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  • Title: Chemokine expression is dysregulated in the endometrium of women using progestin-only contraceptives and correlates to elevated recruitment of distinct leukocyte populations.
    Author: Jones RL, Morison NB, Hannan NJ, Critchley HO, Salamonsen LA.
    Journal: Hum Reprod; 2005 Oct; 20(10):2724-35. PubMed ID: 15979999.
    Abstract:
    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-1beta (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.
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