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1.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(9): 912-916, 2021 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-34487543

RESUMO

MAMLD1 gene has been implicated in 46,XY disorders of sex development (DSD) in recent years. Patients carrying MAMLD1 gene variants showed a "continuous spectrum" of simple micropenis, mild, moderate and severe hypospadias with micropenis, cryptorchidism, split scrotum and even complete gonadal dysplasia. The function of MAMLD1 gene in sexual development has not been fully elucidated, and its role in DSD has remained controversial. This article has reviewed recent findings on the role of the MAMLD1 gene in DSD, including the MAMLD1 gene, its encoded protein, genetic variants, clinical phenotype and possible pathogenic mechanism in DSD.


Assuntos
Proteínas de Ligação a DNA , Transtornos do Desenvolvimento Sexual , Proteínas de Ligação a DNA/genética , Transtornos do Desenvolvimento Sexual/genética , Humanos , Masculino , Mutação , Proteínas Nucleares/genética , Fenótipo , Desenvolvimento Sexual , Fatores de Transcrição/genética
2.
AMA J Ethics ; 23(7): E550-556, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34351265

RESUMO

For years, physicians have debated how best to care for children with differences in sex development (DSD, also termed intersex). Stories of suffering of adults who underwent early surgical intervention for DSD have led many health organizations to call for deferral of unnecessary procedures. While some have instituted full deferral of cosmetic procedures, standard of care remains an interdisciplinary team approach informed by parents' wishes. As the medical community hesitates to institute full deferral, citing absence of long-term data, legislation restricting early procedures is mounting. This article highlights recent data from the DSD-LIFE Study and considers whether and to what extent they support deferral.


Assuntos
Transtornos do Desenvolvimento Sexual , Médicos , Adulto , Criança , Humanos , Pais , Desenvolvimento Sexual , Padrão de Cuidado
3.
Arch. argent. pediatr ; 119(4): 251-258, agosto 2021. tab, ilus
Artigo em Inglês, Espanhol | LILACS, BINACIS | ID: biblio-1280909

RESUMO

Introducción. El orquidómetro de Prader es el método estándar para medir el volumen testicular (VT) en niños y adolescentes. Objetivo. Evaluar la concordancia en la estimación del VT y del inicio puberal con las técnicas de orquidometría de Prader, Chipkevitch y Sotos. Métodos. Diseño descriptivo transversal realizado en varones de entre 9 y 20 años. Se midió el VT (ml) en cada adolescente con las técnicas de Prader (método de referencia), Chipkevitch (modelo gráfico) y Sotos (medición de ancho testicular con regla plástica y fórmula equivalente a ecuación elipsoide). Se excluyeron varones con patología urogenital y enfermedades que afectan el crecimiento testicular. Para la concordancia entre métodos, se utilizó kappa para el inicio puberal, y coeficiente de correlación intraclase (CCI) y gráficos de Bland-Altman (GBA) para el VT. Resultados. Se incluyeron 377 varones sanos. Para la concordancia en VT (ml), la comparación Prader-Chipkevitch obtuvo CCI: 0,994 y p < 0,001; y de CCI; 0,312 y p < 0,001 para la de Prader-Sotos. En los GBA se halló una media de las diferencias cercana a 0 ml en la comparación Prader-Chipkevitch y cercana a 8 ml en la de Prader-Sotos. El acuerdo en el inicio puberal obtuvo un valor de kappa 0,93 en la comparación Prader-Chipkevitch y de 0,75 en la de Prader-Sotos. Conclusión. Los orquidómetros de Prader y Chipkevitch tienen una excelente concordancia en la estimación del VT y el inicio puberal; por lo tanto, podrían intercambiarse en la atención diaria de varones adolescentes. El método de Sotos mostró una concordancia buena en la estimación del inicio puberal, pero baja en la medición del VT


