Abstract

BackgroundA decrease in HOXA11 expression in eutopic mid-secretory endometrium has been found in women with endometriosis-associated infertility.MethodsUsing Real-time quantitative PCR (RQ-PCR) and western blotting analysis we studied the HOXA11 transcript and protein levels in mid-luteal eutopic endometrium from eighteen infertile women with minimal endometriosis, sixteen healthy fertile women and sixteen infertile women with fallopian tubal occlusion from the Polish population. We also evaluated transcript levels of DNA methyltransferases DNMT1, DNMT3A and DNMT3B in these groups of women.ResultsThere were significantly lower levels of HOXA11 transcripts (p = 0.003, p = 0.041) and protein (p = 0.004, p = 0.001) in women with endometriosis as compared to fertile women and infertile women with tubal occlusion. Moreover, we found significantly higher methylation levels of the CpG region in the first exon of HOXA11 in infertile women with endometriosis compared with fertile women (p < 0.001) and infertile women with tubal occlusion (p < 0.001). We also observed significantly increased levels of DNMT3A transcript in women with endometriosis than fertile women (p = 0.044) and infertile women with tubal occlusion (p = 0.047). However, we did not observe significant differences in DNMT1 and DNMT3B transcript levels between these investigated groups of women.ConclusionsWe confirmed that reduced HOXA11 expression may contribute to endometriosis-associated infertility. Moreover, we found that DNA hypermethylation can be one of the possible molecular mechanisms causing a decrease in HOXA11 expression in the eutopic mid-secretory endometrium in infertile women with endometriosis.

Highlights

  • A decrease in HOXA11 expression in eutopic mid-secretory endometrium has been found in women with endometriosis-associated infertility

  • Endometriosis has been recognized as a disease accompanied by aberrant methylation and expression of steroidogenic factor-1 (SF-1), estrogen receptor 2 (ESR2), progesterone receptor (PR-B) and HOXA10 genes in the eutopic endometrium of women with endometriosis [16,17,18,19]

  • Patients and controls Since advanced endometriosis may lead to anatomical distortions and adhesions resulting in infertility, we focused our study on infertility associated with minimal endometriosis

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Summary

Introduction

A decrease in HOXA11 expression in eutopic mid-secretory endometrium has been found in women with endometriosis-associated infertility. Endometriosis lesions can be located in the cavity and walls of the pelvis, on the ovaries, the fallopian tubes, the rectal-vaginal septum, and other body sites [1,2] This disease is often accompanied by pelvic pain, inflammation and results in infertility in 30 to 50% of the affected women [3,4,5]. We studied the effect of DNA regulatory sequences’ methylation on the HOXA11 transcript and protein levels in eighteen infertile women with minimal endometriosis, sixteen fertile women and sixteen infertile women with fallopian tubal occlusion from a Polish cohort. In these groups of women, we evaluated transcript levels of DNA methyltransferases DNMT1, DNMT3A and DNMT3B

Methods
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Conclusion

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