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

Abstract

BackgroundDuring 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 41 weeks of gestation.MethodsKidney samples were obtained at autopsy from 71 infants that died acutely in utero or within 24 h 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.FindingsThe 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 37 weeks 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.InterpretationThese 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.

Shaping of the nephron – a complex, vulnerable, and poorly explored backdrop for noxae impairing nephrogenesis in the fetal human kidney

“…The inner border of the nephrogenic zone (Table 1) This represents the demarcation line, where the late Sshaped body as the last stage of nephron anlage starts with the maturing process to become a fully functional nephron. In gestational controls, the width of the nephrogenic zone can be up to 150 μm, and in the group of preterm babies, it is significantly smaller at 100 μm [28,29].…”

“…The outer border of the nephrogenic zone faces the inner side of the renal capsule ( Fig. 1), while the inner border lines along the proximal (medulla-orientated) pole of an Sshaped body [28,29,40].…”

Fate-mapping within human kidney organoids reveals conserved mammalian nephron progenitor lineage relationships

“…In the developing kidney in vivo, new nephrons arise throughout fetal development, arising from a self-renewing Six2 + nephron progenitor population present around the tips of the ureteric epithelium (Kobayashi et al, 2008). This process continues until approximately week 36 in human (Hinchliffe et al, 1991;Ryan et al, 2018) and the first few days after birth in mouse (Rumballe et al, 2011), at which point all NPC have committed to nephron formation. To determine the duration of nephrogenesis across the period of kidney organoid culture, we generated SIX2 knock-in iPSCs using the tamoxifen-inducible Cre recombinase, CreERT2 (Indra et al, 1999).…”

A practical guide to the stereological assessment of glomerular number, size, and cellular composition

“…Blood is filtered through the glomerular filtration barrier, which is composed of the fenestrated endothelium, a basement membrane, and the interdigitating foot processes of the podocytes. Importantly, glomeruli are only formed in early development, with no new glomeruli formed after term birth in humans (Hinchliffe, Sargent, Howard, Chan, & van Velzen, 1991;Ryan et al, 2018;. Likewise, podocytes are post-mitotic cells that do not have the capacity to proliferate after birth, and have a limited capacity for replacement by progenitor cells following injury (Greka & Mundel, 2012;Lasagni et al, 2015;Wanner et al, 2014).…”