title: Influence of leptin on in vitro maturation and steroidogenic secretion of cumulus-oocyte complexes through JAK2/STAT3 and MEK 1/2 pathways in the rabbit model.
abstract: Extreme body mass indexes may impair reproductive outcome in assisted reproductive technologies. Leptin reflects the amount of body fat and could act as a modulator of oocyte quality through activation of specific transcription factors. The aim of this work was to establish whether: 1) leptin influences meiotic and cytoplasmic oocyte maturation; 2) STAT3 and MAPK mediate the effects of leptin and 3) leptin modulates steroid secretion by cumulus-oocyte complexes (COC) during in vitro maturation (IVM). We confirmed immunolocalisation of leptin receptor in oocytes, cumulus/granulosa cells during the peri-ovulatory period. The confocal study showed that COC supplemented with 1, 10 and 100 ng/ml leptin had a significantly higher metaphase II (MII) percentage than those IVM without leptin (P<0.05) and a similar MII index compared to the group supplemented with 10% FCS. Leptin did not increase the percentage of cytoplasmically matured oocytes in terms of cortical granule migration rate, whereas a significantly higher index was found in the FCS group (P<0.001). Oestradiol concentrations in spent media were higher in the FCS group compared to other treatments (P<0.001). Leptin-stimulated nuclear oocyte maturation was significantly impaired when leptin-induced JAK2/STAT3 and MEK 1/2 activation was suppressed by the inhibitors (P<0.001). Steroid secretion of COC was not affected by leptin activation of JAK2/STAT3 or MEK 1/2 pathways. In conclusion, JAK2/STAT3 and MEK 1/2 pathways mediate the enhancement of nuclear oocyte maturation by leptin; however, neither cytoplasmic oocyte maturation nor steroidogenic response of COC were improved in the present rabbit model.
authors.affiliation: Departamento de Fisiología (Fisiología Animal), Facultad de Veterinaria, Universidad Complutense de Madrid, Ciudad Universitaria, s/n, 28040 Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Arias-Alvarez
authors.forename: R M
authors.initials: RM
authors.lastname: García-García
authors.forename: L
authors.initials: L
authors.lastname: Torres-Rovira
authors.forename: A
authors.initials: A
authors.lastname: González-Bulnes
authors.forename: P G
authors.initials: PG
authors.lastname: Rebollar
authors.forename: P L
authors.initials: PL
authors.lastname: Lorenzo
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054885:Cumulus Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000378:metabolism / Q000502:physiology*; D020738:Leptin / Q000494:pharmacology*; D048369:MAP Kinase Kinase 1 / Q000378:metabolism / Q000502:physiology*; D048370:MAP Kinase Kinase 2 / Q000378:metabolism / Q000502:physiology*; D023421:Models, Animal; D008954:Models, Biological; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009866:Oogenesis / Q000187:drug effects*; D011817:Rabbits; D050796:STAT3 Transcription Factor / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D012739:Gonadal Steroid Hormones; D020738:Leptin; D050796:STAT3 Transcription Factor; D053614:Janus Kinase 2; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2