Ulipristal acetate resembles mifepristone in modulating human fallopian tube function

Hum Reprod. 2014 Oct 10;29(10):2156-62. doi: 10.1093/humrep/deu210. Epub 2014 Aug 19.

Abstract

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.

Keywords: ciliary beat; human Fallopian tube; mifepristone; muscular contraction; ulipristal acetate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenomedullin / metabolism
  • Cilia / drug effects
  • Cilia / physiology
  • Fallopian Tubes / drug effects*
  • Fallopian Tubes / physiology
  • Female
  • Glycodelin
  • Glycoproteins / metabolism
  • Humans
  • Mifepristone / pharmacology*
  • Muscle Contraction / drug effects
  • Norpregnadienes / pharmacology*
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Receptors, Progesterone / metabolism

Substances

  • Glycodelin
  • Glycoproteins
  • Norpregnadienes
  • PAEP protein, human
  • RNA, Messenger
  • Receptors, Progesterone
  • Adrenomedullin
  • Mifepristone
  • ulipristal acetate