Abstract: FR-PO0974
Renal Transcriptome During Pregnancy Shows Extensive Deregulation in Acute and Chronic Mouse Injury Models
Session Information
- Women's Health and Kidney Diseases
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Women's Health and Kidney Diseases
- 2100 Women's Health and Kidney Diseases
Authors
- Jankowski, Jakub, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
- Hennighausen, Lothar, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
Background
During gestation, kidneys are subject to additional stress as they are under increased external pressure and expand to accommodate elevated blood flow and filtration rate. Moreover, common complications like pre-eclampsia and diabetes directly affect renal function. Despite that, there are no human datasets available describing the underlying changes in renal transcriptomic landscape, as renal biopsies in pregnancy are incredibly rare. Our study bridges this gap by providing mouse maternal transcriptomic data at the baseline and in acute and fibrotic injury models.
Methods
Female mouse kidneys were collected at day 18 of pregnancy (P18) and day 10 of lactation (L10), with nulliparous (N) mice used as controls. We used bulk RNA-seq to show baseline deregulated genes (DEGs). Next, we performed bilateral warm renal ischemia-reperfusion injury (n=6, IRI, 30’ hypoxia, 24h reperfusion) in N, P17 and L9 mice. We assessed renal function through histology and plasma creatinine measurements, and mRNA expression with qPCR and bulk RNA-seq. Lastly, we used 30’ unilateral IRI model in N and P17 mice (n=5) and investigated renal fibrosis and transcriptome after 28 days.
Results
P18 and L10 mice showed 135 and 96 DEGs respectively compared to N at the baseline. They were largely linked to cell proliferation, but also estrogen response and JAK/STAT signaling. 24 hours after acute injury there was no difference in plasma creatinine between IRI groups (mean = 0.27 (N), 0.32 (P10), 0.24 mg/dl (L10)). Injury induction was confirmed via qPCR, with increased Havcr1 expression compared to baseline (mean fold change = 1551 (N), 1997 (P10), 2408 (L10)). RNA-seq showed 1204 DEGs in N vs. P18 IRI groups, but only 7 in N vs. L10. No differences in renal fibrosis were observed in N vs. P17 mice on day 28 as indicated by Masson Trichrome and qPCR of Acta2 and Tgfb. While we found only 7 DEGs in P17 contralateral vs injured kidney, there were 299 in the N group.
Conclusion
While the injury didn’t overtly affect renal function and fibrosis, its effects on gene expression in the pregnant kidney were extensive. Our datasets allow for investigation of gestational genes which react acutely to injury or remain deregulated long-term in either healthy or ischemia-impacted pregnancy. We hope our results prompt identification of targetable pathways to alleviate the current maternal mortality and morbidity rates.
Funding
- NIDDK Support