Table 1.

Experimental models and mechanisms of reduced nephron number

Experimental Model	Proposed Mechanism of Nephron Number Reduction	Reference
Maternal low-protein diet	↑apoptosis in metanephros and postnatal kidney	169–171
	Altered gene expression in developing kidney
	Altered gene methylation
	↓placental 11-βHSD2 expression
Maternal vitamin A restriction	↓branching of ureteric bud	172
	? maintenance of spatial orientation of vascular development
	↓c-ret expression
Maternal iron restriction	? reduced oxygen delivery	173
	? altered glucocorticoid responsiveness
	? altered micronutrient availability
Gestational glucocorticoid exposure	↑fetal glucocorticoid exposure	108,174–176
	? enhanced tissue maturation
	↑glucocorticoid receptor expression
	↑1α- and β-ATPase expression
	↓renal and adrenal 11-βHSD2 expression
Uterine artery ligation/embolization	↑proapoptotic gene expression	177,178
	↓antiapoptotic gene expression
	Altered gene methylation
	Altered renin-angiotensin gene expression
Maternal diabetes/hyperglycemia	↓IGF-11/mannose-6-phosphate receptor expression	64,179,180
	Altered IGF-11 activity/bioavailability
	Activation of NF-κB
Gestational drug exposure		181–184
gentamicin	↓branching morphogenesis
β lactams	↑mesenchymal apoptosis
cyclosporine	Arrest of nephron formation
ethanol	? via reduced vitamin A levels
COX2 inhibitors	Affects prostaglandins

11-βHSD2, 11β-hydroxysteroid dehydrogenase 2; COX, cyclooxygenase. Adapted from: Luyckx VA, Brenner BM: Nephron endowment. In: The Kidney, 8th Ed., edited by Brenner BM, Philadelphia, W.B. Saunders, 2008, pp 654–673.