Metabolic dysregulation and gut dysbiosis linked to hyperandrogenism in female mice
Abstract Introduction Polycystic ovary syndrome (PCOS) is a common endocrine pathology in women. In addition to infertility, women with PCOS have metabolic dysregulation which predisposes them to Type 2 diabetes, cardiovascular disease and non‐alcoholic fatty liver disease. Moreover, women with PCOS...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-01-01
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| Series: | Endocrinology, Diabetes & Metabolism |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/edm2.443 |
| _version_ | 1827374784864845824 |
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| author | Annie Chen Alex Handzel Lillian Sau Laura Cui Scott T. Kelley Varykina G. Thackray |
| author_facet | Annie Chen Alex Handzel Lillian Sau Laura Cui Scott T. Kelley Varykina G. Thackray |
| author_sort | Annie Chen |
| collection | DOAJ |
| description | Abstract Introduction Polycystic ovary syndrome (PCOS) is a common endocrine pathology in women. In addition to infertility, women with PCOS have metabolic dysregulation which predisposes them to Type 2 diabetes, cardiovascular disease and non‐alcoholic fatty liver disease. Moreover, women with PCOS have changes in their gut microbial community that may be indicative of dysbiosis. While hyperandrogenism is associated with both the development of metabolic dysfunction and gut dysbiosis in females, the mechanisms involved are not well understood. Methods We used dihydrotestosterone (DHT) and ovariectomy (OVX) mouse models coupled with metabolic assessments and 16S rRNA gene sequencing to explore the contributions of hyperandrogenism and oestrogen deficiency to the development of insulin resistance and gut microbial dysbiosis in pubertal female mice. Results We demonstrated that, while DHT treatment or OVX alone were insufficient to induce insulin resistance during the pubertal‐to‐adult transition, combining OVX with DHT resulted in insulin resistance similar to that observed in letrozole‐treated mice with elevated testosterone and decreased oestrogen levels. In addition, our results showed that OVX and DHT in combination resulted in a distinct shift in the gut microbiome compared to DHT or OVX alone, suggesting that the substantial metabolic dysregulation occurring in the OVX + DHT model was accompanied by unique changes in the abundances of gut bacteria including S24‐7, Rikenellaceae and Mucispirillum schaedleri. Conclusions While hyperandrogenism plays an important role in the development of metabolic dysregulation in female mice, our results indicate that investigation into additional factors influencing insulin resistance and the gut microbiome during the pubertal‐to‐adult transition could provide additional insight into the pathophysiology of PCOS. |
| first_indexed | 2024-03-08T11:40:01Z |
| format | Article |
| id | doaj.art-0381598178c441e6b5e7e99b53a4e1ce |
| institution | Directory Open Access Journal |
| issn | 2398-9238 |
| language | English |
| last_indexed | 2024-03-08T11:40:01Z |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Endocrinology, Diabetes & Metabolism |
| spelling | doaj.art-0381598178c441e6b5e7e99b53a4e1ce2024-01-25T06:48:36ZengWileyEndocrinology, Diabetes & Metabolism2398-92382024-01-0171n/an/a10.1002/edm2.443Metabolic dysregulation and gut dysbiosis linked to hyperandrogenism in female miceAnnie Chen0Alex Handzel1Lillian Sau2Laura Cui3Scott T. Kelley4Varykina G. Thackray5Department of Obstetrics, Gynecology and Reproductive Sciences University of California San Diego, La Jolla California USABioinformatics and Medical Informatics Program San Diego State University San Diego California USADepartment of Obstetrics, Gynecology and Reproductive Sciences University of California San Diego, La Jolla California USADepartment of Obstetrics, Gynecology and Reproductive Sciences University of California San Diego, La Jolla California USABioinformatics and Medical Informatics Program San Diego State University San Diego California USADepartment of Obstetrics, Gynecology and Reproductive Sciences University of California San Diego, La Jolla California USAAbstract Introduction Polycystic ovary syndrome (PCOS) is a common endocrine pathology in women. In addition to infertility, women with PCOS have metabolic dysregulation which predisposes them to Type 2 diabetes, cardiovascular disease and non‐alcoholic fatty liver disease. Moreover, women with PCOS have changes in their gut microbial community that may be indicative of dysbiosis. While hyperandrogenism is associated with both the development of metabolic dysfunction and gut dysbiosis in females, the mechanisms involved are not well understood. Methods We used dihydrotestosterone (DHT) and ovariectomy (OVX) mouse models coupled with metabolic assessments and 16S rRNA gene sequencing to explore the contributions of hyperandrogenism and oestrogen deficiency to the development of insulin resistance and gut microbial dysbiosis in pubertal female mice. Results We demonstrated that, while DHT treatment or OVX alone were insufficient to induce insulin resistance during the pubertal‐to‐adult transition, combining OVX with DHT resulted in insulin resistance similar to that observed in letrozole‐treated mice with elevated testosterone and decreased oestrogen levels. In addition, our results showed that OVX and DHT in combination resulted in a distinct shift in the gut microbiome compared to DHT or OVX alone, suggesting that the substantial metabolic dysregulation occurring in the OVX + DHT model was accompanied by unique changes in the abundances of gut bacteria including S24‐7, Rikenellaceae and Mucispirillum schaedleri. Conclusions While hyperandrogenism plays an important role in the development of metabolic dysregulation in female mice, our results indicate that investigation into additional factors influencing insulin resistance and the gut microbiome during the pubertal‐to‐adult transition could provide additional insight into the pathophysiology of PCOS.https://doi.org/10.1002/edm2.443androgengut microbiomeinsulin resistance |
| spellingShingle | Annie Chen Alex Handzel Lillian Sau Laura Cui Scott T. Kelley Varykina G. Thackray Metabolic dysregulation and gut dysbiosis linked to hyperandrogenism in female mice Endocrinology, Diabetes & Metabolism androgen gut microbiome insulin resistance |
| title | Metabolic dysregulation and gut dysbiosis linked to hyperandrogenism in female mice |
| title_full | Metabolic dysregulation and gut dysbiosis linked to hyperandrogenism in female mice |
| title_fullStr | Metabolic dysregulation and gut dysbiosis linked to hyperandrogenism in female mice |
| title_full_unstemmed | Metabolic dysregulation and gut dysbiosis linked to hyperandrogenism in female mice |
| title_short | Metabolic dysregulation and gut dysbiosis linked to hyperandrogenism in female mice |
| title_sort | metabolic dysregulation and gut dysbiosis linked to hyperandrogenism in female mice |
| topic | androgen gut microbiome insulin resistance |
| url | https://doi.org/10.1002/edm2.443 |
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