Maturational Regression of Glomeruli Determines the Nephron Population in Normal Mice

BACKGROUND: Regression is an important process in normal development of many organs. In the present 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, 10, 14, 18, 21, 25 and 28 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% CI: 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 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 only valid 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.