Introduction. The Prader orchidometer is the standard method used to measure testicular volume (TV) in children and adolescents. Objective. To assess the concordance in the estimation of TV and puberty onset with the Prader, Chipkevitch, and Sotos orchidometric techniques. Methods. Cross-sectional descriptive study conducted among male children and adolescents aged 9-20 years. For each adolescent, TV was measured with the methods by Prader (gold standard), Chipkevitch (graphic model), and Sotos (measurement of testicular width with a plastic ruler and use of a formula equivalent to the ellipsoid equation). Male children and adolescents with urogenital conditions and disorders affecting testicular growth were excluded. Kappa statistics was used to determine concordance among methods for puberty onset, and intraclass correlation coefficient (ICC) and Bland-Altman (B&A) plots for TV. Results. In total, 377 healthy males were included. Regarding the concordance for TV (mL), the Prader-Chipkevitch comparison obtained an ICC of 0.994 and a p < 0.001; while the Prader-Soto comparison obtained an ICC of 0.312 and a p < 0.001. With the B&A plots, mean differences were close to 0 mL in the Prader-Chipkevitch comparison and close to 8 mL in the Prader-Sotos comparison. Concordance for puberty onset obtained a kappa value of 0.93 and 0.75 in the Prader-Chipkevitch and Prader-Sotos comparisons, respectively. Conclusion. The Prader and Chipkevitch orchidometers show an excellent concordance in estimating TV and puberty onset; therefore, both methods could be used interchangeably in the daily care of male adolescents. The Sotos method showed a high concordance in estimating pubertal onset, but low in measuring TV.


Assuntos
Humanos , Masculino , Criança , Adolescente , Testículo/anatomia & histologia , Desenvolvimento Sexual , Pediatria/instrumentação , Testículo/crescimento & desenvolvimento , Antropometria/instrumentação , Estudos Transversais , Puberdade
4.
Genes (Basel) ; 12(6)2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200177

RESUMO

The transcriptional regulation of gene expression in higher organisms is essential for different cellular and biological processes. These processes are controlled by transcription factors and their combinatorial interplay, which are crucial for complex genetic programs and transcriptional machinery. The regulation of sex-biased gene expression plays a major role in phenotypic sexual dimorphism in many species, causing dimorphic gene expression patterns between two different sexes. The role of transcription factor (TF) in gene regulatory mechanisms so far has not been studied for sex determination and sex-associated colour patterning in zebrafish with respect to phenotypic sexual dimorphism. To address this open biological issue, we applied bioinformatics approaches for identifying the predicted TF pairs based on their binding sites for sex and colour genes in zebrafish. In this study, we identified 25 (e.g., STAT6-GATA4; JUN-GATA4; SOX9-JUN) and 14 (e.g., IRF-STAT6; SOX9-JUN; STAT6-GATA4) potentially cooperating TFs based on their binding patterns in promoter regions for sex determination and colour pattern genes in zebrafish, respectively. The comparison between identified TFs for sex and colour genes revealed several predicted TF pairs (e.g., STAT6-GATA4; JUN-SOX9) are common for both phenotypes, which may play a pivotal role in phenotypic sexual dimorphism in zebrafish.


Assuntos
Desenvolvimento Sexual/genética , Fatores de Transcrição/genética , Proteínas de Peixe-Zebra/genética , Animais , Simulação por Computador , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Masculino , Caracteres Sexuais , Pigmentação da Pele/genética , Fatores de Transcrição/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/metabolismo
5.
BMC Genomics ; 22(1): 552, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34281525

