Hum. Reprod. Advance Access originally published online on June 24, 2005
Human Reproduction 2005 20(10):2724-2735; doi:10.1093/humrep/dei140
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Reproductive biology |
Chemokine expression is dysregulated in the endometrium of women using progestin-only contraceptives and correlates to elevated recruitment of distinct leukocyte populations
1 Prince Henry’s Institute of Medical Research, PO Box 5152, Clayton, Victoria 3168, 2 Department of Obstetrics & Gynaecology, Monash University, Clayton, Victoria 3168, Australia and 3 Department of Reproductive and Developmental Sciences, University of Edinburgh, Centre for Reproductive Biology, Edinburgh, UK
4 To whom correspondence should be addressed. E-mail: naomi.morison{at}phimr.monash.edu.au
R.L.Jones and N.B.Morison contributed equally to this work
BACKGROUND: Breakthrough bleeding (BTB) is the most common reason for discontinuation of progestin-only (p-only) contraceptives, yet the causes are unknown. Use of p-only contraceptives is associated with elevated influx of endometrial leukocytes, similar to that observed perimenstrually or within decidualized endometrium. We hypothesized that chemokine expression is altered in women using p-only contraceptives, leading to abnormal leukocyte recruitment and BTB. METHODS: Expression of eight highly abundant endometrial chemokines was examined using immunohistochemistry and real-time PCR, in endometria from women using subdermal and intrauterine levonorgestrel and correlated to leukocyte subpopulations. RESULTS: Macrophage-derived chemokine (MDC), hemofiltrate CC chemokine-1 (HCC-1), monocyte chemoattractant protein-3 (MCP-3), interleukin-8 (IL-8) and eotaxin were strongly produced by epithelial glands, comparable to levels in premenstrual phase endometrium. Stromal cells were negative for chemokines in atrophic/shedding endometria, but intensely positive in highly decidualized tissues for MDC, MCP-3, HCC-1 and 6Ckine. Macrophage inflammatory protein-1
(MIP-1b) and HCC-4 were suppressed in all p-exposed endometria. CONCLUSIONS: These data demonstrate that chemokine expression is dysregulated in p-exposed endometria, consistent with the morphological appearance of the endometrium and the leukocyte subsets present. This reinforces a potential role for chemokines in the elevated leukocyte recruitment that contributes to endometrial fragility and BTB.
Key words: chemokines/contraceptives/endometrium/leukocytes/progestin
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