Decreased endometrial HOXA10 expression associated with use of the copper intrauterine device

Abstract

Objective-To characterize human endometrial HOXA10 expression in patients using copper intrauterine devices (IUD).Design-Case-control study. Setting-Academic medical center Patient(s)-Women using copper IUDInterventions(s)-Immunohistochemical analysis of endometrial HOXA10 expression in biopsies obtained from 24 women using copper Paraguard T380A as well as in biopsies obtained from 10 normal cycling women who were not using IUD or hormonal contraceptives. Main Outcome Measure(s)-Endometrial HOXA10 expression.Result(s)-Endometrial HOXA10 expression was markedly decreased in biopsies obtained from women using IUD contraceptive when compared to controls. The mean H score for endometrial stromal cell HOXA10 expression in biopsies obtained from women using Paraguard IUD was 0.21 compared to 2.2 in the control endometrial biopsies (P<0.001). Endometrial glandular expression of HOXA10 was absent in all IUD users. Conclusion(s)-Decreasedendometrial HOXA10 expression was apparent in women who use a copper IUD. Expression of HOXA10 is essential for endometrial receptivity. A novel mechanism of copper IUD action involves suppression of genes required for endometrial receptivity. The dramatic decrease of endometrial HOXA10 in response to IUD use may contribute to contraceptive efficacy.

Reduced expression and concomitant promoter hypermethylation of HOXA10 in endometrium from women wearing intrauterine devices

“…Consistent with published reports (13,25), endometrial HOXA10 expression was localized in the nucleus of glandular epithelial and stromal cells, irrespective of the menstrual phase (Fig. 1).…”

“…As reported by Tetrault et al (13), the HOXA10 expression was significantly lower in the endometrium from IUD users than that from nonusers (P¼.0008). We also found that the lower HOXA10 expression level was associated with longer duration of IUD usage (P¼.003; Fig.…”

“…Stimulation with one proinflammatory cytokine, interleukin (IL)-1b, which is known to be involved in the inflammatory immune response (34), is reported to result in nearly 90% decrease in HOXA10 expression in decidual cells (35). It is thus speculated that the IUD's local foreign body effects may stimulate the production of proinflammatory cytokines, such as IL-1b, leading to decreased endometrial HOXA10 expression (13). Along this line, prolonged IUD usage could result in persistent suppression of HOXA10 expression, which in turn induces HOXA10 promoter hypermethylation, ultimately leading to silencing of its expression.…”

“…Recently, Tetrault et al (13) reported that the use of copper IUD was associated with decreased endometrial HOXA10 expression. They also reported that age and the menstrual phase, but not the duration of IUD usage, were associated with HOXA10 expression.…”

Regulation of tryptophan 2,3-dioxygenase by HOXA10 enhances embryo viability through serotonin signaling

“…There are no known human mutations of the Hoxa10 or Hoxa11 genes; however, women with implantation defects, including endometriosis, polycystic ovarian syndrome, hydrosalpinges, and submucosal myomas, have diminished expression of these genes (9,12,30,37). Endometrium from women using contraception have also shown to have decreased levels of Hoxa10 (41). The associations between altered Hoxa10 expression and implantation defects are clear.…”