The ontogeny of kisspeptin receptor in the uterine contractions in rats: Its possible role in the quiescence of non-pregnant and pregnant uteri

Eur J Pharmacol. 2021 Apr 5;896:173924. doi: 10.1016/j.ejphar.2021.173924. Epub 2021 Feb 3.


The objectives of this study were to investigate the effects of KISS1 94-121 fragment on the contractility of non-pregnant and pregnant rat uteri, and to determine the uterine and myometrial expressions of Kiss1r. Uterine muscle strips were obtained from non-pregnant Sprague-Dawley rats in oestrous phase and from pregnant rats on gestational days 5, 15, 18, 20 or 22. The in vitro contractility measurements were carried out in an isolated organ bath in the presence of KISS1 94-121. Experiments with 5-day pregnant tissues were also performed in the presence of kisspeptin-234 trifluoroacetate. The mRNA and protein expressions of Kiss1r were measured by RT-PCR and Western blot analysis, while localizations of receptors were defined by fluorescent immunohistochemistry. KISS1 94-121 induced a dose-dependent relaxation both in non-pregnant and pregnant intact and endometrium-denuded uteri. A gradual decrease was found in the uterine expressions of Kiss1r mRNA and protein towards the end of the gestational period, and it was further confirmed by the immunohistochemical results. The significant majority of Kiss1r is found in the myometrium, however the few endometrial Kiss1r also influences the uterine contractions. The relaxing effect of kisspeptin is continuously reduced towards the end of gestational period in parallel with the reduction of Kiss1r expression. Our results suggest a putative role of kisspeptin in the maintenance of uterine quiescence that may have significance in miscarriage or preterm contractions.

Keywords: Contractility; Kisspeptin; Pregnancy; Rat; Uterus.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Endometrium / drug effects
  • Endometrium / metabolism
  • Female
  • In Vitro Techniques
  • Kisspeptins / pharmacology*
  • Myometrium / drug effects*
  • Myometrium / metabolism
  • Peptide Fragments / pharmacology*
  • Pregnancy
  • Rats, Sprague-Dawley
  • Receptors, Kisspeptin-1 / agonists*
  • Receptors, Kisspeptin-1 / genetics
  • Receptors, Kisspeptin-1 / metabolism
  • Signal Transduction
  • Uterine Contraction / drug effects*


  • Kiss1r protein, rat
  • Kisspeptins
  • Peptide Fragments
  • Receptors, Kisspeptin-1