ArticleEndocrine2016
Effects of BMAL1-SIRT1-positive cycle on estrogen synthesis in human ovarian granulosa cells: an implicative role of BMAL1 in PCOS.
Article in Endocrine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Exploring the potential association and experimental validation of disrupted circadian rhythms with polycystic ovary syndrome via meta-analysis and bioinformatics: a possible pathogenic mechanism.Frontiers in endocrinology · 2025Pooled it
- BMAL1 Dysregulation as a Contributing Mechanism Linking Obesity to Oocyte and Endometrial Dysfunction in IVF.International journal of molecular sciences · 2026Review
- PER3 expression in granulosa cells of women with polycystic ovary syndrome: a potential role of the ovarian peripheral clock in infertility.Molecular biology reports · 2026Article
- The interplay between circadian rhythm components and apoptosis in health and disease.Human cell · 2026Review
- Follicular development impairment in polyendocrine metabolic ovarian syndrome: multidimensional pathophysiological networks and frontier therapeutic targets.Frontiers in immunology · 2026Review
- Sleep Disruption and Shift Work Associate with Increased Risk of Reproductive Endocrine Disorders: Evidence from UK Biobank and Mendelian Randomization.International journal of women's health · 2026Article
- Gut microbiota-derived butyrate and the SIRT1/FoxO1 axis: epigenetic-metabolic regulation of ovarian function in premature ovarian insufficiency-a comprehensive review.Frontiers in microbiology · 2026Review
- BMAL1 attenuates intervertebral disc degeneration by activating the SIRT1/PGC-1α pathway: evidence from vitro studies.Scientific reports · 2025Article
- BMAL1 improves assisted reproductive technology outcomes in patients with polycystic ovary syndrome by targeting BMP6 and regulating ovarian granulosa cell apoptosis.Journal of assisted reproduction and genetics · 2025Article
- Regulation of SIRT1 in Ovarian Function: PCOS Treatment.Current issues in molecular biology · 2023Review
- Synthesis, Regulatory Factors, and Signaling Pathways of Estrogen in the Ovary.Reproductive sciences (Thousand Oaks, Calif.) · 2023Review
- Novel Role of the SIRT1 in Endocrine and Metabolic Diseases.International journal of biological sciences · 2023Review
- Reshaping the Gut Microbiota Through Lifestyle Interventions in Women with PCOS: A Review.Indian journal of microbiology · 2022Review
- The Differential Metabolomes in Cumulus and Mural Granulosa Cells from Human Preovulatory Follicles.Reproductive sciences (Thousand Oaks, Calif.) · 2022Article
- Dysregulated sphingolipid metabolism and autophagy in granulosa cells of women with endometriosis.Frontiers in endocrinology · 2022Article
- Critical Roles of the Circadian Transcription FactorFrontiers in endocrinology · 2022Review
- Melatonin, Clock Genes, and Mammalian Reproduction: What Is the Link?International journal of molecular sciences · 2021Review
- Expression of cell proliferation regulatory factors bricd5, tnfrsf21, cdk1 correlates with expression of clock gene cry1 in testes of Hu rams during puberty.Molecular biology reports · 2021Article
- Autophagy in ovary and polycystic ovary syndrome: role, dispute and future perspective.Autophagy · 2021Review
- Cross-species physiological interactions of endocrine disrupting chemicals with the circadian clock.General and comparative endocrinology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brain and muscle ARNT-like protein 1 (BMAL1) is necessary for fertility and has been found to be essential to follicle growth and steroidogenesis. Sirtuin1 (SIRT1) has been reported to interact with BMAL1 and function in a circadian manner. Evidence has shown that SIRT1 regulates aromatase expression in estrogen-producing cells. We aimed to ascertain if there is a relationship between polycystic ovary syndrome (PCOS) and BMAL1, and whether and how BMAL1 takes part in estrogen synthesis in human granulosa cells (hGCs). Twenty-four women diagnosed with PCOS and 24 healthy individuals undergoing assisted reproduction were studied. BMAL1 expression in their granulosa cells (GCs) was observed by quantitative real-time polymerase chain reaction (qRT-PCR). The level of expression in the PCOS group was lower than that of the group without PCOS (p < 0.05). We also analyzed estrogen synthesis and aromatase expression in KGN cell lines. Both were downregulated after BMAL1 and SIRT1 knock-down and, conversely, upregulated after overexpression treatments of these two genes in KGN cells. Both BMAL1 and SIRT1 had a mutually positive regulation, as did the phosphorylation of JNK. Furthermore, JNK overexpression increased estrogen synthesis activity and the expression levels of aromatase, BMAL1, and SIRT1. In KGN and hGCs, estrogen synthesis and aromatase expression were downregulated after treatment with JNK and SIRT1 inhibitors. In addition, BMAL1, SIRT1, and JNK expression levels were all downregulated. Our results demonstrate the effects of BMAL1 on estrogen synthesis in hGCs and suggest a BMAL1-SIRT1-JNK positive feedback cycle in this process, which points out an important role of BMAL1 in the development of PCOS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.