Fangfang Wang1, Ningning Xie2, Yan Wu2, Qing Zhang2, Yuhang Zhu2, Minchen Dai2, Jue Zhou3, Jiexue Pan4, Mengling Tang5, Qi Cheng2, Biwei Shi2, Qinyuan Guo6, Xinling Li6, Lifeng Xie6, Bing Wang7, Dongxia Yang8, Qing Weng9, Lanzhong Guo10, Jisheng Ye10, Mingwo Pan11, Shuyi Zhang12, Hua Zhou13, Cailan Zhen14, Ping Liu15, Ke Ning16, Lisa Brackenridge17, Paul J Hardiman17, Fan Qu18. 1. Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China; Institute for Women's Health, University College London, London, United Kingdom. 2. Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China. 3. College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, China; Institute for Women's Health, University College London, London, United Kingdom. 4. First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China. 5. School of Public Health, Zhejiang University, Hangzhou, China. 6. Maternal and Child Healthcare Hospital of Liuzhou, Liuzhou, China. 7. Second Hospital of Jiaxing, Jiaxing, China. 8. Second Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China. 9. First People's Hospital of Yuhang District of Hangzhou, Hangzhou, China. 10. Dongyang Women's and Children's Hospital, Dongyang, China. 11. Guangdong Women and Children Hospital, Guangzhou, China. 12. Baiyin City Maternity and Childcare Hospital, Baiyin, China. 13. Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. 14. People's Hospital of Lucheng, Lucheng, China. 15. Key Laboratory of Birth Defects and Related Diseases of Women and Children of the Ministry of Education, West China Second Hospital, Chengdu, People's Republic of China. 16. Department of Social Science, Institute of Education, University College London, London, United Kingdom. 17. Institute for Women's Health, University College London, London, United Kingdom. 18. Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China; Institute for Women's Health, University College London, London, United Kingdom. Electronic address: syqufan@zju.edu.cn.
Abstract
OBJECTIVE: To explore the association of circadian rhythm disruption with polycystic ovary syndrome (PCOS) and the potential underlying mechanism in ovarian granulosa cells (GCs). DESIGN: Multicenter questionnaire-based survey, in vivo and ex vivo studies. SETTING: Twelve hospitals in China, animal research center, and research laboratory of a women's hospital. PATIENTS/ANIMALS: A total of 436 PCOS case subjects and 715 control subjects were recruited for the survey. In vivo and ex vivo studies were conducted in PCOS-model rats and on ovarian GCs collected from women with PCOS and control subjects. INTERVENTION(S): The PCOS rat model was established with the use of testosterone propionate. MAIN OUTCOME MEASURE(S): Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), RNA sequencing, rhythmicity analysis, functional enrichment analysis. RESULT(S): There was a significant correlation between night shift work and PCOS. PCOS-model rats presented distinct differences in the circadian variation of corticotropin-releasing hormone, adrenocorticotropic hormone, prolactin, and a 4-h phase delay in thyrotropic hormone levels. The motif enrichment analysis of ATAC-seq revealed the absence of clock-related transcription factors in specific peaks of PCOS group, and RNA sequencing ex vivo at various time points over 24 hours demonstrated the differential rhythmic expression patterns of women with PCOS. Kyoto Encyclopedia of Genes and Genomes analysis further highlighted metabolic dysfunction, including both carbohydrate and amino acid metabolism and the tricarboxylic acid cycle. CONCLUSION(S): There is a significant association of night shift work with PCOS, and genome-wide chronodisruption exists in ovarian GCs.
OBJECTIVE: To explore the association of circadian rhythm disruption with polycystic ovary syndrome (PCOS) and the potential underlying mechanism in ovarian granulosa cells (GCs). DESIGN: Multicenter questionnaire-based survey, in vivo and ex vivo studies. SETTING: Twelve hospitals in China, animal research center, and research laboratory of a women's hospital. PATIENTS/ANIMALS: A total of 436 PCOS case subjects and 715 control subjects were recruited for the survey. In vivo and ex vivo studies were conducted in PCOS-model rats and on ovarian GCs collected from women with PCOS and control subjects. INTERVENTION(S): The PCOSrat model was established with the use of testosterone propionate. MAIN OUTCOME MEASURE(S): Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), RNA sequencing, rhythmicity analysis, functional enrichment analysis. RESULT(S): There was a significant correlation between night shift work and PCOS. PCOS-model rats presented distinct differences in the circadian variation of corticotropin-releasing hormone, adrenocorticotropic hormone, prolactin, and a 4-h phase delay in thyrotropic hormone levels. The motif enrichment analysis of ATAC-seq revealed the absence of clock-related transcription factors in specific peaks of PCOS group, and RNA sequencing ex vivo at various time points over 24 hours demonstrated the differential rhythmic expression patterns of women with PCOS. Kyoto Encyclopedia of Genes and Genomes analysis further highlighted metabolic dysfunction, including both carbohydrate and amino acid metabolism and the tricarboxylic acid cycle. CONCLUSION(S): There is a significant association of night shift work with PCOS, and genome-wide chronodisruption exists in ovarian GCs.
Authors: Bradley B Jamieson; Aleisha M Moore; Dayanara B Lohr; Simone X Thomas; Lique M Coolen; Michael N Lehman; Rebecca E Campbell; Richard Piet Journal: Front Endocrinol (Lausanne) Date: 2022-08-05 Impact factor: 6.055