Endometrial expression of epithelial neutrophil-activating peptide-78 during the menstrual cycle or in progestin-only contraceptive users with breakthrough bleeding and the influence of doxycycline therapy
Endometrial expression of epithelial neutrophil-activating peptide-78 during the menstrual cycle or in progestin-only contraceptive users with breakthrough bleeding and the influence of doxycycline therapy
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DOI：
10.1093/humrep/del398
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发表时间：
2007-02-01
影响因子：
6.1
通讯作者：
Archer, D. F.
中科院分区：
文献类型：
--
作者：
Chegini, N.;Luo, X.;Archer, D. F.
背景技术背景：子宫内膜突破性出血的特征在于炎症反应和促炎介质的产生增加，其中之一可能是上皮细胞嗜中性粒细胞活化肽-78（ENA-78），一种具有嗜中性粒细胞活化特性的趋化因子。方法和结果：因此，我们研究了子宫内膜ENA-78的表达Norplant用户作为孕激素避孕与各种出血模式（n = 35）相比，非用户与正常月经周期（n = 55）。ENA-78在子宫内膜间质细胞（ESCs）中的表达主要集中在分泌期。与月经规律者和闭经者相比，不规则出血者的ENA-78表达增加。25例使用Norplant 3-6个月后，子宫冲洗液和血清中ENA-78水平较用药前明显升高（P < 0.05）。与基线相比，这些水平在接受多西环素（Dox）治疗（25 mg/每日两次，持续6个月）的Norplant使用者中没有显著变化，当在研究中途或研究结束时测量时（n = 25）。醋酸甲羟孕酮（MPA）和肿瘤坏死因子-α治疗（TNF-α）（25 ng/ml），而不是17 β-雌二醇（E-2）或E-2 + MPA（10（-8）M），分别代表暴露于避孕和炎症条件的子宫内膜，增加了ESC产生ENA-78的水平，而与Dox（25 μ g/ml）共处理则降低了这一点（P < 0.05）。结论：ENA-78的子宫内膜产生在经历突破性出血的仅孕激素避孕药使用者中发生改变，并且在ESC中受到MPA和TNF-α的调节。虽然Dox治疗没有改变子宫ENA-78分泌，但其在ESCs中的抑制表明Dox通过抗炎机制作用于特定部位，可能会影响避孕药使用者突破性出血的结果。
BACKGROUND: Endometrial breakthrough bleeding is characterized by an inflammatory reaction and increased production of proinflammatory mediators, one of which may be epithelial neutrophil-activating peptide-78 (ENA-78), a chemokine with neutrophil-activating properties. METHODS AND RESULTS: We therefore investigated the endometrial expression of ENA-78 in Norplant users as progestin-only contraceptive with various bleeding patterns (n = 35) as compared with non-users with a normal menstrual cycle (n = 55). The endometrial stromal cells (ESCs) were the major site of ENA-78 expression with the highest levels found during the secretory phase. The expression of ENA-78 was increased in Norplant users with irregular bleeding as compared with those with regular cycles and amenorrhoea. The levels of ENA-78 detected in uterine washes and sera after the use of Norplant for 3-6 months (n = 25) increased compared with baseline (P < 0.05). These levels did not significantly change in Norplant users who received doxycycline (Dox) therapy (25 mg/twice daily for 6 months) when measured midway through or at the conclusion of study when compared with the baseline (n = 25). Treatments with medroxyprogesterone acetate (MPA) and tumour necrosis factor-alpha (TNF-alpha) (25 ng/ml), but not 17 beta-estradiol (E-2) or E-2 + MPA (10(-8) M), representing endometrium exposed to contraceptive and inflammatory conditions, respectively, increased the levels of ENA-78 production by ESCs, and this was reduced by co-treatments with Dox (25 mu g/ml) (P < 0.05). CONCLUSIONS: The endometrial production of ENA-78 is altered in progestin-only contraceptive users experiencing breakthrough bleeding and is regulated by MPA and TNF-alpha in ESCs. Although Dox therapy did not alter uterine ENA-78 secretion, its suppression in ESCs suggests that Dox, acting site-specifically and through an anti-inflammatory mechanism, may influence the outcome of breakthrough bleeding in contraceptive users.