Abnormal Activation of Tryptophan-Kynurenine Pathway in Women With Polycystic Ovary Syndrome
BackgroundWomen with polycystic ovary syndrome (PCOS) suffer from dysfunctional metabolism and studies have reported increased levels of tryptophan in patients with PCOS. However, the changes of downstream metabolites in tryptophan catabolism pathways remain unclear.MethodsThis is a cross-sectional...
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.877807/full |
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| author | Siyu Wang Siyu Wang Siyu Wang Liangshan Mu Liangshan Mu Chunmei Zhang Chunmei Zhang Xiaoyu Long Xiaoyu Long Yurong Zhang Yurong Zhang Yurong Zhang Rong Li Rong Li Rong Li Rong Li Yue Zhao Yue Zhao Yue Zhao Yue Zhao Yue Zhao Jie Qiao Jie Qiao Jie Qiao Jie Qiao Jie Qiao |
| author_facet | Siyu Wang Siyu Wang Siyu Wang Liangshan Mu Liangshan Mu Chunmei Zhang Chunmei Zhang Xiaoyu Long Xiaoyu Long Yurong Zhang Yurong Zhang Yurong Zhang Rong Li Rong Li Rong Li Rong Li Yue Zhao Yue Zhao Yue Zhao Yue Zhao Yue Zhao Jie Qiao Jie Qiao Jie Qiao Jie Qiao Jie Qiao |
| author_sort | Siyu Wang |
| collection | DOAJ |
| description | BackgroundWomen with polycystic ovary syndrome (PCOS) suffer from dysfunctional metabolism and studies have reported increased levels of tryptophan in patients with PCOS. However, the changes of downstream metabolites in tryptophan catabolism pathways remain unclear.MethodsThis is a cross-sectional study that included 200 PCOS patients and 200 control women who were recruited from the Reproductive Medicine Center of Peking University Third Hospital from October 2017 to June 2019. The PCOS patients and the control group were further divided into subtypes of normal weight and overweight/obesity. Fasting blood samples from all subjects were collected on days 2~3 of a natural menstrual cycle or when amenorrhea for over 40 days with follicle diameter not exceeding 10 mm. The plasma levels of tryptophan metabolites were quantitatively determined by the liquid chromatograph mass spectrometer, including tryptophan, serotonin, kynurenine, kynurenic acid, 3-hydroxykynurenine, and quinolinic acid.ResultsThe tryptophan-kynurenine pathway was dysregulated in women with PCOS, along with significantly elevated levels of tryptophan, serotonin, kynurenine, kynurenic acid, and quinolinic acid. Moreover, levels of tryptophan, kynurenine, and kynurenic acid were positively correlated with luteinizing hormone, anti-Müllerian hormone, fasting insulin, HOMA-IR. tryptophan, and kynurenine and quinolinic acid had an obvious association with C-reactive protein levels. Furthermore, logistic regression showed that tryptophan, serotonin, kynurenine, kynurenic acid and quinolinic acid were all associated significantly with the increased risk of PCOS with the adjustment for potential confounding factors. Additionally, tryptophan, kynurenine, and kynurenic acid had good diagnostic performances for PCOS, and their combination exhibited higher sensitivity and specificity to diagnostic efficiency, with the area under the ROC curve of 0.824 (95% CI 0.777-0.871), which was comparable to the endocrine indicators.Conclusion (s)The tryptophan-kynurenine pathway was abnormally activated in PCOS patients. |
| first_indexed | 2024-04-13T22:19:30Z |
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| id | doaj.art-ad8715e2209c4c37902a2265494c9d69 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-13T22:19:30Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-ad8715e2209c4c37902a2265494c9d692022-12-22T02:27:21ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-06-011310.3389/fendo.2022.877807877807Abnormal Activation of Tryptophan-Kynurenine Pathway in Women With Polycystic Ovary SyndromeSiyu Wang0Siyu Wang1Siyu Wang2Liangshan Mu3Liangshan Mu4Chunmei Zhang5Chunmei Zhang6Xiaoyu Long7Xiaoyu Long8Yurong Zhang9Yurong Zhang10Yurong Zhang11Rong Li12Rong Li13Rong Li14Rong Li15Yue Zhao16Yue Zhao17Yue Zhao18Yue Zhao19Yue Zhao20Jie Qiao21Jie Qiao22Jie Qiao23Jie Qiao24Jie Qiao25Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, ChinaKey Laboratory of Assisted Reproduction, Ministry of Education, Beijing, ChinaBeijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, ChinaCenter for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, ChinaNational Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, ChinaCenter for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, ChinaNational Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, ChinaCenter for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, ChinaNational Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, ChinaCenter for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, ChinaKey Laboratory of