title: Beyond the brain-Peripheral kisspeptin signaling is essential for promoting endometrial gland development and function.
abstract: Uterine growth and endometrial gland formation (adenogenesis) and function, are essential for fertility and are controlled by estrogens and other regulators, whose nature and physiological relevance are yet to be elucidated. Kisspeptin, which signals via Kiss1r, is essential for fertility, primarily through its central control of the hypothalamic-pituitary-ovarian axis, but also likely through peripheral actions. Using genetically modified mice, we addressed the contributions of central and peripheral kisspeptin signaling in regulating uterine growth and adenogenesis. Global ablation of Kiss1 or Kiss1r dramatically suppressed uterine growth and almost fully prevented adenogenesis. However, while uterine growth was fully rescued by E2 treatment of Kiss1(-/-) mice and by genetic restoration of kisspeptin signaling in GnRH neurons in Kiss1r(-/-) mice, functional adenogenesis was only marginally restored. Thus, while uterine growth is largely dependent on ovarian E2-output via central kisspeptin signaling, peripheral kisspeptin signaling is indispensable for endometrial adenogenesis and function, essential aspects of reproductive competence.
authors.affiliation: Department of Cell Biology, Physiology &Immunology, Faculty of Medicine and Instituto Maimonides de Investigacion Biomedica de Córdoba (IMIBIC)/Hospital Reina Sofia, University of Córdoba, Avda. Menéndez Pidal s/n, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: León
authors.affiliation: Department of Cell Biology, Physiology &Immunology, Faculty of Medicine and Instituto Maimonides de Investigacion Biomedica de Córdoba (IMIBIC)/Hospital Reina Sofia, University of Córdoba, Avda. Menéndez Pidal s/n, Spain.
authors.forename: Daniela
authors.initials: D
authors.lastname: Fernandois
authors.affiliation: The Children's Health Research Institute, London, Ontario, Canada.|Lawson Health Research Institute, London, Ontario, Canada.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Sull
authors.affiliation: The Children's Health Research Institute, London, Ontario, Canada.|Lawson Health Research Institute, London, Ontario, Canada.
authors.forename: Judith
authors.initials: J
authors.lastname: Sull
authors.affiliation: The Children's Health Research Institute, London, Ontario, Canada.|Lawson Health Research Institute, London, Ontario, Canada.|Department of Obstetrics and Gynaecology, Division of Reproductive Endocrinology and Infertility, London, Ontario, N6C 2V5, Canada.
authors.forename: Michele
authors.initials: M
authors.lastname: Calder
authors.affiliation: Department of Physiology, Southern Illinois University School of Medicine, Carbondale, IL 62901, USA.
authors.forename: Kanako
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Lawson Health Research Institute, London, Ontario, Canada.|Department of Physiology and Pharmacology, London, Ontario, N6C 2V5, Canada.|Department of Oncology, London, Ontario University of Western Ontario, London, Ontario, N6C 2V5, Canada.
authors.forename: Moshmi
authors.initials: M
authors.lastname: Bhattacharya
authors.affiliation: Department of Obstetrics and Gynaecology, Division of Reproductive Endocrinology and Infertility, London, Ontario, N6C 2V5, Canada.
authors.forename: Stephen
authors.initials: S
authors.lastname: Power
authors.affiliation: Department of Obstetrics and Gynaecology, Division of Reproductive Endocrinology and Infertility, London, Ontario, N6C 2V5, Canada.
authors.forename: George A
authors.initials: GA
authors.lastname: Vilos
authors.affiliation: Department of Obstetrics and Gynaecology, Division of Reproductive Endocrinology and Infertility, London, Ontario, N6C 2V5, Canada.
authors.forename: Angelos G
authors.initials: AG
authors.lastname: Vilos
authors.affiliation: Department of Cell Biology, Physiology &Immunology, Faculty of Medicine and Instituto Maimonides de Investigacion Biomedica de Córdoba (IMIBIC)/Hospital Reina Sofia, University of Córdoba, Avda. Menéndez Pidal s/n, Spain.|CIBEROBN, Instituto de Salud Carlos III, 14004 Córdoba, Spain.|FiDiPro Program, Department of Physiology, University of Turku, 20520 Turku, Finland.
authors.forename: Manuel
authors.initials: M
authors.lastname: Tena-Sempere
authors.affiliation: The Children's Health Research Institute, London, Ontario, Canada.|Lawson Health Research Institute, London, Ontario, Canada.|Department of Obstetrics and Gynaecology, Division of Reproductive Endocrinology and Infertility, London, Ontario, N6C 2V5, Canada.|Department of Physiology and Pharmacology, London, Ontario, N6C 2V5, Canada.
authors.forename: Andy V
authors.initials: AV
authors.lastname: Babwah
mesh_terms: D000818:Animals; D004717:Endometrium / Q000254:growth & development* / Q000378:metabolism; D004967:Estrogens / Q000235:genetics; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D059648:Kisspeptins / Q000235:genetics*; D051379:Mice; D009474:Neurons / Q000378:metabolism; D038081:Organogenesis / Q000235:genetics; D010053:Ovary / Q000254:growth & development / Q000378:metabolism; D000074502:Receptors, Kisspeptin-1 / Q000235:genetics*; D012098:Reproduction / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics; D014599:Uterus / Q000254:growth & development* / Q000378:metabolism
chemical_list: D004967:Estrogens; C491407:Kiss1 protein, mouse; C492248:Kiss1r protein, mouse; D059648:Kisspeptins; D000074502:Receptors, Kisspeptin-1; D007987:Gonadotropin-Releasing Hormone