The impact of prenatal glucocorticoid exposure on the ovine kidney

Research output: ThesisDoctoral Thesis

222 Downloads (Pure)

Abstract

[Truncated abstract] In obstetric practice, pregnant women at risk of pre-term delivery between 24 and 34 weeks of gestation are administered synthetic glucocorticoids (betamethasone or dexamethasone) to induce fetal organ maturation. During this gestational period, the fetal kidney is undergoing a phase of rapid organogenesis with an increase in renal growth and active nephrogenesis occurring. The studies comprising this thesis examine the effects of prenatal betamethasone exposure on the fetal and adult ovine kidney. The central hypothesis of these studies was that exposure of the fetal kidney to betamethasone in late gestation would change renal structure and induce long-term alterations in the expression of glucocorticoid-sensitive genes and proteins. In the fetal studies, pregnant Merino ewes bearing single fetuses received single or repeated-weekly intra-muscular (i.m.) injections of betamethasone (0.5 mg/kg body weight) or saline commencing on day 104 of gestation (term is 150 days). Kidneys were collected from fetuses at 109, 116, 121 and 146 days of gestation (d). Using gold standard unbiased stereological techniques, the physical disector/fractionator method, total glomerular (nephron) number and glomerular volume were determined in 146 d fetal kidneys exposed to repeated maternal saline or betamethasone administration. In the adult study, kidneys were collected from 3.5-year-old sheep that had been exposed to ... In this thesis I have demonstrated that renal growth restriction as a result of betamethasone exposure is associated with a reduction in fetal nephron endowment. Although betamethasone does not appear to consistently alter nephron number or glomerular size, it may indirectly affect total nephron endowment through effects on renal growth. I have also provided evidence which suggests that lategestation betamethasone exposure in sheep does not program permanent alterations in the renal expression of genes or proteins involved in glucocorticoid hormone action or components of the renin-angiotensin system. Therefore, exposure of the fetal kidney to betamethasone during nephrogenesis may alter renal structure if kidney growth is perturbed; however, there are no persistent alterations in the expression of glucocorticoid-sensitive genes. These findings are consistent with the preservation of normal basal blood pressure in the adult sheep I studied and with the limited results from human studies of late-gestation maternal glucocorticoid administration.
Original languageEnglish
QualificationDoctor of Philosophy
Publication statusUnpublished - 2006

Fingerprint

Glucocorticoids
Sheep
Betamethasone
Kidney
Nephrons
Pregnancy
Financial Management
Growth
Fetus
Multifetal Pregnancy Reduction
Mothers
Organogenesis
Renin-Angiotensin System
Dexamethasone
Obstetrics
Pregnant Women
Proteins
Body Weight
Hormones
Blood Pressure

Cite this

@phdthesis{98288167b486476582d15d5732192dd6,
title = "The impact of prenatal glucocorticoid exposure on the ovine kidney",
abstract = "[Truncated abstract] In obstetric practice, pregnant women at risk of pre-term delivery between 24 and 34 weeks of gestation are administered synthetic glucocorticoids (betamethasone or dexamethasone) to induce fetal organ maturation. During this gestational period, the fetal kidney is undergoing a phase of rapid organogenesis with an increase in renal growth and active nephrogenesis occurring. The studies comprising this thesis examine the effects of prenatal betamethasone exposure on the fetal and adult ovine kidney. The central hypothesis of these studies was that exposure of the fetal kidney to betamethasone in late gestation would change renal structure and induce long-term alterations in the expression of glucocorticoid-sensitive genes and proteins. In the fetal studies, pregnant Merino ewes bearing single fetuses received single or repeated-weekly intra-muscular (i.m.) injections of betamethasone (0.5 mg/kg body weight) or saline commencing on day 104 of gestation (term is 150 days). Kidneys were collected from fetuses at 109, 116, 121 and 146 days of gestation (d). Using gold standard unbiased stereological techniques, the physical disector/fractionator method, total glomerular (nephron) number and glomerular volume were determined in 146 d fetal kidneys exposed to repeated maternal saline or betamethasone administration. In the adult study, kidneys were collected from 3.5-year-old sheep that had been exposed to ... In this thesis I have demonstrated that renal growth restriction as a result of betamethasone exposure is associated with a reduction in fetal nephron endowment. Although betamethasone does not appear to consistently alter nephron number or glomerular size, it may indirectly affect total nephron endowment through effects on renal growth. I have also provided evidence which suggests that lategestation betamethasone exposure in sheep does not program permanent alterations in the renal expression of genes or proteins involved in glucocorticoid hormone action or components of the renin-angiotensin system. Therefore, exposure of the fetal kidney to betamethasone during nephrogenesis may alter renal structure if kidney growth is perturbed; however, there are no persistent alterations in the expression of glucocorticoid-sensitive genes. These findings are consistent with the preservation of normal basal blood pressure in the adult sheep I studied and with the limited results from human studies of late-gestation maternal glucocorticoid administration.",
keywords = "Fetal tissues, Sheep, Fetuses, Physiology, Kidneys, Abnormalities, Effect of drugs on, Glucocorticoids, Ovine kidney, Antenatal corticosteroids",
author = "Amanda Meyer",
year = "2006",
language = "English",

