Quantitative analysis of intrarenal nerve-associated profiles in the human foetal kidney between 14 and 30 gestational weeks: An S100 immunohistochemical study.

Abstract

Quantitative data on the spatial development of intrarenal S100-positive nerve-associated profiles in human foetal kidneys remain limited, despite the established importance of renal nerves. Building on the previously published semiquantitative observations, this study aimed to generate a quantitative, compartment-resolved map of S100-positive nerve-associated profiles in human foetal kidneys. Formalin-fixed, paraffin-embedded human foetal kidney specimens ranging from 14 to 30 gestational weeks were analysed using S100 immunohistochemistry. Based on gestational age, specimens were divided into three groups: ≤18 gestational weeks (G1, n=6), 19-24 gestational weeks (G2, n=6), and ≥ 25 gestational weeks (G3, n=6). Cortical maturation was assessed by measuring nephrogenic zone and maturation zone thickness and calculating the cortical maturation index (CMI). Morphometric analysis of cortical S100-positive nerve-associated profiles was performed using digital image analysis. Distribution patterns of S100-positive profiles were assessed qualitatively. Group-wise analysis demonstrated significantly lower cortical S100-positive area in G1 compared with G2 and G3 (median: 985 μm² vs. 1733 μm² and 2400 μm², respectively; p < 0.001). Cortical S100-positive area increased significantly with gestational age and foetal weight and showed an inverse correlation with CMI (ρ = -0.410, p < 0.001), indicating parallel progression of S100-positive area and cortical maturation. In multivariate linear regression analyses, cortical S100-positive area remained independently associated with gestational age (β = 125.0, p = 0.006) and foetal weight (β = 1.50, p = 0.006), explaining 57.6% of the variance (adjusted R² = 0.485). Perivascular localisation was the most frequently observed distribution pattern, while juxtaglomerular and intraglomerular patterns were also identified, including in the earliest gestational-age group. This study provides the first quantitative, compartment-resolved analysis of intrarenal nerve-associated profiles in the human foetal kidney. Cortical S100-positive area increases with gestational age in parallel with cortical maturation and shows a predominantly perivascular distribution, consistent with a neurovascular co-development model and establishing a morphological framework for future functional studies of renal innervation.