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Prenatal dexamethasone causes oligonephronia, sodium retention, and higher blood pressure in the offspring
1Institute of Women's and Child's Health, Karolinska Institute, Stockholm, Sweden.
Insights
Maternal exposure to high glucocorticoid levels during pregnancy can impair fetal kidney development, leading to adult hypertension in offspring. This occurs even when kidney size normalizes, due to glomerular damage and sodium retention.
Area of Science:
- Nephrology
- Developmental Biology
- Endocrinology
Background:
- Low birth weight is linked to increased adult hypertension risk.
- Mechanisms underlying this link require further investigation.
Purpose of the Study:
- To investigate the impact of maternal glucocorticoid exposure on fetal renal development and adult hypertension.
- To explore the role of dexamethasone versus hydrocortisone in programming hypertension.
Main Methods:
- Induction of fetal growth retardation in rats using maternal dexamethasone treatment.
- Assessment of pup kidney development, glomerular number, and cell mitosis.
- Measurement of adult body weight, blood pressure, glomerular filtration rate (GFR), albuminuria, and sodium balance.
Main Results:
- Dexamethasone-exposed pups had lower birth weight, kidney weight, and fewer glomeruli.
- Adult offspring exposed to dexamethasone exhibited significantly higher blood pressure, lower GFR, and increased albuminuria.
- Maternal hydrocortisone treatment did not result in abnormal fetal development or adult hypertension.
Conclusions:
- High maternal glucocorticoid levels during gestation impair renal development, predisposing offspring to arterial hypertension.
- Glomerular damage and impaired sodium handling contribute to hypertension development, despite normalization of renal mass.
- Placental metabolism of glucocorticoids is crucial in preventing these adverse effects.
Abstract:
Recent reports have shown that low birth weight infants have a higher incidence of adult hypertension. These observations have stimulated a number of studies designed to evaluate the mechanisms of this phenomenon. In this study, fetal growth retardation was induced by treating pregnant rats with dexamethasone. After birth, pups whose mothers were treated with dexamethasone had a lower body and kidney weight and a lower number of glomeruli than control pups. Immunohistochemistry on treated kidneys demonstrated a marked reduction in the number of cells undergoing mitosis in the cortical nephrogenic zone. In the treated group, body and kidney weight normalized by 60 d of age, but blood pressure was significantly higher compared with controls (130+/-4 versus 107+/-1 mm Hg). In addition, GFR was significantly lower, albuminuria was higher, urinary sodium excretion rate and fractional sodium excretion were lower, and sodium tissue content was higher. In contrast, when pregnant rats were treated with a natural glucocorticoid (hydrocortisone) which is metabolized by the placenta, fetal development and adult blood pressure were normal. In conclusion, we found that high levels of maternal glucocorticoids impair renal development and lead to arterial hypertension in offspring. Even though renal mass eventually normalizes, glomerular damage as well as sodium retention occur and these factors may contribute to the development of hypertension.