RESUMO

BACKGROUND: The tiger frog (Hoplobatrachus rugulosus) is listed as a national Class II protected species in China. In the context of global warming, the sex ratio of amphibians will be affected, and the development of the population will be limited. Therefore, considering the potential for a decrease in the number of amphibians, studying sex evolution and molecular regulation of gonadal development in H. rugulosus, phenomenon that are currently unclear, is of great significance. RESULTS: Here, H. rugulosus was used to explore the mechanisms regulating gonadal development in amphibians. Illumina HiSeq 3000 was used to sequence the gonadal transcriptome of male and female H. rugulosus at two growth stages to identify genes related to gonadal development and analyze expression differences in the gonads. This analysis indicated that cyp17α, hsd3ß, hsd11ß1, cyp19α, and hsd17ß12 perform vital functions in sex development in amphibians. Specifically, the expression of cyp3α, cyp17α, hsd3ß, hsd11ß1, sox2, sox9, sox30, soat, cyp19α, hsd17ß12, and hspα1s was correlated with gonadal development and differentiation in H. rugulosus, as determined using the quantitative reverse transcriptase-polymerase chain reaction. CONCLUSION: Significant differences were found in the gonadal gene expression levels in H. rugulosus of both sexes, and we identified a steroid hormone synthesis pathway in this species and analyzed related gene expression, but the changes during sex differentiation were still unclear. To our knowledge, this report presents the first analysis of the H. rugulosus gonadal transcriptome and lays the foundation for future research.


Assuntos
Gônadas , Transcriptoma , Animais , Anuros/genética , China , Feminino , Masculino , Diferenciação Sexual/genética , Desenvolvimento Sexual
6.
Front Cell Infect Microbiol ; 11: 669088, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34268135

RESUMO

The human malaria parasite Plasmodium falciparum expresses variant PfEMP1 proteins on the infected erythrocyte, which function as ligands for endothelial receptors in capillary vessels, leading to erythrocyte sequestration and severe malaria. The factors that orchestrate the mono-allelic expression of the 45-90 PfEMP1-encoding var genes within each parasite genome are still not fully identified. Here, we show that the transcription factor PfAP2-O influences the transcription of var genes. The temporary knockdown of PfAP2-O leads to a complete loss of var transcriptional memory and a decrease in cytoadherence in CD36 adherent parasites. AP2-O-knocked-down parasites exhibited also significant reductions in transmission through Anopheles mosquitoes. We propose that PfAP2-O is, beside its role in transmission stages, also one of the virulence gene transcriptional regulators and may therefore be exploited as an important target to disrupt severe malaria and block parasite transmission.


Assuntos
Malária Falciparum , Plasmodium falciparum , Animais , Eritrócitos , Humanos , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Desenvolvimento Sexual , Fatores de Transcrição/genética , Transcrição Genética , Virulência/genética
7.
Int J Mol Sci ; 22(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206462

RESUMO

Human fetal gonads acquire endocrine steroidogenic capabilities early during their differentiation. Genetic studies show that this endocrine function plays a central role in the sexually dimorphic development of the external genitalia during fetal development. When this endocrine function is dysregulated, congenital malformations and pathologies are the result. In this review, we explain how the current knowledge of steroidogenesis in human fetal gonads has benefited from both the technological advances in steroid measurements and the assembly of detailed knowledge of steroidogenesis machinery and its expression in human fetal gonads. We summarise how the conversion of radiolabelled steroid precursors, antibody-based assays, mass spectrometry, ultrastructural studies, and the in situ labelling of proteins and mRNA have all provided complementary information. In this review, our discussion goes beyond the debate on recommendations concerning the best choice between the different available technologies, and their degrees of reproducibility and sensitivity. The available technologies and techniques can be used for different purposes and, as long as all quality controls are rigorously employed, the question is how to maximise the generation of robust, reproducible data on steroid hormones and their crucial roles in human fetal development and subsequent functions.


Assuntos
Feto/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Gônadas/metabolismo , Pesquisa , Feminino , Humanos , Imunoensaio , Masculino , Espectrometria de Massas , Ovário/metabolismo , Ovário/ultraestrutura , Pesquisa/tendências , Desenvolvimento Sexual/genética , Testículo/metabolismo , Testículo/ultraestrutura
8.
J Pediatr Urol ; 17(4): 583-584, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34284957

