Abstract: FR-PO385
Altering Maternal Macronutrient Supply Can Extend Nephrogenesis and Rescue Nephron Endowment
Session Information
- Genetics, Development, Regeneration
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Development‚ Stem Cells‚ and Regenerative Medicine
- 500 Development‚ Stem Cells‚ and Regenerative Medicine
Authors
- Bertram, John F., Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia
- Gazzard, Sarah E., Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia
- Moreau, Julie Liliane, Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia
- Eliades, Joel Alex, Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia
- Combes, Alexander N., Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia
- Simpson, Stephen J., Charles Perkins Centre Research and Education Hub, The University of Sydney, Sydney, New South Wales, Australia
- Cullen-McEwen, Luise A., Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia
Background
Human and animal studies have linked low nephron endowment with increased risk of chronic kidney disease and hypertension in later life. Strategies to increase nephron endowment in those at risk of a nephron deficit are therefore sought. We have previously shown that feeding pregnant mice a low carbohydrate high fat diet (LCHFD) boosts offspring nephron endowment. The present study investigated the mechanism behind this increased nephron endowment and whether the maternal LCHFD could rescue a programmed nephron deficit.
Methods
To examine the mechanism behind the increased nephron endowment C57Bl6 pregnant mice were fed a normal diet (ND) or LCHFD until postnatal day (PN) 0 (to assess numbers of Six2+ nephrogenic niches) or PN2-7 (to assess the timing of cessation of nephrogenesis). To examine whether the LCHFD could rescue a programmed nephron deficit, a cohort of pregnant mice were fed either a ND, LCHFD or a low protein diet (LPD) from mating and throughout gestation and lactation, or LPD from mating and throughout gestation and then switched to the LCHFD at birth. At PN21 we estimated nephron endowment using unbiased stereology. Food intakes were measured throughout pregnancy and lactation to assess total caloric intake.
Results
At birth, the number of nephrogenic niches and nephrons in LCHFD offspring was similar to ND offspring indicating the augmentation of nephron number occurs postnatally during lactation. At PN3, nephron induction was complete in ND mice, however in LCHFD offspring Six2+ nephron progenitor cells were still present. Similarly, at PN6 the nephrogenic zone was absent in ND offspring but remained in LCHFD offspring indicating a prolonged nephrogenic period. At PN21, LPD mice contained 9770±417 nephrons per kidney while ND mice contained 13143±270 nephrons per kidney (p<0.0001). Offspring of mothers fed the LPD diet and then switched to the LCHFD contained 13455±403 nephrons (p<0.0001 compared with LPD) demonstrating the diet switch at birth prevented the nephron deficit. Food intake analyses indicated the increased caloric density of the LCHFD was not responsible for the augmentation of nephron number.
Conclusion
These findings indicate that maternal nutrition, via lactation, can rescue nephron endowment in mice destined to develop kidneys with a nephron deficit.