RESUMO
Metadata analysis of public microarray datasets using bioinformatics tools has been successfully used in several biomedical fields in the search for biomarkers. In reproductive science, there is an urgent need for the establishment of oocyte quality biomarkers that could be used in the clinical environment to increase the chances of successful outcomes in treatment cycles. Adaptive cellular processes observed in cumulus oophorus cells reflect the conditions of the follicular microenvironment and may thus bring relevant information of oocyte's conditions. Here we analyzed human cumulus cells gene expression datasets in search of predictors of oocyte quality, a strategy which uncovered several cellular processes positively and negatively associated with embryo development and pregnancy potential. Secondly, the expression levels of genes that were present in the majority of processes observed were validated in house with clinical samples. Our data confirmed the association of the selected biomarkers with blastocyst formation and pregnancy potential rates, independently of patients' clinical characteristics such as diagnosis, age, BMI, and stimulation protocol applied. This study shows that bioinformatic analysis of cellular processes can be successfully used to elucidate possible oocyte quality biomarkers. Our data reinforces the need to consider clinical characteristics of patients when selecting relevant biomarkers to be used in the clinical environment and suggests a combination of positive (PTGS2) and negative (CYPB1) quality biomarkers as a robust strategy for a complementary oocyte selection tool, potentially increasing assisted reproduction success rates. Also, GPX4 expression as pregnancy potential biomarker is indicated here as a possibility for further investigations.
Assuntos
Células do Cúmulo , Oócitos , Gravidez , Feminino , Humanos , Células do Cúmulo/metabolismo , Oócitos/metabolismo , Biomarcadores/metabolismo , Desenvolvimento Embrionário/genética , Ciclo-Oxigenase 2/metabolismoRESUMO
PURPOSE: To study whether the cumulus cell antioxidant system varies accordingly to patients clinical characteristics' as age, infertility diagnosis, BMI, and stimulation protocol applied and if the antioxidant profile of cumulus cells could be used as a predictor of embryo development. METHODS: A prospective study including 383 human cumulus samples provided by 191 female patients undergoing intracytoplasmic sperm injection during in vitro fertilization treatments from a local in vitro fertilization center and processed in university laboratories. Catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST) enzyme activity levels and reduced glutathione (GSH) levels were measured in cumulus oophorus cells individually collected from each aspirated cumulus-oocyte complex, and the results of each sample were compared considering the oocytes outcome after ICSI and patients clinical characteristics. A total of 223 other human cumulus samples from previous studies were submitted to a gene expression meta-analysis. RESULTS: The antioxidant system changes dramatically depending on patients' age, infertility diagnosis, stimulation protocol applied, and oocyte quality. SOD activity in cumulus cells revealed to be predictive of top-quality blastocysts for young patients with male factor infertility (P < 0.05), while GST levels were shown to be extremely influenced by infertility cause (P < 0.0001) and stimulation protocol applied (P < 0.05), but nonetheless, it can be used as a complementary tool for top-quality blastocyst prediction in patients submitted to intracytoplasmic sperm injection technique (ICSI) by male factor infertility (P < 0.05). CONCLUSION: Through a simple and non-invasive analysis, the evaluation of redox enzymes in cumulus cells could be used to predict embryo development, in a personalized matter in specific patient groups, indicating top-quality oocytes and improving success rates in in vitro fertilization treatments. TRIAL REGISTRATION: The trial was registered at UFRGS Research Ethics Committee and Plataforma Brasil under approval number 68081017.2.0000.5347 in June 6, 2019.
Assuntos
Células do Cúmulo , Infertilidade Masculina , Antioxidantes/metabolismo , Células do Cúmulo/fisiologia , Desenvolvimento Embrionário/genética , Feminino , Fertilização in vitro , Humanos , Infertilidade Masculina/metabolismo , Masculino , Oócitos/metabolismo , Estudos Prospectivos , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismoRESUMO
Foram analisados, retrospectivamente, 83 casos de insuficiência Renal Aguda (IRA), sendo 47 pacientes do sexo masculino e 36 do sexo feminino, com média de idade de 48 anos. Dos casos estudados 71% foram clínicos, 19% cirúrgicos e 10% obstétricos. A principal causa etiológica foi representada por hipovolemia a 31%, seguida por septicemia 23% e nefrotoxinas 8%. As complicaçöes mais comuns foram acidose, hiperpotassemia e alteraçöes neurológicas. Anúria ocorreu em 42% dos pacientes. 46% dos pacientes realizaram diálise peritoneal. Evoluiram favoravelmente 33% dos pacientes, foram à óbito 61% e desenvolveram insuficiência renal crônica (IRC) 6% dos pacientes. A maior mortalidade foi observada no grupo de pacientes cirúrgicos e naqueles com patologias associadas. Os resultados obtidos demonstram que o prognóstico da IRA é reservado principalmente por estar associado a outras condiçöes clínicas