Human reproduction (Oxford, England) · 2014
Ulipristal acetate resembles mifepristone in modulating human fallopian tube function.
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Li Hang Wun Raymond, Liao Su-Bin, Yeung William Shu-Biu, Ng Ernest Hung-Yu, O Wai-Sum, Ho Pak-Chung
Аннотация
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 INTERESTS: 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.
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 INTERESTS: 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.