Association between circadian rhythm disruption and polycystic ovary syndrome,Fertility and Sterility

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Association between circadian rhythm disruption and polycystic ovary syndrome
Fertility and Sterility ( IF 6.7 ) Pub Date : 2020-12-01 , DOI: 10.1016/j.fertnstert.2020.08.1425
Fangfang Wang ₁ , Ningning Xie ₂ , Yan Wu ₂ , Qing Zhang ₂ , Yuhang Zhu ₂ , Minchen Dai ₂ , Jue Zhou ₃ , Jiexue Pan ₄ , Mengling Tang ₅ , Qi Cheng ₂ , Biwei Shi ₂ , Qinyuan Guo ₆ , Xinling Li ₆ , Lifeng Xie ₆ , Bing Wang ₇ , Dongxia Yang ₈ , Qing Weng ₉ , Lanzhong Guo ₁₀ , Jisheng Ye ₁₀ , Mingwo Pan ₁₁ , Shuyi Zhang ₁₂ , Hua Zhou ₁₃ , Cailan Zhen ₁₄ , Ping Liu ₁₅ , Ke Ning ₁₆ , Lisa Brackenridge ₁₇ , Paul J Hardiman ₁₇ , Fan Qu ₁

Affiliation

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.
Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, China; Institute for Women's Health, University College London, London, United Kingdom.
First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
School of Public Health, Zhejiang University, Hangzhou, China.
Maternal and Child Healthcare Hospital of Liuzhou, Liuzhou, China.
Second Hospital of Jiaxing, Jiaxing, China.
Second Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China.
First People's Hospital of Yuhang District of Hangzhou, Hangzhou, China.
Dongyang Women's and Children's Hospital, Dongyang, China.
Guangdong Women and Children Hospital, Guangzhou, China.
Baiyin City Maternity and Childcare Hospital, Baiyin, China.
Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
People's Hospital of Lucheng, Lucheng, China.
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.
Department of Social Science, Institute of Education, University College London, London, United Kingdom.
Institute for Women's Health, University College London, London, United Kingdom.

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.

更新日期：2020-12-01

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