Ulipristal acetate resembles mifepristone in modulating human Fallopian tube function
Ulipristal acetate resembles mifepristone in modulating human Fallopian tube function
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DOI：
10.1093/humrep/deu210
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发表时间：
2014-10-01
影响因子：
6.1
通讯作者：
Ho, Pak-Chung
中科院分区：
文献类型：
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作者：
Li, Hang Wun Raymond;Liao, Su-Bin;Ho, Pak-Chung
研究问题：醋酸乌利司他 (UPA) 和米非司酮对人类输卵管中的纤毛搏动频率和肌肉收缩有影响吗？总结答案：UPA 与米非司酮类似，可能通过对输卵管黄体酮受体的激动作用来抑制人类输卵管的纤毛搏动和肌肉收缩。已知的情况：UPA，与米非司酮一样，主要通过抑制排卵作为紧急避孕药。关于其对输卵管功能的影响知之甚少。研究设计、大小、持续时间：这是一项体外实验研究，使用从 11 名因良性非输卵管妇科疾病而接受子宫切除术的女性身上收集的输卵管样本。参与者/材料、设置、方法：分离、培养输卵管上皮和纵向平滑肌纤维，并用 UPA 以 0、20、20 级浓度进行处理。 200 和 2000 ng/ml，以及分级浓度分别为 0、300、3000 和 30 000 ng/ml 的米非司酮。治疗后，使用光度法测定纤毛跳动频率。通过力传感器记录肌肉收缩的基础张力、幅度和频率。通过实时定量PCR测定黄体酮受体（总亚型和PR-B亚型）、甘肽素和肾上腺髓质素的mRNA表达。 主要结果和机会的作用：用所有浓度的UPA和3000 ng/ml或以上的米非司酮治疗后，对纤毛搏动频率有总体剂量依赖性抑制作用（P < 0.0001）。 200 ng/ml或以上UPA和3000 ng/ml或以上米非司酮治疗后，肌肉收缩的基础张力、幅度和频率均显着降低（P < 0.05）。 200 ng/ml 或以上的 UPA 治疗可显着上调输卵管组织中黄体酮受体和甘肽素的 mRNA 表达，并下调肾上腺髓质素的 mRNA 表达（P < 0.05）。 局限性、注意原因：输卵管效应是否可能转化为体内避孕作用的其他机制尚不确定。 研究结果的更广泛意义： 临床相关性UPA 在避孕活动方面的观点值得进一步探索。 研究资助/竞争利益：该研究得到了香港大学医学院生殖、发育和生长中心种子基金的支持。所有作者都没有需要声明的竞争利益。
STUDY QUESTION: Do ulipristal acetate (UPA) and mifepristone have an effect on ciliary beat frequency and muscular contractions in the human Fallopian tube?SUMMARY ANSWER: UPA, in resemblance to mifepristone, inhibits ciliary beat and muscular contraction of the human Fallopian tube, probably through an agonistic effect on the tubal progesterone receptor.WHAT IS KNOWN ALREADY: UPA, like mifepristone, acts as an emergency contraceptive mainly by inhibiting ovulation. Little is known about its effects on tubal function.STUDY DESIGN, SIZE, DURATION: This was an in vitro experimental study using Fallopian tube samples collected from 11 women undergoing hysterectomy for benign non-tubal gynaecological conditions.PARTICIPANTS/MATERIALS, SETTING, METHODS: The tubal epithelium and longitudinal smooth muscle fibres were isolated, cultured and treated with UPA at graded concentrations of 0, 20, 200 and 2000 ng/ml, and mifepristone at graded concentrations of 0, 300, 3000 and 30 000 ng/ml, respectively. After treatment, ciliary beat frequency was determined using a photometric method. Basal tone, amplitude and frequency of muscular contraction were recorded through a force transducer. The mRNA expression of progesterone receptor (total and PR-B isoform), glycodelin and adrenomedullin were determined by real-time quantitative PCR.MAIN RESULTS AND THE ROLE OF CHANCE: There was an overall dose-dependent suppressive effect on ciliary beat frequency (P < 0.0001) after treatment with UPA at all concentrations and with mifepristone at 3000 ng/ml or above. The basal tone, amplitude and frequency of muscular contractions were significantly reduced (P < 0.05) after treatment with UPA at 200 ng/ml or above, and with mifepristone at 3000 ng/ml or above. UPA treatment at 200 ng/ml or above significantly up-regulated the mRNA expression of progesterone receptor and glycodelin and down-regulated the mRNA expression of adrenomedullin in Fallopian tube tissue (P < 0.05).LIMITATIONS, REASONS FOR CAUTION: Whether or not the tubal effect may translate into additional mechanisms for contraceptive action in vivo is uncertain.WIDER IMPLICATIONS OF THE FINDINGS: The clinical relevance of UPA with regard to contraceptive activity is worthy of further exploration.STUDY FUNDING/COMPETING INTEREST(S): The study was supported by a Seed Fund from the Centre of Reproduction, Development and Growth, Faculty of Medicine, the University of Hong Kong. All authors have no competing interest to declare.