Abstract: FR-PO0922
Antenatal Steroid Exposure Disrupts Renal Lymphatic Maturation and Impairs Postnatal Lymphatic Drainage
Session Information
- Pediatric Nephrology: Genetic Diseases, Development, Neonatal Nephrology, Glomerular Diseases, and More
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1800 Pediatric Nephrology
Authors
- Liang, Haoyang, Tulane University, New Orleans, Louisiana, United States
- Xu, Xiaojiang, Tulane University, New Orleans, Louisiana, United States
- Wang, Yu, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Zhao, Shilin, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Shelton, Elaine L., Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Kon, Valentina, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Yang, Haichun, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Zhong, Jianyong, Vanderbilt University Medical Center, Nashville, Tennessee, United States
Background
Antenatal glucocorticoids are the standard of care for threatened preterm birth but have been linked to long-term renal dysfunction. Although their adverse effects on nephrogenesis are established, steroid impact on developing renal lymphatic system, an essential regulator of tissue fluid clearance and immune cell trafficking, is unknown. We investigated how antenatal dexamethasone (Dex) exposure alters renal lymphatic endothelial cell (LEC) development and lymphatic function.
Methods
Pregnant mice received a single dose of Dex at embryonic day E15.5. These offspring were compared to offspring of dams that did not receive DEX and served as control. Offspring kidneys were evaluated at E17.5, postnatal day 1 (P1), week 2 (W2), and week 4 (W4). To define developmental programming, Prox1+ LECs were isolated from kidneys then underwent bulk RNA sequencing (RNA-seq) followed by pathway analysis and gene set enrichment analysis (GSEA). Renal lymphatic structures were quantified by LYVE-1 immunohistochemistry. Lymphatic function was assessed by Evans Blue clearance in the ear.
Results
In control kidneys, Prox1+ LECs demonstrated a coordinated maturation trajectory from E17.5 to W4, with progressive downregulation of cell cycle and developmental gene programs and upregulation of transport and metabolic pathways. Antenatal Dex exposure disrupted this trajectory across all developmental stages. At E17.5, LECs from antenatal Dex-exposed kidneys were enriched in chromatin organization programs with suppression of core developmental genes. At P1–W2, Dex exposure caused an aberrant re-expression of progenitor-associated programs and signatures consistent with impaired cell cycle progression. By W4, Dex-exposed LECs had persistent dysregulation of extracellular matrix remodeling pathways. Consistent with these molecular changes, kidneys from antenatal Dex-exposure showed enlarged lymphatic vessels on LYVE-1 morphometry and functionally, had impaired lymphatic drainage, evidenced by increased Evans Blue clearance.
Conclusion
Antenatal Dex exposure reprograms renal lymphatic development, producing sustained molecular remodeling, abnormal lymphatic morphology, and impaired drainage. These findings identify the renal lymphatic vasculature as a previously unrecognized target of antenatal steroid exposure revealing a novel mechanism for propensity to long-term susceptibility to kidney dysfunction.
Funding
- NIDDK Support