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Maternal Obesity, Cage Density, and Age Contribute to Prostate Hyperplasia in Mice

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Abstract

Identification of modifiable risk factors is gravely needed to prevent adverse prostate health outcomes. We previously developed a murine precancer model in which exposure to maternal obesity stimulated prostate hyperplasia in offspring. Here, we used generalized linear modeling to evaluate the influence of additional environmental covariates on prostate hyperplasia. As expected from our previous work, the model revealed that aging and maternal diet-induced obesity (DIO) each correlated with prostate hyperplasia. However, prostate hyperplasia was not correlated with the length of maternal DIO. Cage density positively associated with both prostate hyperplasia and offspring body weight. Expression of the glucocorticoid receptor in prostates also positively correlated with cage density and negatively correlated with age of the animal. Together, these findings suggest that prostate tissue was adversely patterned during early life by maternal overnutrition and was susceptible to alteration by environmental factors such as cage density. Additionally, prostate hyperplasia may be acutely influenced by exposure to DIO, rather than occurring as a response to worsening obesity and comorbidities experienced by the mother. Finally, cage density correlated with both corticosteroid receptor abundance and prostate hyperplasia, suggesting that overcrowding influenced offspring prostate hyperplasia. These results emphasize the need for multivariate regression models to evaluate the influence of coordinated variables in complicated animal systems.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Washington University in St Louis, School of Medicine, 425 South Euclid Ave, BJC-IH 10th Floor, Campus Box 8064, 63110, St Louis, MO, USA

    Emily C. Benesh PhD & Kelle H. Moley MD

  2. Division of Public Health Sciences, Department of Surgery, Washington University in St Louis, School of Medicine, St Louis, MO, USA

    Jeff Gill MBA, PhD

  3. Division of Biostatistics, Washington University in St Louis, School of Medicine, St Louis, MO, USA

    Jeff Gill MBA, PhD

  4. Department of Political Science, Washington University in St Louis, One Brookings Dr, St Louis, MO, USA

    Jeff Gill MBA, PhD

  5. Beaumont Health Systems Research Institute, Royal Oak, MI, USA

    Laura E. Lamb PhD

Authors
  1. Emily C. Benesh PhD
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  2. Jeff Gill MBA, PhD
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  3. Laura E. Lamb PhD
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  4. Kelle H. Moley MD
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Correspondence to Kelle H. Moley MD.

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Benesh, E.C., Gill, J., Lamb, L.E. et al. Maternal Obesity, Cage Density, and Age Contribute to Prostate Hyperplasia in Mice. Reprod. Sci. 23, 176–185 (2016). https://doi.org/10.1177/1933719115597767

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