RESUMO
The constant decline in fertility and older reproductive age is the major cause of low clinical pregnancy rates in industrialised countries. Epigenetic mechanisms impact on proper embryonic development in women undergoing in vitro fertilisation (IVF) protocols. Here, we describe the main epigenetic modifications that may influence female reproduction and could affect IVF success.
Assuntos
Metilação de DNA , Infertilidade Feminina , Gravidez , Feminino , Humanos , Idoso , Taxa de Gravidez , Fertilização in vitro/efeitos adversos , Infertilidade Feminina/genética , Infertilidade Feminina/terapia , FertilidadeRESUMO
PURPOSE: Long non-coding RNAs (lncRNAs) control gene expression at multiple levels. By interacting with microRNAs (miRNAs), they regulate their mRNA targets creating dynamic regulatory networks involved in different cellular processes. Their role in follicle development and oocyte maturation has recently emerged. lncRNA deregulation has been found associated with different pathological conditions. In this study, we identified differentially expressed lncRNAs in cumulus cells (CCs) isolated from MII oocytes of advanced maternal age women and proposed ceRNA-networks involved in signaling pathways crucial in ovarian folliculogenesis and female germ cell maturation. METHODS: We performed a high-throughput analysis of the expression profile of 68 lncRNAs from CCs of aged and young women by using NanoString technology. By miRNet, TarPmiR, miRTarBase, OKdb, and KEGG we predicted some ceRNA-networks involving the differentially expressed (DE) lncRNAs, miRNA interactors, and their mRNA target genes. RESULTS: We identified 28 lncRNAs down-regulated in CC samples from aged women. The analysis revealed that the miRNAs binding 11 of the DE lncRNAs and their mRNA targets are included in ceRNA-networks involved in the regulation of the PI3K-Akt, FOXO, and p53 signaling pathways. CONCLUSION: We proposed that the lncRNA down-regulation in CCs from aged women could influence the expression of genes encoding proteins deregulated in reproductive aging. A better understanding of the interplay of lncRNA-miRNA-mRNA networks in human CCs could increase our knowledge about the mechanisms of regulation of gene expression involved in aging, lead to the development of novel therapeutics, and improve reproductive outcomes in aged women.
Assuntos
MicroRNAs , RNA Longo não Codificante , Idoso , Envelhecimento/genética , Células do Cúmulo/metabolismo , Regulação para Baixo/genética , Feminino , Redes Reguladoras de Genes/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
INTRODUCTION: Rectosigmoid endometriosis and Dolichocolon can both present with a triad of chronic abdominal pain, constipation and bloating. The relationship between these two pathologies is unknown. The present study aims to determine the frequency of DC in women with rectosigmoid endometriosis and its possible impact on pre- and post-operative symptoms. MATERIAL AND METHODS: We conducted a retrospective cohort study on 113 consecutive patients submitted to magnetic resonance imaging enema and subsequent complete surgical removal for symptomatic rectosigmoid endometriosis between June 2015 to June 2018. Dolichocolon is an anatomic variant characterized by redundancies and lengthening of the colon. We divided our study population according to its presence or absence. The two groups were compared in terms of demographic data, surgical findings and pre- and post-operative clinical variables. Pain symptoms were assessed through numerical rating scale from 0 to 10. Bowel complaints included constipation, bloating and diarrhea. RESULTS: Thirty-five patients (31 %) presented a dolichocolon at magnetic resonance imaging enema. The two groups were comparable in terms of demographic data, pre-operative clinical variables and surgical findings. At 6-month follow-up, there was a significant improvement of symptoms, except for constipation and bloating in dolichocolon group. In particular, we observed with a statistical difference (p < .05) the persistence of constipation and bloating in dolichocolon group compared to non-dolichocolon group. CONCLUSIONS: Dolichocolon was observed in one third patients with rectosigmoid endometriosis and could influence surgical outcomes for rectosigmoid endometriosis in terms of relief of bowel symptoms.
Assuntos
Colo/patologia , Doenças do Colo/patologia , Doenças do Colo/cirurgia , Endometriose/cirurgia , Doenças Retais/cirurgia , Doenças do Colo Sigmoide/cirurgia , Adulto , Doenças do Colo/fisiopatologia , Constipação Intestinal , Diarreia , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Dor , Doenças Retais/patologia , Doenças Retais/fisiopatologia , Estudos Retrospectivos , Doenças do Colo Sigmoide/patologia , Doenças do Colo Sigmoide/fisiopatologia , Resultado do TratamentoRESUMO
OBJECTIVES: The aim of this study was to evaluate the diagnostic accuracy of a specific protocol of computed tomography-colonography with intravenous contrast medium and urographic phase, which combined simultaneously the study of the intestinal and urinary tract, in the preoperative evaluation of women with deep infiltrating endometriosis (DIE) of anterior and posterior pelvic compartments. METHODS: We retrospectively analyzed 73 women who underwent 74 computed tomography-colonography with intravenous contrast medium and urographic phase examinations for strong clinical suspicion of DIE. All the women had surgical confirmation. RESULTS: Computed tomography-colonography with intravenous contrast medium and urographic phase in detecting DIE rectosigmoid involvement had a sensitivity of 82.3% and a specificity of 66.7%, while in detecting DIE urinary tract involvement had a sensitivity of 45.9% and a specificity of 78.4%. CONCLUSIONS: Computed tomography-colonography with intravenous contrast medium and urographic phase is a useful technique for the preoperative planning of selected women with DIE, in particular, for the detection of sigmoid colon and bladder lesions especially when performed with a dose reduction protocol.
