title: Role of ghrelin in fertilization, early embryo development, and implantation periods.
abstract: In order to clarify the physiological role of ghrelin in gestation, we evaluated the effects of administration of exogenous ghrelin (2 or 4 nmol/animal per day) or its antagonist (6 nmol/animal per day of (d-Lys3)GHRP6) on fertilization, early embryo development, and implantation periods in mice. Three experiments were performed, treating female mice with ghrelin or its antagonist: i) starting from 1 week before copulation to 12 h after copulation, mice were killed at day 18 of gestation; ii) since ovulation induction until 80 h later, when we retrieved the embryos from oviducts/uterus, and iii) starting from days 3 to 7 of gestation (peri-implantation), mice were killed at day 18. In experiments 1 and 3, the antagonist and/or the highest dose of ghrelin significantly increased the percentage of atrophied fetuses and that of females exhibiting this finding or a higher amount of corpora lutea compared with fetuses (nCL/nF) (experiment 3: higher nCL/nF-atrophied fetuses: ghrelin 4, 71.4-71.4% and antagonist, 75.0-62.5% vs ghrelin 2, 46.2-15.4% and control, 10-0.0%; n=7-13 females/group; P<0.01). In experiment 2, the antagonist diminished the fertilization rate, and both, ghrelin and the antagonist, delayed embryo development (blastocysts: ghrelin 2, 62.5%; ghrelin 4, 50.6%; and antagonist, 61.0% vs control 78.4%; n=82-102 embryos/treatment; P<0.0001). In experiment 3, additionally, ghrelin (4 nmol/day) and the antagonist significantly diminished the weight gain of fetuses and dams during pregnancy. Our results indicate that not only hyperghrelinemia but also the inhibition of the endogenous ghrelin effects exerts negative effects on the fertilization, implantation, and embryo/fetal development periods, supporting the hypothesis that ghrelin (in 'adequate' concentrations) has a physiological role in early gestational events.
authors.affiliation: Facultad de Ciencias MédicasInstituto de Fisiología, Universidad Nacional de Córdoba, Santa Rosa 1085, X5000ESU Córdoba, Argentina.
authors.forename: Eugenia Mercedes
authors.initials: EM
authors.lastname: Luque
authors.affiliation: Facultad de Ciencias MédicasInstituto de Fisiología, Universidad Nacional de Córdoba, Santa Rosa 1085, X5000ESU Córdoba, Argentina.
authors.forename: Pedro Javier
authors.initials: PJ
authors.lastname: Torres
authors.affiliation: Facultad de Ciencias MédicasInstituto de Fisiología, Universidad Nacional de Córdoba, Santa Rosa 1085, X5000ESU Córdoba, Argentina.
authors.forename: Nicolás
authors.initials: N
authors.lastname: de Loredo
authors.affiliation: Facultad de Ciencias MédicasInstituto de Fisiología, Universidad Nacional de Córdoba, Santa Rosa 1085, X5000ESU Córdoba, Argentina.
authors.forename: Laura María
authors.initials: LM
authors.lastname: Vincenti
authors.affiliation: Facultad de Ciencias MédicasInstituto de Fisiología, Universidad Nacional de Córdoba, Santa Rosa 1085, X5000ESU Córdoba, Argentina.
authors.forename: Graciela
authors.initials: G
authors.lastname: Stutz
authors.affiliation: Facultad de Ciencias MédicasInstituto de Fisiología, Universidad Nacional de Córdoba, Santa Rosa 1085, X5000ESU Córdoba, Argentina.
authors.forename: María Emilia
authors.initials: ME
authors.lastname: Santillán
authors.affiliation: Facultad de Ciencias MédicasInstituto de Fisiología, Universidad Nacional de Córdoba, Santa Rosa 1085, X5000ESU Córdoba, Argentina.
authors.forename: Rubén Daniel
authors.initials: RD
authors.lastname: Ruiz
authors.affiliation: Facultad de Ciencias MédicasInstituto de Fisiología, Universidad Nacional de Córdoba, Santa Rosa 1085, X5000ESU Córdoba, Argentina.
authors.forename: Marta Fiol
authors.initials: MF
authors.lastname: de Cuneo
authors.affiliation: Facultad de Ciencias MédicasInstituto de Fisiología, Universidad Nacional de Córdoba, Santa Rosa 1085, X5000ESU Córdoba, Argentina acmartini2000@yahoo.com.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Martini
mesh_terms: D000818:Animals; D003307:Copulation; D003338:Corpus Luteum / Q000166:cytology / Q000187:drug effects; D010064:Embryo Implantation / Q000187:drug effects*; D004622:Embryo, Mammalian / Q000166:cytology* / Q000187:drug effects*; D005260:Female; D005306:Fertilization / Q000187:drug effects* / Q000502:physiology; D054439:Ghrelin / Q000494:pharmacology*; D051379:Mice; D011247:Pregnancy
chemical_list: D054439:Ghrelin