Abstract: FR-OR93
Pregnancy Protects against Kidney Injury in Aged Female Mice Lacking G Protein-Coupled Estrogen Receptor
Session Information
- Women's Health and Kidney Diseases: From Bench to Bedside
October 25, 2024 | Location: Room 24, Convention Center
Abstract Time: 04:50 PM - 05:00 PM
Category: Women's Health and Kidney Diseases
- 2200 Women's Health and Kidney Diseases
Authors
- Singh, Ravneet, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Almutlaq, Rawan N., University of Alabama at Birmingham, Birmingham, Alabama, United States
- Sugahara, Sho, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Brooks, Craig R., Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Curtis, Lisa M., University of Alabama at Birmingham, Birmingham, Alabama, United States
- Gohar, Eman Y., Vanderbilt University Medical Center, Nashville, Tennessee, United States
Background
Chronic kidney disease affects more than 1 in 7 US adults, with prevalence increasing with age. In particular, kidney disease is one of the top ten leading causes of death for women. In female rodents, estrogen elicits protective responses against various kidney injuries through G protein-coupled estrogen receptor 1 (GPER1). GPER1-induced vasodilation in rats is increased with pregnancies.The impact of GPER1 signaling and pregnancy on long-term renal health is not clear yet. We hypothesized that GPER1 and previous pregnancies (PP) protect against kidney injury in aged female mice.
Methods
In our study, we used 16-20 month-old GPER1 wild-type (WT) and global knock-out (KO) female mice with or without a history of PP (n=6-8/group). We collected 24-hour urine samples, plasma, and kidneys. Urinary levels of kidney injury biomarkers including protein, albumin, nephrin (glomerular injury marker), kidney injury molecule 1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL, tubular injury marker) were measured. Plasma creatinine levels were measured. Kidney sections were stained for KIM-1 and assessed for apoptosis by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay.
Results
Urinary protein, albumin and plasma creatinine were elevated and PP eliminated this difference. In aged virgin GPER1 KO mice urinary excretion of nephrin [0.63±0.12 vs. 0.36±0.07 ng/day; p=0.0488], KIM-1 [3.11±0.59 vs. 0.79±0.29 ng/day; p=0.0004], and NGAL [208.48±28.17 vs.70.55±11.32; ng/day; p<0.0001] was increased. However, aged previously pregnant KO mice elicited lower levels of excretion of nephrin [0.295±0.04 ng/day; p= 0.0159], KIM-1 [1.38±0.28 ng/day; p=0.0058], and NGAL [67.06±15.69 ng/day; p<0.0001] compared to virgin KO mice. More KIM-1 positive tubules were identified in the aged virgin KO mice compared to the aged virgin WT mice. Further, GPER1 deletion increased TUNEL-positive nuclei in the renal cortex of the virgin mice [662±42 vs. 407±30; p=0.0002]. This genotypic difference was blunted with PP [282±12; p<0.0001].
Conclusion
Our data indicates that GPER1 and former pregnancies protect from kidney injury in aged female mice. This data could provide insight into the development of renoprotective therapeutic agents for postmenopausal women.
Funding
- NIDDK Support