RESUMEN
BACKGROUND: Serum amyloid A (SAA) is an acute phase protein expressed primarily in the liver in response to various injuries and inflammatory stimuli and is recognized as a modulator of inflammation. Ovarian reproductive functions including folliculogenesis and ovulation use inflammatory processes; thus, studying SAA in this context is of interest. OBJECTIVES: We investigated the expression and localization of SAA in ovarian developing follicles and its levels in follicular fluids. METHODS AND PARTICIPANTS: Nonradioactive in situ hybridization and immunohistochemical staining were applied on ovarian paraffin tissue sections. ELISA and RT-PCR were applied on follicular aspirates and blood samples from women undergoing controlled ovarian stimulation for in vitro fertilization. RESULTS: Expression of SAA mRNA and protein was found in follicular cells at all stages of follicular development, from primordial and primary follicles through antral follicles and corpora lutea. Expression was observed in granulosa, theca and luteal cells, and oocytes. Expression of SAA was also found in granulosa cells recovered from follicular aspirates. The SAA protein was detected in follicular fluids. Its levels were somewhat lower than in peripheral blood with strong correlation between the two compartments and with significant correlation with patient's body mass index. High follicular fluid SAA levels were associated with reduced pregnancy rate. CONCLUSIONS: SAA is locally produced in ovarian developing follicles and is a constituent of follicular fluids, suggesting its role within the follicular environment. Elevated follicular SAA levels are associated with decreased pregnancy rate and may signify lower reproductive performance.
Asunto(s)
Líquido Folicular/metabolismo , Regulación del Desarrollo de la Expresión Génica , Oogénesis , Folículo Ovárico/metabolismo , Ovulación/metabolismo , Proteína Amiloide A Sérica/metabolismo , Adulto , Índice de Masa Corporal , Estudios de Cohortes , Cuerpo Lúteo/citología , Cuerpo Lúteo/metabolismo , Cuerpo Lúteo/patología , Femenino , Fertilización In Vitro , Células de la Granulosa/citología , Células de la Granulosa/metabolismo , Células de la Granulosa/patología , Humanos , Infertilidad Femenina/sangre , Infertilidad Femenina/metabolismo , Infertilidad Femenina/patología , Infertilidad Femenina/terapia , Infertilidad Masculina , Masculino , Persona de Mediana Edad , Folículo Ovárico/citología , Folículo Ovárico/patología , Ovulación/sangre , Inducción de la Ovulación , Embarazo , Índice de Embarazo , Transporte de Proteínas , Proteína Amiloide A Sérica/genéticaRESUMEN
Growth factor signalling has important modulatory roles in the process of human follicular growth, oocyte maturation and corpus luteum (CL) formation. Recently, Sprouty-2, an inhibitor of receptor tyrosine kinase (RTK) signalling pathway was advocated as a marker of oocyte competence in the bovine ovary. We sought to study Sprouty-2 expression and regulation in the human ovary. RT-PCR was used to detect Sprouty-2 mRNA in human granulosa-lutein cells (GLC) collected from follicular aspiration of IVF patients. The effect of epidermal and fibroblast growth factors (EGF and FGF) on Sprouty-2 mRNA expression in GLC was studied using quantitative real-time PCR. Immunohistochemistry was performed on cultured GLC, human CL and stimulated rat ovary sections. Sprouty-2 mRNA was expressed in human GLC. EGF and basic FGF, but not FGF4 and FGF10, increased Sprouty-2 mRNA expression in GLC. The Sprouty protein was localized to GLC of early and late human CL but not to the theca cell layer. Immunostaining of developing rat CL confirmed the temporal and spatial expression of Sprouty in humans. The detection of Sprouty-2 mRNA and protein in human GLC may suggest a role for Sprouty-2 during the final stages of follicle maturation and CL formation.