RESUMO

INTRODUCTION: Ovotesticular disorder of sex development (OTD) is a rare condition. There's a lack of literature addressing gonad-sparing surgery for OTD. OBJECTIVE: Report the laparoscopic partial gonadectomy technique - gonad-sparing surgery - in an 11-year-old child, 46, XX karyotype with OTD with atypical genitalia. MATERIAL AND METHODS: After a complete diagnostic evaluation the patient underwent feminizing genitoplasty followed by laparoscopic partial gonadectomy (gonad-sparing surgery). The patient was positioned on supine position and Trendelenburg. One 5 mm port was placed on the umbilicus and two 3 mm ports in both flanks. A gonadal wedge biopsy was performed to achieve histopathological confirmation before resection. The testicular component of the ovotestis is clearly identified based on macroscopic aspects, and resected with laparoscopic scissors and limited use of electrocautery. DISCUSSION: This case was classified as bipolar or terminal ovotestis. At the 5-month follow-up, the patient attained menarche. No adverse outcomes have been recorded. Postoperative third year follow-up hormone evaluation revealed a= female pattern characteristic and ultrasound demonstraed uterine volume increase, as well as bilateral ovarian tissue development with follicles. CONCLUSIONS: Gonad-sparing procedure is feasible and desirable whenever possible, especially in 46, XX patients with female sex of rearing, since it preserves the fertility potential. The risk of malignancy must be monitored.


Assuntos
Transtornos do Desenvolvimento Sexual , Laparoscopia , Transtornos Ovotesticulares do Desenvolvimento Sexual , Criança , Feminino , Gônadas , Humanos , Transtornos Ovotesticulares do Desenvolvimento Sexual/diagnóstico , Transtornos Ovotesticulares do Desenvolvimento Sexual/cirurgia , Desenvolvimento Sexual
10.
Cell Death Dis ; 12(7): 653, 2021 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-34175894

RESUMO

In female mammals, the proliferation, apoptosis, and estradiol-17ß (E2) secretion of granulosa cells (GCs) have come to decide the fate of follicles. DNA methylation and RSPO2 gene of Wnt signaling pathway have been reported to involve in the survival of GCs and follicular development. However, the molecular mechanisms for how DNA methylation regulates the expression of RSPO2 and participates in the follicular development are not clear. In this study, we found that the mRNA and protein levels of RSPO2 significantly increased during follicular development, but the DNA methylation level of RSPO2 promoter decreased gradually. Inhibition of DNA methylation or DNMT1 knockdown could decrease the methylation level of CpG island (CGI) in RSPO2 promoter and upregulate the expression level of RSPO2 in porcine GCs. The hypomethylation of -758/-749 and -563/-553 regions in RSPO2 promoter facilitated the occupancy of transcription factor E2F1 and promoted the transcriptional activity of RSPO2. Moreover, RSPO2 promoted the proliferation of GCs with increasing the expression level of PCNA, CDK1, and CCND1 and promoted the E2 secretion of GCs with increasing the expression level of CYP19A1 and HSD17B1 and inhibited the apoptosis of GCs with decreasing the expression level of Caspase3, cleaved Caspase3, cleaved Caspase8, cleaved Caspase9, cleaved PARP, and BAX. In addition, RSPO2 knockdown promoted the apoptosis of GCs, blocked the development of follicles, and delayed the onset of puberty with decreasing the expression level of Wnt signaling pathway-related genes (LGR4 and CTNNB1) in vivo. Taken together, the hypomethylation of -758/-749 and -563/-553 regions in RSPO2 promoter facilitated the occupancy of E2F1 and enhanced the transcription of RSPO2, which further promoted the proliferation and E2 secretion of GCs, inhibited the apoptosis of GCs, and ultimately ameliorated the development of follicles through Wnt signaling pathway. This study will provide useful information for further exploration on DNA-methylation-mediated RSPO2 pathway during follicular development.


