The impact of obesity on pregnant rat uterine contractility: The roles of kisspeptin

[Speaker] Judit Hajagos-Toth:1
[Co-author] Anna Kothencz:1, Eszter Ducza:1, Kalman Szucs:1, Anita Sztojkov-Ivanov:1, Reza Samavati:1, Annamaria Schaffer:1, Orsolya Kovacs:1, Sandor Vari:2, Robert Gaspar:1
1:Department of Pharmacodynamics and Biopharmacy, University of Szeged, Hungary, 2:International Research and Innovation in Medicine Program Cedars - Sinai Medical Center, Los Angeles, CA, USA

Background: The increasing prevalence of maternal obesity is a major public health concern. It is associated with increased incidence of caesarean section and leads to both poor maternal and fetal outcomes. The adipocytes are producing adipokines such as kisspeptin that as a neuropeptide also take part in the regulation of reproduction. The main questions are the impact of obesity on the maternal and fetal outcomes and the myometrial effects of kisspeptin on the last day of pregnancy in normal and obese rats in vitro.
Methods: 3 weeks old SPRD rats were feeding with standard diet (SD) or high-fat high-sugar diet (HFHSD) until the end of pregnancy. Glucose tolerance test was carried out before and during pregnancy. Uteri were removed on the last day of pregnancy and contractions of uterine rings were measured in an organ bath. The contractions were stimulated with 25 mM KCl and cumulative-dose response curves were elicited in the presence of the kisspeptin (10-11-10-7 M). The mRNA and protein expression of the KISS1 receptors was determined by RT-PCR and Western blot analysis.
Results: The HFHSD caused significant maternal weight gain and decreased the glucose tolerance, weight of placentas and fetuses. The mRNA and protein expression of the KISS1 receptors was increased in obesity. Obesity resulted in poor spontaneous uterine contractility; however it increased the sensitivity of uterus against KCl. Kisspeptin caused dose-dependent uterine relaxation in the SD group; however it increased the uterine contraction in the HFHSD group.
Conclusions: Obesity increases the expression of KISS1-receptor in pregnant uteri,, alters the contractility of the myometrium and leads to placental and fetal growth retardation. Kisspeptin modifies the uterine contractions differently in normal and obese pregnancy. We suppose that kisspeptin may have a significant role in the obesity-induced alteration pregnant uterine contraction and fetal development.
Acknowledgement: This work was supported by Cedars Sinai Medical Center's International Research and Innovation in Medicine Program, the Association for Regional Cooperation in the Fields of Health, Science and Technology (RECOOP HST Association) and the participating Cedars-Sinai Medical Center - RECOOP Research Centers (CRRC).

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