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Ovariectomy Affects Acute Pancreatitis in Mice

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Abstract

Background

Serum estradiol levels in severe acute injury are correlated with in hospital mortality. In acute pancreatitis, serum estradiol levels are strong predictors of disease severity. Studies of whether changes in estradiol levels play a causative role in acute pancreatitis severity are limited. The ovariectomized mouse model has been used to study the effects of estradiol in health and disease.

Aims

We assessed whether the ovariectomized mouse model could be used to assess the effects of estradiol on pancreatitis severity.

Methods

C57BL/6 mice with their ovaries removed were used to simulate low circulating estradiol conditions. Ovariectomized mice were treated with six hourly injections of cerulein to induce mild acute pancreatitis and compared to ovariectomized mice pre-treated with subcutaneous estradiol injections.

Results

Findings suggest ovariectomized model is a problematic preparation to study pancreatitis. At baseline, ovariectomy leads to prominent acinar cell ultrastructure changes as well as changes in other select morphologic and biomarkers of pancreatitis. In addition, ovariectomy changed select acute pancreatitis responses that were only partially rescued by estradiol pre-treatment.

Conclusions

These findings suggest that the ovariectomized mouse as a model of estradiol depletion should be used with caution in pancreatic studies. Future studies should explore whether derangements in other female hormones produced by the ovaries can lead to changes in pancreatic studies.

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Data availability

All data generated or analyzed in this study are included in this published article.

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Acknowledgments

We would like to thank Thomas Pointer for his assistance in study design.

Funding

This study was funded by NIH Medical Student Fellowship to MW (DK007017) and a Veterans Administration Merit Award to FG (BX-003250).

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Authors and Affiliations

  1. Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA

    Melinda Wang & Fred Gorelick

  2. West Haven VA Medical Center-VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT, 06515, USA

    Melinda Wang & Fred Gorelick

Authors
  1. Melinda Wang
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  2. Fred Gorelick
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Contributions

MW performed data acquisition, data interpretation and statistical analysis. MW and FG performed study concept, design, writing, review, and paper revision.

Corresponding author

Correspondence to Melinda Wang.

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Conflict of interest

The authors have no competing interests to report.

Consent to publish

No human participants were included in this study, and consent to publish was not required.

Ethics approval

All animals and procedures within this study were in compliance by the Animal Welfare Act, the Public Health Service Policy, and the Guide for the Care and Use of Laboratory Animals. This research protocol was approved by the Veterans Health Administration Institutional Animal Care and Use Committee (FG009, West Haven, CT, USA).

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Wang, M., Gorelick, F. Ovariectomy Affects Acute Pancreatitis in Mice. Dig Dis Sci 67, 2971–2980 (2022). https://doi.org/10.1007/s10620-021-07116-w

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  • DOI: https://doi.org/10.1007/s10620-021-07116-w

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