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29 September 2022 The combined impact of testosterone and Western-style diet on endometriosis severity and progression in rhesus macaques
Cecily V. Bishop, Diana L. Takahashi, Fangzhou Luo, Heather Sidener, Lauren Drew Martin, Lina Gao, Suzanne S. Fei, Jon D. Hennebold, Ov D. Slayden
Author Affiliations +
Abstract

Polycystic ovary syndrome (PCOS) is associated with irregular menstrual cycles, hyperandrogenemia, and obesity. It is currently accepted that women with PCOS are also at risk for endometriosis, but the effect of androgen and obesity on endometriosis has been underexplored. The goal of this study was to determine how testosterone (T) and an obesogenic diet impact the progression of endometriosis in a nonhuman primate (NHP) model. Female rhesus macaques were treated with T (serum levels approximately 1.35 ng/ml), Western-style diet (WSD; 36% of calories from fat compared to 16% in standard monkey chow) or the combination (T + WSD) at the time of menarche as part of a longitudinal study for ∼7 years. Severity of endometriosis was determined based on American Society for Reproductive Medicine (ASRM) revised criteria, and staged 1–4. Stages 1 and 2 were associated with extent of abdominal adhesions, while stages 3 and 4 were associated with presence of chocolate cysts. The combined treatment of T + WSD resulted in earlier onset of endometriosis and more severe types associated with large chocolate cysts compared to all other treatments. There was a strong correlation between glucose clearance, homeostatic model assessment for insulin resistance (HOMA-IR), and total percentage of body fat with presence of cysts, indicating possible indirect contribution of hyperandrogenemia via metabolic dysfunction. An RNA-seq analysis of omental adipose tissue revealed significant impacts on a number of inflammatory signaling pathways. The interactions between obesity, hyperandrogenemia, and abdominal inflammation deserve additional investigation in NHP model species.

Summary Sentence

This nonhuman primate study demonstrates metabolic disturbances associated with exposure to androgens and an obesogenic diet accelerates onset of cystic endometriosis.

© The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Cecily V. Bishop, Diana L. Takahashi, Fangzhou Luo, Heather Sidener, Lauren Drew Martin, Lina Gao, Suzanne S. Fei, Jon D. Hennebold, and Ov D. Slayden "The combined impact of testosterone and Western-style diet on endometriosis severity and progression in rhesus macaques," Biology of Reproduction 108(1), 72-80, (29 September 2022). https://doi.org/10.1093/biolre/ioac183
Received: 20 December 2021; Accepted: 23 September 2022; Published: 29 September 2022
KEYWORDS
endometriosis
metabolism
obesity
polycystic ovary syndrome
testosterone
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