}

TY - THES

T1 - The impact of prenatal glucocorticoid exposure on the ovine kidney

AU - Meyer, Amanda

PY - 2006

Y1 - 2006

N2 - [Truncated abstract] In obstetric practice, pregnant women at risk of pre-term delivery between 24 and 34 weeks of gestation are administered synthetic glucocorticoids (betamethasone or dexamethasone) to induce fetal organ maturation. During this gestational period, the fetal kidney is undergoing a phase of rapid organogenesis with an increase in renal growth and active nephrogenesis occurring. The studies comprising this thesis examine the effects of prenatal betamethasone exposure on the fetal and adult ovine kidney. The central hypothesis of these studies was that exposure of the fetal kidney to betamethasone in late gestation would change renal structure and induce long-term alterations in the expression of glucocorticoid-sensitive genes and proteins. In the fetal studies, pregnant Merino ewes bearing single fetuses received single or repeated-weekly intra-muscular (i.m.) injections of betamethasone (0.5 mg/kg body weight) or saline commencing on day 104 of gestation (term is 150 days). Kidneys were collected from fetuses at 109, 116, 121 and 146 days of gestation (d). Using gold standard unbiased stereological techniques, the physical disector/fractionator method, total glomerular (nephron) number and glomerular volume were determined in 146 d fetal kidneys exposed to repeated maternal saline or betamethasone administration. In the adult study, kidneys were collected from 3.5-year-old sheep that had been exposed to ... In this thesis I have demonstrated that renal growth restriction as a result of betamethasone exposure is associated with a reduction in fetal nephron endowment. Although betamethasone does not appear to consistently alter nephron number or glomerular size, it may indirectly affect total nephron endowment through effects on renal growth. I have also provided evidence which suggests that lategestation betamethasone exposure in sheep does not program permanent alterations in the renal expression of genes or proteins involved in glucocorticoid hormone action or components of the renin-angiotensin system. Therefore, exposure of the fetal kidney to betamethasone during nephrogenesis may alter renal structure if kidney growth is perturbed; however, there are no persistent alterations in the expression of glucocorticoid-sensitive genes. These findings are consistent with the preservation of normal basal blood pressure in the adult sheep I studied and with the limited results from human studies of late-gestation maternal glucocorticoid administration.

AB - [Truncated abstract] In obstetric practice, pregnant women at risk of pre-term delivery between 24 and 34 weeks of gestation are administered synthetic glucocorticoids (betamethasone or dexamethasone) to induce fetal organ maturation. During this gestational period, the fetal kidney is undergoing a phase of rapid organogenesis with an increase in renal growth and active nephrogenesis occurring. The studies comprising this thesis examine the effects of prenatal betamethasone exposure on the fetal and adult ovine kidney. The central hypothesis of these studies was that exposure of the fetal kidney to betamethasone in late gestation would change renal structure and induce long-term alterations in the expression of glucocorticoid-sensitive genes and proteins. In the fetal studies, pregnant Merino ewes bearing single fetuses received single or repeated-weekly intra-muscular (i.m.) injections of betamethasone (0.5 mg/kg body weight) or saline commencing on day 104 of gestation (term is 150 days). Kidneys were collected from fetuses at 109, 116, 121 and 146 days of gestation (d). Using gold standard unbiased stereological techniques, the physical disector/fractionator method, total glomerular (nephron) number and glomerular volume were determined in 146 d fetal kidneys exposed to repeated maternal saline or betamethasone administration. In the adult study, kidneys were collected from 3.5-year-old sheep that had been exposed to ... In this thesis I have demonstrated that renal growth restriction as a result of betamethasone exposure is associated with a reduction in fetal nephron endowment. Although betamethasone does not appear to consistently alter nephron number or glomerular size, it may indirectly affect total nephron endowment through effects on renal growth. I have also provided evidence which suggests that lategestation betamethasone exposure in sheep does not program permanent alterations in the renal expression of genes or proteins involved in glucocorticoid hormone action or components of the renin-angiotensin system. Therefore, exposure of the fetal kidney to betamethasone during nephrogenesis may alter renal structure if kidney growth is perturbed; however, there are no persistent alterations in the expression of glucocorticoid-sensitive genes. These findings are consistent with the preservation of normal basal blood pressure in the adult sheep I studied and with the limited results from human studies of late-gestation maternal glucocorticoid administration.

KW - Fetal tissues

KW - Sheep

KW - Fetuses

KW - Physiology

KW - Kidneys

KW - Abnormalities

KW - Effect of drugs on

KW - Glucocorticoids

KW - Ovine kidney

KW - Antenatal corticosteroids

M3 - Doctoral Thesis

ER -