Maturational regression of glomeruli determines the nephron population in normal mice.
BACKGROUND
Regression is an important process in the normal development of many organs. In this study, we investigated whether glomerular regression occurs after normal glomerulogenesis and determined the time course for this process.


METHODS
Glomerular number was analyzed in normal mouse kidneys at postnatal day (P)7, P10, P14, P18, P21, P25, and P28 by the gold standard fractionator/dissector method, which involves exhausting the kidney tissue. Vascular regression markers, angiopoietin 2 (ANGPT2), and thrombospondin 1 (THBS1), were examined by immunohistochemistry.


RESULTS
The maximum glomerular number was reached at P7 with 14,051 glomeruli per kidney (95% confidence interval: 12,084-16,018). This peak was followed by a progressive reduction, with a nadir of 11,060 (10,393-11,727) occurring at P18 (P < 0.05 as compared with P7). Thereafter, glomerular number remained constant. Complementary immunohistochemical examination of vascular regression markers showed peak expression of glomerular ANGPT2 and THBS1 at P14.


CONCLUSIONS
Our study reveals that the tissue- and time-saving Weibel-Gomez method commonly used to assess glomerular number is valid only after P18. The data indicate that regulation of glomerular number by regression occurs in normally maturing mouse kidneys. These findings suggest that the process of glomerular regression could be therapeutically targeted to prevent oligonephronia, which otherwise predisposes to chronic kidney disease.
Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, China.
Jianyong
J
Zhong
Daniel Scott
DS
Perrien
Hai-Chun
HC
Yang
Valentina
V
Kon
Agnes B
AB
Fogo
Iekuni
I
Ichikawa
Ji
J
Ma
D042702:Angiopoietin-2 / Q000378:metabolism; D000818:Animals; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000033:anatomy & histology* / Q000378:metabolism; D051379:Mice; D009399:Nephrons / Q000033:anatomy & histology* / Q000378:metabolism; D019700:Thrombospondin 1 / Q000378:metabolism
D042702:Angiopoietin-2; D019700:Thrombospondin 1