title: The pregnant mouse uterus exhibits a functional kisspeptin/KISS1R signaling system on the day of embryo implantation.
abstract: BACKGROUND
  Expression of kisspeptin (protein) and Kiss1r (mRNA) was recently documented in the mouse uterus on D4 of pregnancy (the day of embryo implantation) suggesting that the uterine-based kisspeptin (KP)/kisspeptin receptor (KISS1R) signaling system regulates embryo implantation. Despite this important suggestion, it was never demonstrated that the uterus actually exhibits a functional KP/KISS1R signaling system on D4 of pregnancy. Thus, the goal of this study was to determine whether a functional KP/KISS1R signaling system exists in the mouse uterus on D4 of pregnancy.
  
  
  RESULTS
  Since kisspeptin/KISS1R signaling triggers the phosphorylation of the mitogen-activated protein kinases p38 and ERK1/2, through immunohistochemical analyses, we determined whether exogenously administered kisspeptin could trigger p38 and ERK1/2 phosphorylation in the uterus on D4 of pregnancy. The results clearly demonstrated that kisspeptin could and that its effects were mediated via KISS1R. Additionally, the robust kisspeptin-triggered response was observed in the pregnant uterus only. Finally, it was demonstrated that on D4 of pregnancy the Kiss1 null uterus expresses functional KISS1R molecules capable of mediating the effects of kisspeptin.
  
  
  CONCLUSIONS
  These results lead us to conclude that on D4 of pregnancy, the mouse uterus expresses a functional KP/KISS1R signaling system strengthening the possibility that this signaling system regulates embryo implantation. These findings strengthen the rationale for determining whether such a functional system exists in the uterus of the human female and if so, what role it might play in human pregnancy.
authors.affiliation: The Children's Health Research Institute, Victoria Research Laboratories, 800 Commissioners Road East, London, ON, Canada, N6C 2V5. mehr.fayazi@gmail.com.|Lawson Health Research Institute, London, ON, Canada. mehr.fayazi@gmail.com.|Department of Physiology and Pharmacology, London, ON, Canada, N6C 2V5. mehr.fayazi@gmail.com.
authors.forename: Mehri
authors.initials: M
authors.lastname: Fayazi
authors.affiliation: The Children's Health Research Institute, Victoria Research Laboratories, 800 Commissioners Road East, London, ON, Canada, N6C 2V5. michele.calder@schulich.uwo.ca.|Lawson Health Research Institute, London, ON, Canada. michele.calder@schulich.uwo.ca.|Department of Obstetrics and Gynaecology, Division of Reproductive Endocrinology and Infertility, London, ON, Canada, N6C 2V5. michele.calder@schulich.uwo.ca.
authors.forename: Michele
authors.initials: M
authors.lastname: Calder
authors.affiliation: Lawson Health Research Institute, London, ON, Canada. mbhattac@uwo.ca.|Department of Physiology and Pharmacology, London, ON, Canada, N6C 2V5. mbhattac@uwo.ca.|Department of Oncology, London, Ontario University of Western Ontario, London, ON, Canada, N6C 2V5. mbhattac@uwo.ca.
authors.forename: Moshmi
authors.initials: M
authors.lastname: Bhattacharya
authors.affiliation: Department of Obstetrics and Gynaecology, Division of Reproductive Endocrinology and Infertility, London, ON, Canada, N6C 2V5. george.vilos@lhsc.on.ca.
authors.forename: George A
authors.initials: GA
authors.lastname: Vilos
authors.affiliation: Department of Obstetrics and Gynaecology, Division of Reproductive Endocrinology and Infertility, London, ON, Canada, N6C 2V5. stephen.power@lhsc.on.ca.
authors.forename: Stephen
authors.initials: S
authors.lastname: Power
authors.affiliation: The Children's Health Research Institute, Victoria Research Laboratories, 800 Commissioners Road East, London, ON, Canada, N6C 2V5. ababwah@uwo.ca.|Lawson Health Research Institute, London, ON, Canada. ababwah@uwo.ca.|Department of Obstetrics and Gynaecology, Division of Reproductive Endocrinology and Infertility, London, ON, Canada, N6C 2V5. ababwah@uwo.ca.|Department of Physiology and Pharmacology, London, ON, Canada, N6C 2V5. ababwah@uwo.ca.
authors.forename: Andy V
authors.initials: AV
authors.lastname: Babwah
mesh_terms: D000818:Animals; D010064:Embryo Implantation / Q000502:physiology*; D005260:Female; D059648:Kisspeptins / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D000074502:Receptors, Kisspeptin-1; D015398:Signal Transduction / Q000502:physiology*; D014599:Uterus / Q000502:physiology*
chemical_list: C492248:Kiss1r protein, mouse; D059648:Kisspeptins; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1