Dehydroepiandrosterone-induced polycystic ovary syndrome mouse model requires continous treatments to maintain reproductive phenotypes

Abstract Background Polycystic ovary syndrome (PCOS) is the most common endocrinopathy associated with infertility and metabolic disorder in women of reproductive age. Animal models have been developed and used as tools to unravel the pathogenesis of PCOS, among which most postnatal models employ co...

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Main Authors: Haowen Wu, Bining Zhao, Qiyang Yao, Jihong Kang
Format: Article
Language:English
Published: BMC 2023-10-01
Series:Journal of Ovarian Research
Subjects:
Online Access:https://doi.org/10.1186/s13048-023-01299-8
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author Haowen Wu
Bining Zhao
Qiyang Yao
Jihong Kang
author_facet Haowen Wu
Bining Zhao
Qiyang Yao
Jihong Kang
author_sort Haowen Wu
collection DOAJ
description Abstract Background Polycystic ovary syndrome (PCOS) is the most common endocrinopathy associated with infertility and metabolic disorder in women of reproductive age. Animal models have been developed and used as tools to unravel the pathogenesis of PCOS, among which most postnatal models employ continuing experimental manipulations. However, the persistence and stability of these animals after modeling is unknown. Dehydroepiandrosterone (DHEA)-induced PCOS mouse model is commonly used in PCOS studies. Thus the aim of the present study was to investigate the reproductive features of DHEA-induced PCOS mice fed a normal chow or an high-fat diet (HFD) with treatment withdrawal or consecutive treatments after PCOS mouse models were established. Methods Prepubertal C57BL/6 J mice (age 25 days) were injected (s.c.) daily with DHEA on a normal chow or a 60% HFD for 20 consecutive days to induce PCOS mouse models. Mice injected with the vehicle sesame oil were used as controls. After 20 days, mice were divided into 2 groups, namely “Continue dosing group” and “Stop dosing group”. The animals were consecutively treated with DHEA or DHEA + HFD, or housed without any treatment for 2 or 4 weeks. Estrous cycles were evaluated during this period. At the end of the experiment, serum testosterone (T) levels were measured and the morphology of ovaries was evaluated. Results The mice in Continue dosing groups maintained reproductive phenotypes of PCOS mouse models. In contrast, 2 or 4 weeks after PCOS models were established, the mice with treatment withdrawal in Stop dosing groups exhibited normal serum testosterone levels, regular estrous cycle, and relatively normal ovarian morphology. In addition, even with consecutive treatments, there was no marked difference in body weight between DHEA mice on the normal chow or an HFD in Continue dosing groups and the control animals 3 weeks after modeling. Conclusions After PCOS mice were induced with DHEA or DHEA + HFD, the mice still need consecutive treatments to maintain reproductive phenotypes to be regarded as PCOS mice that meet the diagnostic criteria of PCOS defined by the 2003 Rotterdam criteria.
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spelling doaj.art-88b5702d562b4393910bfff1cb42b8bc2023-11-20T10:32:35ZengBMCJournal of Ovarian Research1757-22152023-10-011611910.1186/s13048-023-01299-8Dehydroepiandrosterone-induced polycystic ovary syndrome mouse model requires continous treatments to maintain reproductive phenotypesHaowen Wu0Bining Zhao1Qiyang Yao2Jihong Kang3Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science CenterDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science CenterDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science CenterDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science CenterAbstract Background Polycystic ovary syndrome (PCOS) is the most common endocrinopathy associated with infertility and metabolic disorder in women of reproductive age. Animal models have been developed and used as tools to unravel the pathogenesis of PCOS, among which most postnatal models employ continuing experimental manipulations. However, the persistence and stability of these animals after modeling is unknown. Dehydroepiandrosterone (DHEA)-induced PCOS mouse model is commonly used in PCOS studies. Thus the aim of the present study was to investigate the reproductive features of DHEA-induced PCOS mice fed a normal chow or an high-fat diet (HFD) with treatment withdrawal or consecutive treatments after PCOS mouse models were established. Methods Prepubertal C57BL/6 J mice (age 25 days) were injected (s.c.) daily with DHEA on a normal chow or a 60% HFD for 20 consecutive days to induce PCOS mouse models. Mice injected with the vehicle sesame oil were used as controls. After 20 days, mice were divided into 2 groups, namely “Continue dosing group” and “Stop dosing group”. The animals were consecutively treated with DHEA or DHEA + HFD, or housed without any treatment for 2 or 4 weeks. Estrous cycles were evaluated during this period. At the end of the experiment, serum testosterone (T) levels were measured and the morphology of ovaries was evaluated. Results The mice in Continue dosing groups maintained reproductive phenotypes of PCOS mouse models. In contrast, 2 or 4 weeks after PCOS models were established, the mice with treatment withdrawal in Stop dosing groups exhibited normal serum testosterone levels, regular estrous cycle, and relatively normal ovarian morphology. In addition, even with consecutive treatments, there was no marked difference in body weight between DHEA mice on the normal chow or an HFD in Continue dosing groups and the control animals 3 weeks after modeling. Conclusions After PCOS mice were induced with DHEA or DHEA + HFD, the mice still need consecutive treatments to maintain reproductive phenotypes to be regarded as PCOS mice that meet the diagnostic criteria of PCOS defined by the 2003 Rotterdam criteria.https://doi.org/10.1186/s13048-023-01299-8Polycystic ovary syndromePhenotype maintenanceTreatment withdrawal
spellingShingle Haowen Wu
Bining Zhao
Qiyang Yao
Jihong Kang
Dehydroepiandrosterone-induced polycystic ovary syndrome mouse model requires continous treatments to maintain reproductive phenotypes
Journal of Ovarian Research
Polycystic ovary syndrome
Phenotype maintenance
Treatment withdrawal
title Dehydroepiandrosterone-induced polycystic ovary syndrome mouse model requires continous treatments to maintain reproductive phenotypes
title_full Dehydroepiandrosterone-induced polycystic ovary syndrome mouse model requires continous treatments to maintain reproductive phenotypes
title_fullStr Dehydroepiandrosterone-induced polycystic ovary syndrome mouse model requires continous treatments to maintain reproductive phenotypes
title_full_unstemmed Dehydroepiandrosterone-induced polycystic ovary syndrome mouse model requires continous treatments to maintain reproductive phenotypes
title_short Dehydroepiandrosterone-induced polycystic ovary syndrome mouse model requires continous treatments to maintain reproductive phenotypes
title_sort dehydroepiandrosterone induced polycystic ovary syndrome mouse model requires continous treatments to maintain reproductive phenotypes
topic Polycystic ovary syndrome
Phenotype maintenance
Treatment withdrawal
url https://doi.org/10.1186/s13048-023-01299-8
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AT qiyangyao dehydroepiandrosteroneinducedpolycysticovarysyndromemousemodelrequirescontinoustreatmentstomaintainreproductivephenotypes
AT jihongkang dehydroepiandrosteroneinducedpolycysticovarysyndromemousemodelrequirescontinoustreatmentstomaintainreproductivephenotypes