Divergent endometrial inflammatory cytokine expression at peri-implantation period and after the stimulation by copper intrauterine device.

Chia-Hung Chou,Po-Nien Tsao,Chia-Tung Shun,Yu-Shih Yang,Shee-Uan Chen,Jehn-Hsiahn Yang

doi:10.1038/srep15157

Chia-Hung Chou, Po-Nien Tsao + Show 4 more

Open Access

https://doi.org/10.1038/srep15157

Copy DOI

Abstract

Endometrial inflammation has contradictory effects. The one occurring at peri-implantation period is favourable for embryo implantation, whereas the other occurring after the stimulation by copper intrauterine device (Cu-IUD) prevents from embryo implantation. In this study, 8 week female ICR mice were used to investigate the endometrial inflammation, in which they were at proestrus stage (Group 1), at peri-implantation period (Group 2), and had a copper wire implanted into right uterine horn (Group 3). Cytokine array revealed that two cytokines were highly expressed in Group 2 and Group 3 as compared with Group 1, and seven cytokines, including tumour necrosis factor α (TNF-α), had selectively strong expression in Group 3. Immunohistochemistry demonstrated prominent TNF-α staining on the endometrium after Cu-IUD stimulation, and in vitro culture of human endometrial glandular cells with Cu induced TNF-α secretion. The increased TNF-α concentration enhanced in vitro THP-1 cells chemotaxis, and reduced embryo implantation rates. These results suggest that inflammatory cytokine profiles of endometrium are different between those at peri-implantation period and after Cu-IUD stimulation, and TNF-α is the one with selectively strong expression in the latter. It might account for the contradictory biological effects of endometrial inflammation.

Highlights

Copper intrauterine device (Cu-IUD) is one of the most effective forms for birth control and has been used for a couple of decades
For Group 2 mice, intraperitoneal PMSG 5 IU was injected for 2 consecutive days, followed by hCG 10 IU injection, and endometrial tissue was obtained 3.5 days later, roughly at the peri-implantation endometrium
Intense endometrial inflammation occurs thereafter, and embryo implantation is prohibited (Fig. 7). Endometrial inflammation occurs both at peri-implantation period (Group 2) and after the stimulation by Cu-IUD (Group 3), though they have contradictory effects on embryo implantation

Summary

Introduction

Copper intrauterine device (Cu-IUD) is one of the most effective forms for birth control and has been used for a couple of decades. Cu-IUD has been found to alter cytokine and integrin expression in the endometrium, and interferes with embryo implantation[8,9]. It appears that the endometrial inflammation has contradictory results. One is favourable for embryo implantation, as is shown at the peri-implantation period, whereas the other prevents from embryo implantation, as is noted in the case of Cu-IUD stimulation. Inflammation is a biological response of vascular tissues to harmful stimuli, which is mediated by a variety of molecules. It would be of value to study the different cytokine profiles of endometrial inflammation between those at peri-implantation period and after Cu-IUD stimulation. Results obtained after our experiments might provide important information with regard to the factors influencing embryo implantation

Methods

Results

Conclusion