Effects of Androgen Excess-Related Metabolic Disturbances on Granulosa Cell Function and Follicular Development

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease in women of reproductive age. Ovarian dysfunction including abnormal steroid hormone synthesis and follicular arrest play a vital role in PCOS pathogenesis. Hyperandrogenemia is one of the important characteristics of PCOS. However, the mechanism of regulation and interaction between hyperandrogenism and ovulation abnormalities are not clear. To investigate androgen-related metabolic state in granulosa cells of PCOS patients, we identified the transcriptome characteristics of PCOS granulosa cells by RNA-seq. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes (DEGs) revealed that genes enriched in lipid metabolism pathway, fatty acid biosynthetic process and ovarian steroidogenesis pathway were abnormally expressed in PCOS granulosa cells in comparison with that in control. There are close interactions among these three pathways as identified by analysis of the protein-protein interaction (PPI) network of DEGs. Furthermore, in vitro mouse follicle culture system was established to explore the effect of high androgen and its related metabolic dysfunction on follicular growth and ovulation. RT-qPCR results showed that follicles cultured with dehydroepiandrosterone (DHEA) exhibited decreased expression levels of cumulus expansion-related genes ( Has2, Ptx3, Tnfaip6 and Adamts1) and oocyte maturation-related genes ( Gdf9 and Bmp15), which may be caused by impaired steroid hormone synthesis and lipid metabolism, thus inhibited follicular development and ovulation. Furthermore, the inhibition effect of DHEA on follicle development and ovulation was ameliorated by flutamide, an androgen receptor (AR) antagonist, suggesting the involvement of AR signaling. In summary, our study offers new insights into understanding the role of androgen excess induced granulosa cell metabolic disorder in ovarian dysfunction of PCOS patients.

Related collections

Most cited references 49

Record: found
Abstract: found
Article: not found

Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment

Héctor F. Escobar-Morreale (2018)

Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic disorders in premenopausal women. Heterogeneous by nature, PCOS is defined by a combination of signs and symptoms of androgen excess and ovarian dysfunction in the absence of other specific diagnoses. The aetiology of this syndrome remains largely unknown, but mounting evidence suggests that PCOS might be a complex multigenic disorder with strong epigenetic and environmental influences, including diet and lifestyle factors. PCOS is frequently associated with abdominal adiposity, insulin resistance, obesity, metabolic disorders and cardiovascular risk factors. The diagnosis and treatment of PCOS are not complicated, requiring only the judicious application of a few well-standardized diagnostic methods and appropriate therapeutic approaches addressing hyperandrogenism, the consequences of ovarian dysfunction and the associated metabolic disorders. This article aims to provide a balanced review of the latest advances and current limitations in our knowledge about PCOS while also providing a few clear and simple principles, based on current evidence-based clinical guidelines, for the proper diagnosis and long-term clinical management of women with PCOS.

0 comments Cited 497 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Polycystic ovary syndrome.

Ricardo Azziz, Enrico Carmina, ZiJiang Chen … (2016)

Polycystic ovary syndrome (PCOS) affects 5-20% of women of reproductive age worldwide. The condition is characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology (PCOM) - with excessive androgen production by the ovaries being a key feature of PCOS. Metabolic dysfunction characterized by insulin resistance and compensatory hyperinsulinaemia is evident in the vast majority of affected individuals. PCOS increases the risk for type 2 diabetes mellitus, gestational diabetes and other pregnancy-related complications, venous thromboembolism, cerebrovascular and cardiovascular events and endometrial cancer. PCOS is a diagnosis of exclusion, based primarily on the presence of hyperandrogenism, ovulatory dysfunction and PCOM. Treatment should be tailored to the complaints and needs of the patient and involves targeting metabolic abnormalities through lifestyle changes, medication and potentially surgery for the prevention and management of excess weight, androgen suppression and/or blockade, endometrial protection, reproductive therapy and the detection and treatment of psychological features. This Primer summarizes the current state of knowledge regarding the epidemiology, mechanisms and pathophysiology, diagnosis, screening and prevention, management and future investigational directions of the disorder.

