Kidney morphological changes associated with early-life carbonaceous ultrafine particle exposure: A pathomics approach

Background: Fine particulate matter (<2.5 μm, PM_2.5), and its subcomponent ultrafine carbonaceous particles (UFP), have been shown to cause adverse health effects, including respiratory and cardiovascular disease, and decline in kidney function. Previous research demonstrated the presence of these particles in the kidney, yet potential effects on kidney tissue remain elusive. Methods: We exposed wild-type C57BL/6J mice to either HEPA-filtered air or clean ultrafine carbonaceous particles (UFP^C, 450 μg/m³) during the prenatal (gestational day 8–9 + 16–17) and/or postnatal (PND 4–7 + 10–13) phase, with an additional re-exposure on PND 142–145 of the exposed animals, and harvested kidney tissue on PND 181–182. Large-scale histomorphometry (pathomics) was utilized to quantify the effects of exposure to UFP^C on kidney tissue morphology. Here, we quantified an average (SD) of 205 (56) arteries, 113 (15) glomeruli, and 6966 (887) tubules in each group. Differences between exposure groups were assessed using the Kruskal-Wallis tests. UFP^C were detected using non-incandescent white light generation under femtosecond-pulsed illumination. Correlations between measured UFP^C and morphometric features were evaluated with Pearson's correlation coefficient. Results: Compared to the sham group, the pre- and postnatally exposed group had significantly smaller cortical and larger medullary areas (p < 0.05). The postnatally exposed group had more glomeruli in comparison to the sham group (p < 0.01). The prenatally exposed group showed lower tubular area and altered tubular shapes, with reduced circularity and solidity (p < 0.02). The prenatally exposed and pre- and postnatally exposed groups showed higher percentages of the interstitial area (p < 0.05). Correlation analysis revealed positive associations between UFP^C exposure and tubular morphometric features, while negative correlations were found with interstitial area percentage; no significant correlations were noted for glomerular or arteriolar features. Conclusions: This study shows the impact of UFP^C exposure on kidney morphology with altered overall cortical and medullary areas and altered tubular and interstitial structures. These structural alterations may potentially increase kidney vulnerability to injury, underscoring the need for further studies to assess the long-term impact of environmental pollutants on kidney health.