Paired-box gene 2 is down-regulated in endometriosis and correlates with low epidermal growth factor receptor expression

A. A. de Graaff, B. Delvoux, K. K. Van de Vijver, C. M. Kyama, T. M. D'Hooghe, G. A. J. Dunselman, A. Romano*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Paired-box 2 (Pax2) is involved in the development of the female genital tract and has been associated with endometrial pathologies. The expression of Pax2 is induced by epidermal growth factor (EGF) and estrogens. In the present study, Pax2 expression and regulation were investigated in endometriosis. Pax2 protein expression was assessed by immunohistochemistry in the eutopic (i.e. inside the uterus) and ectopic tissue (endometriosis) from 11 patients. Immunoreactivity was high in the endometrium, with strong epithelial and weaker stromal staining. Similar expression patterns of Pax2 were observed in the endometrium of women without endometriosis (n 12). The mRNA level of Pax2 was assessed by real-time PCR in the eutopic and ectopic endometria of 14 patients and in the endometrium from women without endometriosis (n 20). Pax2 expression was lower in endometriotic lesions than that in the eutopic endometrium of patients (P 0.001) and controls (P 0.007). Three possible mechanisms determining low Pax2 expression were investigated: EGF signalling, CpG DNA methylation of the Pax2 promoter and steroid response. The mRNA level of the EGF receptor (EGFR1) was assessed in the samples used for Pax2 mRNA assessment. A significant correlation between EGFR1 and Pax2 in both eutopic and ectopic tissues was observed (R 0.58; slope regression line, 0.81; 95 CI: 0.091.52 and R 0.54; slope regression line, 2.51; 95 CI: 0.024.99, respectively). CpG DNA methylation was analyzed by methyl-specific PCR in two regions of the Pax2 promoter but they were unmethylated in all samples. Steroid responsiveness was assessed using endometrial explant cultures and Pax2 was not regulated by either 17-estradiol or progesterone. In endometriosis patients, Pax2 is down-regulated in the lesions compared with the eutopic tissue, possibly due to low EGF signalling.
Original languageEnglish
Pages (from-to)1676-1684
JournalHuman Reproduction
Issue number6
Publication statusPublished - Jun 2012


  • paired-box 2
  • endometriosis
  • epidermal growth factor
  • CpG methylation
  • estrogen
  • progesterone


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