Induction of endometriosis alters the peripheral and endometrial regulatory T cell population in the non-human primate

A. Braundmeier, K. Jackson, J. Hastings, J. Koehler, R. Nowak, A. Fazleabas

Research output: Contribution to journalArticlepeer-review


Background: Endometriosis is a gynecological condition that is characterized by extreme abdominal pain and also decreased fertility. Regulatory T cells (Tregs) have immunosuppressive activity critical for embryonic implantation and likewise the acceptance of tissue engraftment. Utilizing the induced non-human primate (Papio anubis) model of endometriosis, we hypothesize that endometriosis decreases the peripheral and endomet rial Treg profile, whereas ectopic lesions have increased Treg localization. Methods Peripheral blood and endometrium were obtained throughout the menstrual cycle prior to and after induction of disease. Animals were randomly assigned to control (n 7) or diseased (n 16) treatment groups. Endometriosis was induced by i.p. injection of autologous menstrual tissue for 2 consecutive months during menses. Peripheral blood and endometrial tissue were collected at d9-11PO at 1, 3, 6, 9, 12 and 15 months post-induction of disease for fluorescence-activated cell sorting, quantitative RTPCR and immunohistochemistry. Ectopic lesions were excised at 1 and 6 months post-inoculation and also harvested at necropsy (15 months) and processed for RNA of IHC. Identification of Tregs through analysis of FOXP3 expression was conducted utlilizing several methodologies. Differences were determined by non-parametric statistical analysis between all treatment groups and time points. Results In control animals, the proportion of peripheral natural Tregs (nTregs) was reduced (P < 0.05) during the mid-and late secretory stages of the menstrual cycle compared with menses. The induction of disease decreased peripheral Treg expression at early time points (P < 0.05) and this remained low throughout the time course, compared with the pre-inoculatory level of an individual. FOXP3 gene expression and Treg populations were also decreased in the eutopic endometrium (P < 0.05) compared with control animals, whereas these parameters were increased in ectopic lesions (P < 0.05), compared with the eutopic endometrium. Conclusions Our data suggest that a reduction in peripheral Tregs may be a causative factor for endometriosis-associated infertility, while the increase in ectopic Treg expression may aid lesion development. Furthermore, endometriosis appears to disrupt Treg recruitment in both eutopic and ectopic endometrium.

Original languageEnglish (US)
Pages (from-to)1712-1722
Number of pages11
JournalHuman Reproduction
Issue number6
StatePublished - Jun 2012


  • Endometriosis
  • Fertility
  • Pathogenesis
  • Primate
  • Regulatory T cells

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology


Dive into the research topics of 'Induction of endometriosis alters the peripheral and endometrial regulatory T cell population in the non-human primate'. Together they form a unique fingerprint.

Cite this