Search

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.

Background: This study explored the mechanisms underlying altered neurobehavioural development of female offspring born to mothers with polycystic ovary syndrome (PCOS). Methods: In total, 20 women with PCOS and 32 healthy women who underwent caesarean deliveries with a single female foetus were recruited. Infants were assessed with Dubowitz scoring. Swan71 cell line with stable FOS overexpression was used to verify the regulatory effects of FOS on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) expression. Learning and memory in female first-generation (F1) and second-generation (F2) offspring in a rat model of PCOS was tested using the Morris water maze at puberty and adulthood. Transcriptome analysis of pubertal hippocampi and hypothalami of female F1 offspring was conducted. Findings: Total score and behaviour subscales of Dubowitz scoring were significantly lower in female infants of women with PCOS. FOS and NGF protein levels were downregulated in placental villi of the PCOS group. FOS played a key role in BDNF inhibition and enhancing NGF in Swan71 cells. PCOS female F1 rats exhibited lower target crossing times during puberty when compared to controls. Transcriptome analysis revealed significant changes in hippocampal and hypothalamic neuronal pathways in female F1 rats at puberty. Interpretation: FOS regulation of neurotrophins in the placenta negatively affects neurobehavioural development of female offspring of PCOS mothers. Funding: This study was funded by the National Key R&D Program of China (2018YFC1004900 to F.Q. and F.W.) and the National Natural Science Foundation of China (81874480 to F.Q.; 81873837 to F.W.).

The present systematic review is designed to summarize the evidence concerning the effect of acupuncture on pregnancy outcomes in vitro fertilization with embryo transfer (IVF-ET). We searched MEDLINE, the Wanfang Database, the China Academic Journal Electronic Full-text Database in the China National Knowledge Infrastructure, and the Index to Chinese Periodical Literature. Randomized controlled trials with intervention groups using acupuncture and control groups consisting of no acupuncture or sham (placebo) acupuncture in IVF-ET treatment were selected. Study characteristics were examined from these studies and an intention-to-treat approach was used to extract outcome data from each study. In total, 31 articles including 4450 women passed our selection criteria. The legitimacy, characteristics, and IVF outcomes of the included trials were summarized. Additional Traditional Chinese Medicine (TCM) theory-based, standardized, large-size, randomized, and multicenter trials are necessary prior to any conclusions being drawn on whether TCM can improve IVF outcomes.