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Updated: Jun 12, 2026
A Hyperandrogenic Mouse Model to Study Polycystic Ovary Syndrome
Published on: October 2, 2018
The impact of maternal obesity on polycystic kidney disease progression in a mouse model
Sarah J Miller1, Kaitlyn Hill2, Isabella Darby1
1Department of Internal Medicine, Division of Nephrology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States.
Insights
Maternal obesity did not worsen polycystic kidney disease (PKD) in offspring mice. However, reexposure to a high-fat diet worsened PKD in female offspring, suggesting a diet-dependent effect on disease progression.
Area of Science:
- Nephrology
- Endocrinology
- Developmental Biology
Background:
- The rising prevalence of maternal obesity presents a significant public health concern.
- Obesity is linked to accelerated cyst growth in autosomal dominant polycystic kidney disease (ADPKD).
- The impact of maternal obesity on offspring's polycystic kidney disease (PKD) progression remains largely unknown.
Purpose of the Study:
- To investigate the influence of maternal obesity on the progression of polycystic kidney disease (PKD) in offspring.
- To determine if maternal high-fat diet (HFD) exposure affects PKD severity in Pkd1 mutant mice.
Main Methods:
- Induced maternal obesity using HFD in Pkd1RC/RC mice, an ADPKD model.
- Assessed PKD progression in offspring over one year.
- Reexposed offspring to HFD to evaluate diet-specific effects on disease severity.
Main Results:
- Maternal obesity alone did not significantly alter PKD severity in offspring at 3 months or 1 year of age.
- Reexposure to HFD in adulthood exacerbated PKD in female offspring, indicated by increased cyst index, number, and area.
- Fibrosis and blood urea nitrogen levels were not significantly affected by maternal obesity or refeeding HFD.
Conclusions:
- Maternal obesity during gestation and lactation does not inherently worsen PKD in offspring.
- Post-weaning dietary challenges, specifically HFD reexposure, can accelerate PKD progression in female offspring born to obese mothers.
- These findings highlight a potential sex-specific, diet-mediated acceleration of PKD in offspring of obese mothers.
Abstract:
Due to the growing obesity epidemic in the United States, it is now estimated that approximately one third of all children are born to obese moms. These data, coupled with data indicating that obesity is associated with accelerated cyst growth in patients with autosomal dominant polycystic kidney disease (ADPKD), led us to hypothesize that maternal obesity may influence the rate of disease progression in offspring. To test this hypothesis, we induced maternal obesity by high-fat diet (HFD) feeding in the orthologous Pkd1RC/RC mouse model of ADPKD and followed polycystic kidney disease (PKD) progression in offspring for up to 1 year. Surprisingly, and in contrast to our initial hypothesis, exposure to maternal obesity during pregnancy and lactation did not significantly impact PKD severity in offspring at 3 mo or 1 yr of age. In contrast, reexposure to HFD for ∼3 m beginning at 12 wk of age worsened PKD severity in female, but not male, offspring born to obese dams as measured by cystic index, cyst number, and cyst area. Despite worsened cystic parameters, fibrosis and blood urea nitrogen were not altered in these animals. Collectively, these findings indicate that maternal obesity may accelerate PKD severity in female offspring exposed to an obesogenic diet.NEW & NOTEWORTHY Due to the growing obesity pandemic, almost one third of all children are born to mothers with obesity; however, the impact of maternal obesity on polycystic kidney disease (PKD) is unknown. In this manuscript, we found that maternal obesity did not worsen PKD severity in Pkd1RC/RC mice at 3 mo or 1 yr of age when weaned onto normal chow diet. However, rechallenging pups born to obese mothers worsened PKD severity in female but not male mice.
