Development of the Human Fetal Kidney from Mid to Late Gestation in Male and Female Infants

Abstract

Background: During normal human kidney development, nephrogenesis (the formation of nephrons) is complete by term birth, with the majority of nephrons formed late in gestation. The aim of this study was to morphologically examine nephrogenesis in fetal human kidneys from 20 to 41weeks of gestation.

Methods: Kidney samples were obtained at autopsy from 71 infants that died acutely in utero or within 24h after birth. Using image analysis, nephrogenic zone width, the number of glomerular generations, renal corpuscle cross-sectional area and the cellular composition of glomeruli were examined. Kidneys from female and male infants were analysed separately.

Findings: The number of glomerular generations formed within the fetal kidneys was directly proportional to gestational age, body weight and kidney weight, with variability between individuals in the ultimate number of generations (8 to 12) and in the timing of the cessation of nephrogenesis (still ongoing at 37weeks gestation in one infant). There was a slight but significant (r²=0.30, P=0.001) increase in renal corpuscle cross-sectional area from mid gestation to term in females, but this was not evident in males. The proportions of podocytes, endothelial and non-epithelial cells within mature glomeruli were stable throughout gestation.

Interpretation: These findings highlight spatial and temporal variability in nephrogenesis in the developing human kidney, whereas the relative cellular composition of glomeruli does not appear to be influenced by gestational age.

Keywords: Glomerulus; Kidney development; Nephrogenesis; Podocyte.

Fig. 1

Changes in renal morphology throughout gestation. Representative images of haematoxylin and eosin-stained sections of renal cortex from male (a–e) and female (f–j) fetuses at 21 (a) 22 (f), 26 (b) 25 (g), 30 (c, h), 36 (d, i), and 40 (e, j) weeks of gestation. Scale bar = 100 μm.

Fig. 2

Nephrogenic zone width. (a) Representative image of the nephrogenic zone, the area of nephron formation in the outer renal cortex (indicated by dotted line and arrow), in a kidney from a stillborn fetus at 30 weeks of gestation. Scale bar = 100 μm. (b) Linear regression analysis of nephrogenic zone width versus gestational age in female (O) and male (□) infants from 20 to 41 weeks of gestation.

Fig. 3

Variability in the timing of cessation of nephrogenesis. Light photomicrographs of haematoxylin and eosin stained sections of the outer renal cortex from two fetuses that died acutely in utero at 37 weeks of gestation. (a) Nephrogenesis is ongoing in the outer renal cortex (S-shaped body shown in the bracket); (b) nephrogenesis has ceased. Scale bar = 50 μm.

Fig. 4

Number of glomerular generations. Representative images of medullary rays (dotted lines) and generations of glomeruli (circled) in haematoxylin and eosin-stained sections of renal cortex from fetuses at (a) 22 weeks of gestation (4 glomerular generations formed) and (b) 33 weeks of gestation (9 glomerular generations formed). Scale bar = 100 μm. Linear regression analyses of the number of glomerular generations formed within the kidney versus gestational age (c), kidney weight (d) and body weight (e) in female (O) and male (■) infants.

Fig. 5

Renal corpuscle size. Representative images of renal corpuscles from male (a) and female (b) fetuses at 23 weeks of gestation, and male (c) and female (d) fetuses at term. Linear regresion analysis of renal corpuscle cross-sectional area versus gestational age (e), kidney weight (f), body weight (g) and the number of glomerular generations (h) in female (O) and male (□) infants.

Fig. 6

Cellular composition of glomeruli. Representative images of glomerular cross-sections from the kidneys of stillborn fetuses at (a) 22 (b) 33 and (c) 39 weeks of gestation. Podocytes were immuno-labelled with WT-1 (green), endothelial cells were immuno-labelled with vWF (red) and nuclei were labelled with DAPI (blue). Scale bar = 50 μm. Linear regression analysis of the average number of podocytes, endothelial cells and non-epithelial (mesangial) cells per glomerular cross-section in female (d) and male (e) infants versus gestational age. Each data point represents the average of 50 glomeruli per kidney. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)