0 comments Cited 367 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Gut microbiota–bile acid–interleukin-22 axis orchestrates polycystic ovary syndrome

Xinyu Qi, Chuyu Yun, Lulu Sun … (2019)

Polycystic ovary syndrome (PCOS) is characterized by androgen excess, ovulatory dysfunction and polycystic ovaries1, and is often accompanied by insulin resistance2. The mechanism of ovulatory dysfunction and insulin resistance in PCOS remains elusive, thus limiting the development of therapeutics. Improved metabolic health is associated with a relatively high microbiota gene content and increased microbial diversity3,4. This study aimed to investigate the impact of the gut microbiota and its metabolites on the regulation of PCOS-associated ovarian dysfunction and insulin resistance. Here, we report that Bacteroides vulgatus was markedly elevated in the gut microbiota of individuals with PCOS, accompanied by reduced glycodeoxycholic acid and tauroursodeoxycholic acid levels. Transplantation of fecal microbiota from women with PCOS or B. vulgatus-colonized recipient mice resulted in increased disruption of ovarian functions, insulin resistance, altered bile acid metabolism, reduced interleukin-22 secretion and infertility. Mechanistically, glycodeoxycholic acid induced intestinal group 3 innate lymphoid cell IL-22 secretion through GATA binding protein 3, and IL-22 in turn improved the PCOS phenotype. This finding is consistent with the reduced levels of IL-22 in individuals with PCOS. This study suggests that modifying the gut microbiota, altering bile acid metabolism and/or increasing IL-22 levels may be of value for the treatment of PCOS.

0 comments Cited 269 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Baoying Liao: URI : https://loop.frontiersin.org/people/1126515

Xinyu Qi: URI : https://loop.frontiersin.org/people/1563194

Jie Qiao: URI : https://loop.frontiersin.org/people/829996

Yanli Pang: URI : https://loop.frontiersin.org/people/1282187

Journal

Journal ID (nlm-ta): Front Endocrinol (Lausanne)

Journal ID (iso-abbrev): Front Endocrinol (Lausanne)

Journal ID (publisher-id): Front. Endocrinol.

Title: Frontiers in Endocrinology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1664-2392

Publication date (Electronic): 14 February 2022

Publication date Collection: 2022

Volume: 13

Electronic Location Identifier: 815968

Affiliations

[1] ¹ Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital , Beijing, China

[2] ² National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital , Beijing, China

[3] ³ Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education , Beijing, China

[4] ⁴ Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Peking University Third Hospital , Beijing, China

[5] ⁵ Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University , Beijing, China

[6] ⁶ Key Laboratory of Molecular Cardiovascular Science, Peking University, Ministry of Education , Beijing, China

Author notes

Edited by: Aylin Carla Hanyaloglu, Imperial College London, United Kingdom

Reviewed by: Lisa Owens, Imperial College London, United Kingdom; Juehua Yu, The First Affiliated Hospital of Kunming Medical University, China; YunFeng Cao, Chinese Academy of Sciences (CAS), China

*Correspondence: Yanli Pang, yanlipang@ 123456bjmu.edu.cn

This article was submitted to Gut Endocrinology, a section of the journal Frontiers in Endocrinology

Article

DOI: 10.3389/fendo.2022.815968

PMC ID: 8883052

PubMed ID: 35237237

SO-VID: 750fa9d4-9552-4254-a89e-c2257794da46

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 16 November 2021

Date accepted : 06 January 2022

Page count

Figures: 6, Tables: 3, Equations: 0, References: 49, Pages: 14, Words: 6862

Funding

Funded by: National Key Research and Development Program of China, doi 10.13039/501100012166;

Award ID: 2018YFC1003200, 2018YFC1003900

Funded by: National Natural Science Foundation of China, doi 10.13039/501100001809;

Effects of Androgen Excess-Related Metabolic Disturbances on Granulosa Cell Function and Follicular Development

Read this article at

Abstract

Related collections

Journal of the ASEAN Federation of Endocrine Societies

Most cited references 49

Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment

Polycystic ovary syndrome.

Gut microbiota–bile acid–interleukin-22 axis orchestrates polycystic ovary syndrome

Author and article information

Contributors

Journal

Affiliations

Author notes

Article

History

Page count

Funding

Categories

Comments

Comment on this article

Similar content 203

Cited by 14

Most referenced authors 685