PHYS30001 Lecture Notes - Lecture 29: Kidney Development, Apoptosis, Maternal Insult
Document Summary
Increased arterial pressure due to increased backflow of blood. Hypertrophy: expansion to take on greater filtered load. Glomerulosclerosis leads to further reduction in nephron number. Sheep model: prenatal glucocorticoid exposure dysregulates nephron number. Synthetic stress hormone (dexamethasone) given to the mother for 2 days, then measure offspring bp - as they got older, bp was higher and got worse. Nephron number at 7 years of age following prenatal dex. Babies had similar birth weight/kidney weight, but nearly half the number of nephrons. Altered ras activity can regulate apoptosis and branching, At birth, renal adaptations occur, some good some bad. But: not all individuals with low nephron number get hypertension. Glucocorticoid given from e12. 5-14. 5 (same model as microarray data where 1500 genes were found to be altered) Glucocorticoid dysregulates numerous factors involved in branching morphogenesis (bpm4, at1, at2) as early as e14. 5. Both males/females have reduced nephron number (similar mechanism by which nephrogenesis is impaired) but females don"t get high bp.
