Altered cytokine gene expression in peripheral blood monocytes across the menstrual cycle in primary dysmenorrhea: a case-control study

PLoS One. 2013;8(2):e55200. doi: 10.1371/journal.pone.0055200. Epub 2013 Feb 4.


Primary dysmenorrhea is one of the most common gynecological complaints in young women, but potential peripheral immunologic features underlying this condition remain undefined. In this paper, we compared 84 common cytokine gene expression profiles of peripheral blood mononuclear cells (PBMCs) from six primary dysmenorrheic young women and three unaffected controls on the seventh day before (secretory phase), and the first (menstrual phase) and the fifth (regenerative phase) days of menstruation, using a real-time PCR array assay combined with pattern recognition and gene function annotation methods. Comparisons between dysmenorrhea and normal control groups identified 11 (nine increased and two decreased), 14 (five increased and nine decreased), and 15 (seven increased and eight decreased) genes with ≥ 2-fold difference in expression (P<0.05) in the three phases of menstruation, respectively. In the menstrual phase, genes encoding pro-inflammatory cytokines (IL1B, TNF, IL6, and IL8) were up-regulated, and genes encoding TGF-β superfamily members (BMP4, BMP6, GDF5, GDF11, LEFTY2, NODAL, and MSTN) were down-regulated. Functional annotation revealed an excessive inflammatory response and insufficient TGF-β superfamily member signals with anti-inflammatory consequences, which may directly contribute to menstrual pain. In the secretory and regenerative phases, increased expression of pro-inflammatory cytokines and decreased expression of growth factors were also observed. These factors may be involved in the regulation of decidualization, endometrium breakdown and repair, and indirectly exacerbate primary dysmenorrhea. This first study of cytokine gene expression profiles in PBMCs from young primary dysmenorrheic women demonstrates a shift in the balance between expression patterns of pro-inflammatory cytokines and TGF-β superfamily members across the whole menstrual cycle, underlying the peripheral immunologic features of primary dysmenorrhea.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Cytokines / classification
  • Cytokines / genetics*
  • Cytokines / immunology
  • Dysmenorrhea / genetics*
  • Dysmenorrhea / immunology
  • Dysmenorrhea / pathology
  • Endometrium / immunology
  • Endometrium / metabolism
  • Endometrium / pathology
  • Female
  • Gene Expression / immunology*
  • Gene Expression Profiling
  • Humans
  • Intercellular Signaling Peptides and Proteins / classification
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / immunology
  • Menstrual Cycle / genetics*
  • Menstrual Cycle / immunology
  • Monocytes / immunology*
  • Monocytes / pathology
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction
  • Young Adult


  • Cytokines
  • Intercellular Signaling Peptides and Proteins

Grant support

This work was supported by the Open Project Program of Traditional Chinese Medicine Department of Nanjing University of Chinese Medicine (YS2012ZYX311), a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institution (PAPD), the National Natural Science Fund of China (81274199, 81073121) and the National Science Fund for Distinguished Young Scholars (81102762), and National Basic Research Program of China (973 Program) (2011CB505300, 2011CB505303). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.