACTH and cortisol concentrations were not different between C and R fetuses. In R fetuses, ACTH response to CRH+AVP was significantly smaller at 113-116 dGA (P<0·01), and cortisol responses were smaller at both 113-116 dGA (P<0·01) and 125-127 dGA (P<0·0001). Cortisol response to ACTH was also smaller in R fetuses (P<0·001). We conclude that, in late gestation fetal sheep, pituitary and adrenal responsiveness is reduced following modest maternal nutrient restriction in early gestation.

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“…7,8 It is also noteworthy that IUGR newborns appear to have elevated cortisol levels. [9][10][11] A key factor in determining glucocorticoid hormone action is the 'prereceptor' role played by two distinct isozymes of 11b-hydroxysteroid dehydrogenase (11b-HSD1 and 11b-HSD2 coded by HSD11B1 and HSD11B2, respectively), which interconvert hormonally active cortisol to inactive cortisone. 11b-HSD1 is expressed in the maternal decidua but low or absent in human fetal tissues including trophoblast, whereas 11b-HSD2 is widely distributed in human fetal tissues, including the placental trophoblast where it is expressed in particularly high abundance.…”

Section: Introductionmentioning

confidence: 99%

Site-specific methylation of placental HSD11B2 gene promoter is related to intrauterine growth restriction

et al. 2013

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Intrauterine growth restriction (IUGR) is associated with detrimental effects on neurodevelopmental progress in childhood and higher risk of degenerative diseases in adulthood. Placental 11b-hydroxysteroid dehydrogenase (HSD11B2) is a key gene involved in glucocorticoid metabolism, which in turn seems to be related to fetal growth impairment. As reduction of placental HSD11B2 gene expression has been associated with reduced human fetal growth, and methylation of HSD11B2 gene promoter has been shown to have an important role in HSD11B2 gene repression, we seek to investigate the relationship between IUGR and HSD11B2 gene promoter methylation in human placentas. We found that methylation levels of all studied CpG sites were significantly higher in IUGR newborns than those in controls. Further, methylation levels of the first and the third CpG sites were inversely associated with measures of fetal growth (birth weight and ponderal index). In addition, consistent with the above negative correlation, methylation levels of the first and the third CpG sites were inversely associated with HSD11B2 gene expression. These results together show a link between the site-specific methylation of placental HSD11B2 promoter and the development of IUGR.

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Placental Restriction Alters the Functional Development of the Pituitary-Adrenal Axis in the Sheep Fetus during Late Gestation

Cited by 120 publications

References 19 publications

Effects of placental insufficiency on the ovine fetal renin-angiotensin system

Effects of placental insufficiency on the ovine fetal renin-angiotensin system

Effect of maternal nutrient restriction in early gestation on development of the hypothalamic-pituitary-adrenal axis in fetal sheep at 0.8-0.9 of gestation

Site-specific methylation of placental HSD11B2 gene promoter is related to intrauterine growth restriction

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