RESUMO
Epigenetic regulation is an important entry point to study the pathogenesis of selective fetal growth restriction (sFGR), and an understanding of the role of long noncoding RNAs (lncRNAs) in sFGR is lacking. Our study aimed to investigate the potential role of a lncRNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), in sFGR using molecular biology experiments and gain- or loss-of-function assays. We found that the levels of MALAT1, ERRγ, and HSD17B1 were downregulated and that of miR-424 was upregulated in the placental shares of the smaller twins. Moreover, angiogenesis was impaired in the placental share of the smaller fetus and MALAT1 could regulate the paracrine effects of trophoblasts on endothelium angiogenesis and proliferation by regulating miR-424. In trophoblasts, MALAT1 could competitively bind to miR-424 to regulate the expression of ERRγ and HSD17B1, thus regulating trophoblast invasion and migration. MALAT1 overexpression could decrease apoptosis and promote proliferation, alleviating cell damage induced by hypoxia. Taken together, the downregulation of MALAT1 can reduce the expression of ERRγ and HSD17B1 by competitively binding to miR-424, impairing the proangiogenic effect of trophoblasts, trophoblast invasion and migration, and the ability of trophoblasts to compensate for hypoxia, which may be involved in the pathogenesis of sFGR through various aspects.
Assuntos
Movimento Celular , Proliferação de Células , Retardo do Crescimento Fetal , MicroRNAs , RNA Longo não Codificante , Trofoblastos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Humanos , Trofoblastos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Movimento Celular/genética , Feminino , Retardo do Crescimento Fetal/genética , Retardo do Crescimento Fetal/metabolismo , Retardo do Crescimento Fetal/patologia , Gravidez , Proliferação de Células/genética , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/genética , Apoptose/genética , Neovascularização Fisiológica/genética , Placenta/metabolismo , Estradiol DesidrogenasesRESUMO
OBJECTIVE: To evaluate obstetric outcomes in twin pregnancies of advanced maternal age (≥35 years). MATERIALS AND METHODS: A retrospective study involved 470 twin pregnancies in a single center from Sep. 1, 2012 to Mar. 31, 2015. Clinical characteristics and obstetric outcomes were recorded and compared among twin pregnancies who were classified as follows: age 20-29, 30-34, 35-39 and ≥40 years. RESULTS: The incidence of gestational diabetes (age 20-29 years 15.8%; 30-34 years 24.3%; 35-39 years 30.4%; ≥40 years 57.1%; p = 0.004) and premature delivery (20-29 years 58.6%; 30-34 years 69.1%; 35-39 years 72.2%; ≥40 years 85.7%; p = 0.001) significantly increased with increasing age whereas spontaneous abortion (20-29 years 27.6%; 30-34 years 11.6%; 35-39 years 11.4%; ≥40 years 0.0%; p = 0.021) decreased in twin pregnancies of advanced maternal age. In addition, the rate of postpartum hemorrhage increased almost continuously by age and advanced maternal age was described as a risk factor for postpartum hemorrhage (age 35-39, adjusted OR 3.377; 95% confidence interval 1729-6.598; p < 0.001; age ≥ 40, adjusted OR 10.520; 95% CI 1.147-96.492; p = 0.037). However, there was no significant difference between advanced maternal age and adverse neonatal outcomes. CONCLUSION: In twin pregnancies, advanced maternal age experienced significant higher risk of postpartum hemorrhage, gestational diabetes and premature delivery. Neither adverse neonatal outcomes nor stillbirth was significantly associated with maternal age.
Assuntos
Idade Materna , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Gravidez de Gêmeos/estatística & dados numéricos , Adulto , Fatores Etários , Estudos de Coortes , Feminino , Humanos , Incidência , Recém-Nascido , Gravidez , Estudos Retrospectivos , Adulto JovemRESUMO
Objective To demonstrate the correlation between nuclear and cytoplasmic G protein-coupled oestrogen receptor (GPR30) expression and clinicopathological features and outcome in patients with ovarian cancer. Methods Nuclear and cytoplasmic GPR30 expressions were determined using immunohistochemistry to identify the intracellular location in tissues from patients with ovarian cancer. Data were correlated with clinicopathological characteristics and outcomes. Results Tissue samples were obtained from 110 patients with epithelial ovarian cancer between 2005 and 2010. Nuclear GPR30 was significantly more frequent in the group of patients with recurrence. The presence of nuclear GPR30 predicted lower overall survival) and 5-year progression-free survival in all patients with ovarian cancer and overall survival in patients with high grade ovarian cancer. Cytoplasmic GPR30 was observed significantly more often in advanced ovarian cancer and did not predict survival. Conclusion This study showed that nuclear GPR30 is an independent negative prognostic indicator in patients with ovarian cancer, especially in those with a high grade malignancy.