RESUMEN
Hormonal ovarian stimulation may affect transcripts in somatic cells of cumulus-oocyte complexes (COCs) and affect the resulting oocyte quality. Here, in parallel with morphological classification and in vitro maturation (IVM) rate analysis, we investigated the expression of hyaluronan synthase 2 (HAS2), gonadotropic receptors (FSHR and LHR) and connexin 43 (GJA1) in cumulus cells (CCs) from goat COCs after multi-dose FSH (MD) or one-shot FSH/eCG (OS) treatments, using bovine COCs as control groups. The MD treatment produced more large follicles, and the resulting COCs had a better morphology and IVM rate than were obtained with OS. The OS treatment produced COCs with increased HAS2, FSHR, LHR and GJA1 expression. This gene expression pattern was also observed in the CCs of COCs that showed poor morphological characteristics. On the other hand, the mRNA levels were more similar between groups after IVM; FSHR and LHR were the main genes that showed decreased expression. Some events that occurred in bovine CCs during IVM, such as cell expansion, increased HAS2 expression and decreased GJA1 expression, were less evident or did not occur in goat COCs. In conclusion, increasing HAS2, FSHR, LHR and GJA1 expression in goat COCs does not confer greater meiotic competence to oocytes. Instead, it may result from poor regulation of gene expression in CCs by lower quality oocytes. Finally, cumulus expansion, together with HAS2 upregulation and GJA1 downregulation, seems to be more important for bovine COCs than for goat COCs. Additional studies are needed to investigate the importance of other HAS isoforms and connexins in goat COCs.
Asunto(s)
Gonadotropina Coriónica/farmacología , Células del Cúmulo/enzimología , Hormona Folículo Estimulante/farmacología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Glucuronosiltransferasa/metabolismo , Inducción de la Ovulación/veterinaria , Animales , Gonadotropina Coriónica/administración & dosificación , Células del Cúmulo/metabolismo , Combinación de Medicamentos , Femenino , Hormona Folículo Estimulante/administración & dosificación , Hormonas/administración & dosificación , Hormonas/farmacología , Sustancias para el Control de la Reproducción/administración & dosificación , Sustancias para el Control de la Reproducción/farmacologíaRESUMEN
It is questioned whether worsening of oocyte quality and oxidative stress (OS) are involved in the pathogenesis of infertility related to endometriosis and in compromised intracytoplasmic sperm injection (ICSI) outcomes. Cumulus cells (CCs) protect oocytes from entering apoptosis induced by OS. Thus, we carried out a case-control study comparing expression of superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2), and glutathione peroxidase 4 (GPX4; genes encoding for the main antioxidant enzymes) in CCs from mature oocytes of 26 infertile patients with minimal/mild endometriosis, 14 patients with moderate/severe endometriosis, and 41 controls undergoing controlled ovarian stimulation for ICSI, using real-time polymerase chain reaction. As a secondary objective, we investigated the interaction between the expression of these genes and clinical pregnancy (CP) by a statistical model. Only infertile women with moderate/severe endometriosis showed increased expression of the SOD1 in CCs compared to women with minimal/mild endometriosis and controls, with a positive interaction between increased expression and the occurrence of CP, suggesting that SOD1 might be a potential biomarker of CP following ICSI.
Asunto(s)
Células del Cúmulo/enzimología , Endometriosis/complicaciones , Infertilidad Femenina/etiología , Superóxido Dismutasa/genética , Adulto , Estudios de Casos y Controles , Endometriosis/diagnóstico , Femenino , Humanos , Infertilidad Femenina/diagnóstico , Infertilidad Femenina/enzimología , Infertilidad Femenina/genética , Infertilidad Femenina/terapia , Estudios Prospectivos , Reacción en Cadena en Tiempo Real de la Polimerasa , Técnicas Reproductivas Asistidas , Índice de Severidad de la Enfermedad , Superóxido Dismutasa-1 , Regulación hacia ArribaRESUMEN
Aromatase plays a fundamental role in the establishment of oocyte quality, which might be compromised in infertile women with endometriosis. The expression of the CYP19A1 gene (that encodes aromatase) was compared in cumulus cells and oestradiol concentrations in the follicular fluid of infertile women with and without endometriosis submitted to ovarian stimulation for intracytoplasmic sperm injection. Cumulus cells were isolated and the expression of the CYP19A1 was quantitated through real-time polymerase chain reaction. Oestradiol concentrations in follicular fluid were measured by chemiluminescence immunoassay. A lower expression of the CYP19A1 in the cumulus cells of infertile women with endometriosis was observed compared with controls (0.17 ± 0.13 and 0.56 ± 0.12, respectively), and no significant difference in the follicular fluid oestradiol concentrations was observed between groups. Our results show reduced expression of the CYP19A1 in cumulus cells of infertile women with endometriosis, which may play a role in the pathogenesis of endometriosis-related infertility.