Pyelonephritis is associated with persistent alterations in immune-stromal and vascular programs in the human placenta
- 1University of California, San Francisco
Abstract
Maternal systemic infection during pregnancy is associated with placental dysfunction even when pathogens do not directly invade the placenta, but the cellular pathways linking antecedent infection to persistent placental alterations remain poorly defined. Here we used spatial transcriptomics to resolve trophoblast-, fetal endothelial, and Hofbauer cell-enriched niches in placentas collected at term after clinical recovery from antepartum pyelonephritis. We profiled 168 spatially defined areas from 14 placentas and integrated transcriptional findings with blinded histopathology and quantitative extracellular matrix analysis. Pyelonephritis was associated with strikingly compartment-specific transcriptional responses. Hofbauer cell-enriched niches showed the most extensive alterations, with coordinated enrichment of extracellular matrix remodeling and vascular developmental programs, including increased ELN expression (log2FC = 0.84, FDR = 0.033) and increased expression of genes governing collagen deposition, elastic-fiber assembly, matrix maturation and turnover. Quantitative analysis of 1,790 fetal vessels independently identified altered perivascular matrix composition, with Hofbauer cell-enriched ELN expression correlating with greater perivascular elastin content ({rho} = 0.67, P = 0.008). Fetal endothelial-enriched regions exhibited complementary alterations in vascular remodeling and endothelial identity, including increased PLAC8 (log2FC = 1.36, FDR = 0.047), whereas trophoblast-enriched regions showed little detectable transcriptional response. Histopathology further demonstrated increased lesions associated with maternal vascular malperfusion and perivillous fibrin deposition. Together, these findings identify the villous immune-stromal-vascular microenvironment as a persistent site of placental remodeling following maternal infection and suggest that clinical recovery from maternal illness may not coincide with normalization of placental biology.
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BibTeX
@misc{blauvelt2026pyelonephritis,
title = {{Pyelonephritis is associated with persistent alterations in immune-stromal and vascular programs in the human placenta}},
author = {C. Blauvelt and N. Ozarslan and S. M. Tsoi and O. Trush and C. Taylor and S. Buarpung and M. Chidboy and J. S. Esteban and A. Morales and C. A. Mong and N. Rahseparian and C. Gasper and J. F. Robinson and E. E. Crouch and S. L. Gaw},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.05.26364820},
url = {https://www.medrxiv.org/content/10.64898/2026.10.05.26364820v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Pyelonephritis is associated with persistent alterations in immune-stromal and vascular programs in the human placenta
AU - C. Blauvelt
AU - N. Ozarslan
AU - S. M. Tsoi
AU - O. Trush
AU - C. Taylor
AU - S. Buarpung
AU - M. Chidboy
AU - J. S. Esteban
AU - A. Morales
AU - C. A. Mong
AU - N. Rahseparian
AU - C. Gasper
AU - J. F. Robinson
AU - E. E. Crouch
AU - S. L. Gaw
PY - 2026
DA - 2026/10/05
PB - medRxiv
DO - 10.64898/2026.10.05.26364820
UR - https://www.medrxiv.org/content/10.64898/2026.10.05.26364820v1
AB - Maternal systemic infection during pregnancy is associated with placental dysfunction even when pathogens do not directly invade the placenta, but the cellular pathways linking antecedent infection to persistent placental alterations remain poorly defined. Here we used spatial transcriptomics to resolve trophoblast-, fetal endothelial, and Hofbauer cell-enriched niches in placentas collected at term after clinical recovery from antepartum pyelonephritis. We profiled 168 spatially defined areas from 14 placentas and integrated transcriptional findings with blinded histopathology and quantitative extracellular matrix analysis. Pyelonephritis was associated with strikingly compartment-specific transcriptional responses. Hofbauer cell-enriched niches showed the most extensive alterations, with coordinated enrichment of extracellular matrix remodeling and vascular developmental programs, including increased ELN expression (log2FC = 0.84, FDR = 0.033) and increased expression of genes governing collagen deposition, elastic-fiber assembly, matrix maturation and turnover. Quantitative analysis of 1,790 fetal vessels independently identified altered perivascular matrix composition, with Hofbauer cell-enriched ELN expression correlating with greater perivascular elastin content ({rho} = 0.67, P = 0.008). Fetal endothelial-enriched regions exhibited complementary alterations in vascular remodeling and endothelial identity, including increased PLAC8 (log2FC = 1.36, FDR = 0.047), whereas trophoblast-enriched regions showed little detectable transcriptional response. Histopathology further demonstrated increased lesions associated with maternal vascular malperfusion and perivillous fibrin deposition. Together, these findings identify the villous immune-stromal-vascular microenvironment as a persistent site of placental remodeling following maternal infection and suggest that clinical recovery from maternal illness may not coincide with normalization of placental biology.
ER -