Assuntos
Meios de Contraste/administração & dosagem , Endometriose/diagnóstico por imagem , Intestinos/diagnóstico por imagem , Pelve/diagnóstico por imagem , Sistema Urinário/diagnóstico por imagem , Administração Intravenosa , Adulto , Colonografia Tomográfica Computadorizada , Feminino , Humanos , Pessoa de Meia-Idade , Imagem Multimodal , Estudos Retrospectivos , Sensibilidade e Especificidade , UrografiaRESUMO
BACKGROUND/AIMS: FSH receptor (FSHR) Ala307Thr and Asn680Ser and LHß chain (LHB) Trp28Arg and Ile35Thr polymorphisms affect the response to pharmacological ovarian stimulation with r-FSH in women undergoing assisted reproductive treatment (ART). Here, we evaluated the expression level of selected genes involved in follicle maturation and the possible onset of apoptosis in cumulus cells of patients with single and double FSHR and LHB polymorphisms, as potential markers of oocyte competence. METHODS: Cumulus cells from 36 stimulated patients were collected and SNP genotyping performed by PCR. Gene expression was evaluated through real-time PCR, and apoptosis estimated via TUNEL assay, and cleaved caspase-3 and pAKT immunostaining. RESULTS: The cumulative data show significant correlations indicating that the genetic alteration of FSHR and/or LHB genes may lead to perturbations of the signaling network programmed to granulosa cell survival and follicle development. Notably, when double heterozygotes were compared to the rest of the patients, a higher level of apoptosis in terms of both DNA fragmentation index and amount of active caspase-3 was observed in cumulus cells. CONCLUSIONS: These results may help to define personalized stimulation protocols in ART programs, to increase the success rate of ICSI procedures in accordance with the polymorphic condition of the individual patient.
Assuntos
Fertilização in vitro , Hormônio Luteinizante Subunidade beta/genética , Receptores do FSH/genética , Adulto , Apoptose , Busserrelina/administração & dosagem , Caspase 3/metabolismo , Células Cultivadas , Células do Cúmulo/citologia , Células do Cúmulo/metabolismo , Fragmentação do DNA , Feminino , Expressão Gênica , Frequência do Gene , Genótipo , Hormônio Liberador de Gonadotropina/agonistas , Haplótipos , Heterozigoto , Humanos , Hibridização in Situ Fluorescente , Análise Multivariada , Oócitos/citologia , Oócitos/metabolismo , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-akt/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de SinaisRESUMO
PURPOSE: To compare the diagnostic accuracy of transvaginal sonography (TVS) and computed tomography-colonography with contrast media and urographic phase (CTCU) in the preoperative detection of deep infiltrating endometriosis (DIE). MATERIALS AND METHODS: Forty-seven patients with clinical suspicion of DIE underwent preoperative TVS and CTCU. Imaging data were compared with histopathologic analysis. Sensitivity, specificity, positive and negative predictive values and test accuracies of the two modalities were calculated. RESULTS: For diagnosing intestinal DIE, TVS and CTCU had a sensitivity of 98 and 71%, specificity of 33 and 50%, positive predictive value of 91 and 91%, negative predictive value of 67 and 20%, accuracy of 89 and 68%, respectively. For diagnosing ureteral DIE, TVS and CTCU had a sensitivity of 10 and 60%, specificity of 94.8 and 70.2% on the right; sensitivity of 28.5 and 57.1%, specificity of 96.3 and 76.9% on the left, respectively. CONCLUSION: TVS should be regarded as an accurate, radiation-free first-line diagnostic modality for patients with suspicion of posterior endometriosis. CTCU should be regarded as a complementary imaging modality, particularly for sigmoid or ureteral endometriosis.
Assuntos
Colonografia Tomográfica Computadorizada/métodos , Meios de Contraste , Endometriose/diagnóstico por imagem , Pelve/diagnóstico por imagem , Intensificação de Imagem Radiográfica/métodos , Ultrassonografia/métodos , Urografia/métodos , Adulto , Estudos Transversais , Endometriose/patologia , Feminino , Humanos , Pelve/patologia , Projetos Piloto , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Sistema Urinário/diagnóstico por imagem , Vagina/diagnóstico por imagemRESUMO
OBJECTIVE: To present a case of partial 6q trisomy diagnosed prenatally. METHOD: A 28-year-old woman underwent genetic amniocentesis at 23 weeks of gestation on the detection of an enlarged nuchal fold (8.5 mm), which was the only clinical abnormality on routine ultrasound examination. Fetal karyotyping revealed a partial trisomy 6q (q21-q22) caused by a balanced maternal chromosomal insertion. RESULTS: A female infant was delivered at 38 weeks of gestation. At birth, minor dysmorphisms were recorded, which included low set ears, macrocephaly and a webbed neck. At 17 months of age, neurological developmental assessment was normal. CONCLUSIONS: The appearance of phenotypic expression and clinical outcome of partial 6q trisomy depends on the specific chromosomal region involved in the segmental aneusomy.