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Altered hormone and bioactive lipid plasma profile in rodent models of polycystic ovarian syndrome revealed by targeted mass spectrometry

Abstract:

Background: Polycystic ovarian syndrome (PCOS) symptoms include excessive body or facial hair, irregular periods, reduced fertility, and reoccurring pregnancy loss. Hyperandrogenism and chronic inflammation are hallmarks of PCOS, which is diagnosed by analyzing steroid hormones in the blood. Studies suggest that bioactive lipids are contributing to chronic inflammation.

Methods: To research PCOS, animal models, such as letrozole- and dihydrotestosterone-treated rats, are used. They display similar ovarian and metabolic characteristics, although plasma lipid profiles have not been determined. Therefore, in order to validate the use of these models for PCOS, we have optimized a mass spectrometry-based targeted lipidomics workflow, which increases the sensitivity of measuring these lipids in rat plasma.

Results: Our analysis shows that letrozole caused a significant elevation of 5α-androstene-3,17-dione and testosterone. Dihydrotestosterone treatment resulted in increased dehydroepiandrosterone-sulphate and allopregnanolone but a reduction in testosterone, progesterone, pregnenolone, and D-sphingosine. In both models, 25-hydroxycholesterol and leukotriene C4 were significantly diminished, and 4-cholesten-3-one was significantly increased, and these particular metabolites are not known to be changed in human PCOS.

Conclusion: These results suggest that the plasma lipids of these rodent models exert altered profiles of sterols, leukotrienes and steroid hormones akin to human PCOS but with notable differences.

Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.14740/jem1042

Authors

More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Target Discovery Institute
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDORMS
Sub department:
Botnar Institute for Musculoskeletal Sciences
Role:
Author
ORCID:
0000-0003-3632-0084
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Target Discovery Institute
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Target Discovery Institute
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Target Discovery Institute
Role:
Author


Publisher:
Elmer Press
Journal:
Journal of Clinical Endocrinology and Metabolism More from this journal
Volume:
15
Issue:
1
Pages:
1-14
Publication date:
2025-03-14
Acceptance date:
2025-02-18
DOI:
EISSN:
1923-287X
ISSN:
1923-2861


Language:
English
Keywords:
Pubs id:
2097193
Local pid:
pubs:2097193
Deposit date:
2025-03-31
ARK identifier:

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