Assisted Reproduction, Ministry of Education, Beijing, ChinaBeijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, ChinaCenter for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, ChinaKey Laboratory of Assisted Reproduction, Ministry of Education, Beijing, ChinaBeijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, ChinaNational Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, ChinaCenter for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, ChinaKey Laboratory of Assisted Reproduction, Ministry of Education, Beijing, ChinaBeijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, ChinaNational Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, ChinaResearch Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences, Beijing, ChinaCenter for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, ChinaKey Laboratory of Assisted Reproduction, Ministry of Education, Beijing, ChinaBeijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, ChinaNational Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, ChinaResearch Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences, Beijing, ChinaBackgroundWomen with polycystic ovary syndrome (PCOS) suffer from dysfunctional metabolism and studies have reported increased levels of tryptophan in patients with PCOS. However, the changes of downstream metabolites in tryptophan catabolism pathways remain unclear.MethodsThis is a cross-sectional study that included 200 PCOS patients and 200 control women who were recruited from the Reproductive Medicine Center of Peking University Third Hospital from October 2017 to June 2019. The PCOS patients and the control group were further divided into subtypes of normal weight and overweight/obesity. Fasting blood samples from all subjects were collected on days 2~3 of a natural menstrual cycle or when amenorrhea for over 40 days with follicle diameter not exceeding 10 mm. The plasma levels of tryptophan metabolites were quantitatively determined by the liquid chromatograph mass spectrometer, including tryptophan, serotonin, kynurenine, kynurenic acid, 3-hydroxykynurenine, and quinolinic acid.ResultsThe tryptophan-kynurenine pathway was dysregulated in women with PCOS, along with significantly elevated levels of tryptophan, serotonin, kynurenine, kynurenic acid, and quinolinic acid. Moreover, levels of tryptophan, kynurenine, and kynurenic acid were positively correlated with luteinizing hormone, anti-Müllerian hormone, fasting insulin, HOMA-IR. tryptophan, and kynurenine and quinolinic acid had an obvious association with C-reactive protein levels. Furthermore, logistic regression showed that tryptophan, serotonin, kynurenine, kynurenic acid and quinolinic acid were all associated significantly with the increased risk of PCOS with the adjustment for potential confounding factors. Additionally, tryptophan, kynurenine, and kynurenic acid had good diagnostic performances for PCOS, and their combination exhibited higher sensitivity and specificity to diagnostic efficiency, with the area under the ROC curve of 0.824 (95% CI 0.777-0.871), which was comparable to the endocrine indicators.Conclusion (s)The tryptophan-kynurenine pathway was abnormally activated in PCOS patients.https://www.frontiersin.org/articles/10.3389/fendo.2022.877807/fullpolycystic ovary syndrometryptophan metabolismkynureninekynurenic acidobesity |
| spellingShingle | Siyu Wang Siyu Wang Siyu Wang Liangshan Mu Liangshan Mu Chunmei Zhang Chunmei Zhang Xiaoyu Long Xiaoyu Long Yurong Zhang Yurong Zhang Yurong Zhang Rong Li Rong Li Rong Li Rong Li Yue Zhao Yue Zhao Yue Zhao Yue Zhao Yue Zhao Jie Qiao Jie Qiao Jie Qiao Jie Qiao Jie Qiao Abnormal Activation of Tryptophan-Kynurenine Pathway in Women With Polycystic Ovary Syndrome Frontiers in Endocrinology polycystic ovary syndrome tryptophan metabolism kynurenine kynurenic acid obesity |
| title | Abnormal Activation of Tryptophan-Kynurenine Pathway in Women With Polycystic Ovary Syndrome |
| title_full | Abnormal Activation of Tryptophan-Kynurenine Pathway in Women With Polycystic Ovary Syndrome |
| title_fullStr | Abnormal Activation of Tryptophan-Kynurenine Pathway in Women With Polycystic Ovary Syndrome |
| title_full_unstemmed | Abnormal Activation of Tryptophan-Kynurenine Pathway in Women With Polycystic Ovary Syndrome |
| title_short | Abnormal Activation of Tryptophan-Kynurenine Pathway in Women With Polycystic Ovary Syndrome |
| title_sort | abnormal activation of tryptophan kynurenine pathway in women with polycystic ovary syndrome |
| topic | polycystic ovary syndrome tryptophan metabolism kynurenine kynurenic acid obesity |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.877807/full |
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