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

Annamária Schaffer,Judit Hajagos-Tóth,Eszter Ducza,Nikolett Bódi,Mária Bagyánszki,Zita Szalai,Róbert Gáspár

doi:10.1016/j.ejphar.2021.173924

Annamária Schaffer, Judit Hajagos-Tóth + Show 5 more

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https://doi.org/10.1016/j.ejphar.2021.173924

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Abstract

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.

Highlights

Several neuropeptides regulate uterine smooth muscle contractions
Since among the neuropeptides there is no data available regarding the direct involvement of kisspeptin in uterine contractility, our aim was to investigate the effects of this neuropeptide on the contractions of nonpregnant and pregnant rat uteri
Several neuropeptides have been shown to affect smooth muscle function, but only a few studies have investigated the local effects of these peptides in the uterus

Summary

Introduction

Several neuropeptides regulate uterine smooth muscle contractions. The uterine oxytocin receptors are markedly upregulated, the responsiveness of the myome trium is intensified (Blanks and Thornton, 2003; Fuchs et al, 1984). Despite the controversial studies reporting that maternal plasma con centration may vary between individuals, oxytocin serum levels appear to gradually increase in most human pregnancies with peak concentra tions at birth (De Geest et al, 1985). The sensory neuropeptide calcitonin gene-related peptide (CGRP) has relaxant effects on different types of smooth muscles. CGRP has been shown to inhibit uterine contractions in both human and rat studies (Pennefather et al, 1990; Samuelson et al, 1985). CGRP caused dose-dependent relaxation of spontaneous and electric field stimulated contractions. A loss of its action was observed at the end of gestation and after delivery (Anouar et al, 1998)

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