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

Abstract

The objectives of this study were to investigate the effects of KISS1 94-121 fragment on the contractility of nonpregnant 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.

The ontogenies of endometrial and myometrial leptin and adiponectin receptors in pregnant rats: Their putative impact on uterine contractility

“…On the last days of gestation (days 20 and 22), the expression of endometrial receptors is negligible, therefore myometrial LEPRs are responsible for the responses, but they may lose their significance in relaxation towards labor. This phenomenon would not be unique, since we made a similar assumption in our previous studies with kisspeptin [37]. We hypothesize that in nonpregnant cases and in the early and mid-terms, both endometrial and myometrial leptin receptors are responsible for relaxation.…”

High Fat High Sucrose Diet Modifies Uterine Contractility and Cervical Resistance in Pregnant Rats: The Roles of Sex Hormones, Adipokines and Cytokines

“…Conversely leptin did not show any effect on PGF 2α -induced uterine contractions on the last day of the gestation period. The effects of these adipokines in SD rats are in harmony with our earlier experiments [ 13 , 14 ]. The HFHSD-induced relaxing effect of adipokines further confirms obesity-induced uterine dystocia.…”

“…Kisspeptin is better known as a neuropeptide participating in the control of reproductive processes [ 30 ], but in obesity this peptide behaves as an adipokine rather than a neuropeptide [ 31 ]. The relaxing effect of kisspeptin on uterine contractions has been identified in pregnant rats along with the ontogeny of the kisspeptin receptor [ 13 ].…”

“…Since both the increase in receptor expression and plasma level can enhance the effect of a given adipokine, these results suggest that the leptin pathway has the strongest, while the adiponectin pathway has the weakest (or neutral), influence on HFHSD-induced modifications in uterine contractions. Our previous studies revealed that both leptin and kisspeptin have a relaxing effect on last-day pregnant uteri [ 13 , 14 ], therefore we anticipated that these alterations should reduce uterine contractions.…”

“…Furthermore, the enlarged adipocyte undergoes continuous remodeling from hyperplasia to hypertrophy, therefore the synthesis of these adipokines is also altered in obesity [ 11 , 12 ]. The ontogeny of kisspeptin, leptin and adiponectin receptors through the gestation period and the effects of adipokines on uterine contractions have been proved in rats [ 13 , 14 ]. However, no data are available about their effects on uterine contraction in obese pregnant rats.…”