ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015
The clock protein period 2 synchronizes mitotic expansion and decidual transformation of human endometrial stromal cells.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 47 citations in OpenAlex.
- BMAL1 Dysregulation as a Contributing Mechanism Linking Obesity to Oocyte and Endometrial Dysfunction in IVF.International journal of molecular sciences · 2026Review
- Research progress and future directions in circadian rhythms for uterine‑related diseases (Review).Molecular medicine reports · 2026Review
- Dysfunctional decidual CD2Frontiers in immunology · 2026Article
- BMAL1 Regulates Collagen Production in the Myometrium and Leiomyomas.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Identification of key genes associated with infertile endometriosis based on bioinformatic analysis.Frontiers in genetics · 2025Article
- Role of circadian clock in female embryo implantation.Frontiers in cell and developmental biology · 2025Review
- Circadian Regulation of Lipid Metabolism during Pregnancy.International journal of molecular sciences · 2024Review
- Gene Regulatory Network Analysis of Decidual Stromal Cells and Natural Killer Cells.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
- The Circadian Clock, Nutritional Signals and Reproduction: A Close Relationship.International journal of molecular sciences · 2023Review
- Latest advances in the study of non-coding RNA-mediated circadian rhythm disorders causing endometrial cancer.Frontiers in oncology · 2023Review
- EndoTime: non-categorical timing estimates for luteal endometrium.Human reproduction (Oxford, England) · 2022Article
- Melatonin and Myo-Inositol: Supporting Reproduction from the Oocyte to Birth.International journal of molecular sciences · 2021Review
- In Silico, In Vitro, and In Vivo Analysis Identifies Endometrial Circadian Clock Genes in Recurrent Implantation Failure.The Journal of clinical endocrinology and metabolism · 2021Article
- The Role of Decidual Subpopulations in Implantation, Menstruation and Miscarriage.Frontiers in reproductive health · 2021Review
- Associated analysis of PER1/TUBB2B with endometrial cancer development caused by circadian rhythm disorders.Medical oncology (Northwood, London, England) · 2020Article
- Curcumin and Endometriosis.International journal of molecular sciences · 2020Review
- Melatonin Promotes Uterine and Placental Health: Potential Molecular Mechanisms.International journal of molecular sciences · 2019Review
- Resveratrol inhibits decidualization by accelerating downregulation of the CRABP2-RAR pathway in differentiating human endometrial stromal cells.Cell death & disease · 2019Article
- Identification of Gene Expression Changes Associated With Uterine Receptivity in Mice.Frontiers in physiology · 2019Article
- Reprogramming of the retinoic acid pathway in decidualizing human endometrial stromal cells.PloS one · 2017Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Implantation requires coordinated interactions between the conceptus and surrounding decidual cells, but the involvement of clock genes in this process is incompletely understood. Circadian oscillations are predicated on transcriptional-translational feedback loops, which balance the activities of the transcriptional activators CLOCK (circadian locomotor output cycles kaput) and brain muscle arnt-like 1 and repressors encoded by PER (Period) and Cryptochrome genes. We show that loss of PER2 expression silences circadian oscillations in decidualizing human endometrial stromal cells (HESCs). Down-regulation occurred between 12 and 24 hours following differentiation and coincided with reduced CLOCK binding to a noncanonical E-box enhancer in the PER2 promoter. RNA sequencing revealed that premature inhibition of PER2 by small interfering RNA knockdown leads to a grossly disorganized decidual response. Gene ontology analysis highlighted a preponderance of cell cycle regulators among the 1121 genes perturbed upon PER2 knockdown. Congruently, PER2 inhibition abrogated mitotic expansion of differentiating HESCs by inducing cell cycle block at G2/M. Analysis of 70 midluteal endometrial biopsies revealed an inverse correlation between PER2 transcript levels and the number of miscarriages in women suffering reproductive failure (Spearman rank test, ρ = -0.3260; P = 0.0046). Thus, PER2 synchronizes endometrial proliferation with initiation of aperiodic decidual gene expression; uncoupling of these events may cause recurrent pregnancy loss.
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Registered trials
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