Assuntos
Metilação de DNA , Epigênese Genética , Folículo Ovariano/metabolismo , Trombospondinas/metabolismo , Animais , Apoptose , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células , Células Cultivadas , Ilhas de CpG , Estradiol/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Camundongos Endogâmicos C57BL , Regiões Promotoras Genéticas , Desenvolvimento Sexual , Sus scrofa , Trombospondinas/genética , Ativação Transcricional , Via de Sinalização Wnt
11.
Orphanet J Rare Dis ; 16(1): 268, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34112222

RESUMO

BACKGROUND: Dozens of genes are involved in 46, XY differences in sex development (DSD). Notably, about 3/4 of patients cannot make a clear etiology diagnosis and single gene variant identified cannot fully explain the clinical heterogeneity of 46, XY DSD. MATERIALS AND METHODS: We conducted a systematic clinical analysis of a 46, XY DSD patient, and applied whole-exome sequencing for the genetic analysis of this pedigree. The identified variants were analyzed by bioinformatic analysis and in vitro studies were performed in human embryonic kidney 293T (HEK-293T) cells which were transiently transfected with wild type or variant NR5A1 and MAP3K1 plasmid. Furthermore, protein production of SRY-box transcription factor 9 (SOX9) was analyzed in cell lysates. RESULTS: A novel NR5A1 variant (c.929A > C, p. His310Pro) and a rare MAP3K1 variant (c.2282T > C, p. Ile761Thr) were identified in the proband, whereas the proband's mother and sister who only carry rare MAP3K1 variant have remained phenotypically healthy to the present. These two variants were predicted to be pathogenic by bioinformatic analysis. In vitro, NR5A1 variant decreased the SOX9 production by 82.11% compared to wild type NR5A1, while MAP3K1 variant had little effect on the SOX9 production compared to wild type MAP3K1. Compared to wild type NR5A1 transfection, the SOX9 production of cells transfected with both wild type plasmids decreased by about 17.40%. Compared to variant NR5A1 transfection, the SOX9 production of cells transfected with both variant plasmids increased by the 36.64%. CONCLUSIONS: Our findings suggested the novel compound variants of NR5A1 and MAP3K1 can alter the expression of SOX9 and ultimately lead to abnormality of sex development.


Assuntos
Transtorno 46,XY do Desenvolvimento Sexual , MAP Quinase Quinase Quinase 1/genética , Fator Esteroidogênico 1/genética , Humanos , Mutação , Linhagem , Desenvolvimento Sexual , Sequenciamento Completo do Exoma
13.
Nat Rev Genet ; 22(9): 588-602, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34083777

RESUMO

Despite being collectively among the most frequent congenital developmental conditions worldwide, differences of sex development (DSD) lack recognition and research funding. As a result, what constitutes optimal management remains uncertain. Identification of the individual conditions under the DSD umbrella is challenging and molecular genetic diagnosis is frequently not achieved, which has psychosocial and health-related repercussions for patients and their families. New genomic approaches have the potential to resolve this impasse through better detection of protein-coding variants and ascertainment of under-recognized aetiology, such as mosaic, structural, non-coding or epigenetic variants. Ultimately, it is hoped that better outcomes data, improved understanding of the molecular causes and greater public awareness will bring an end to the stigma often associated with DSD.


Assuntos
Transtornos do Desenvolvimento Sexual/diagnóstico , Genômica/métodos , Pesquisa Interdisciplinar/métodos , Mutação , Patologia Molecular/métodos , Equipe de Assistência ao Paciente/tendências , Desenvolvimento Sexual , Transtornos do Desenvolvimento Sexual/genética , Humanos
14.
Endocrine ; 73(3): 723-733, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34021489

RESUMO

PURPOSE: To define, benchmark, and publicize elements of quality care (i.e., "good practices") for pediatric patients with disorders/differences of sex development (DSD). METHODS: Principles of quality care were identified by literature review; consensus exists for 11 good practices and adherence was evaluated through online survey of 21 North American clinical sites. RESULTS: Strong uptake was observed for many practices, particularly specialty participation (n ≥ 17 of 21 sites for most core specialties); point of contact (n = 18); expertise in gender dysphoria/dissatisfaction (n = 20); and DSD-specific continuing medical education (n = 18). Greater variability was apparent for frequency of peer support referrals (n = 12 universally practiced); standardized questionnaires for routine assessment of psychosocial adaptation (n = 13) and gender development (n = 10); consistently clarifying patient/family values in decision-making (n = 15); genital exam protocols that exclude trainee education as primary reason (n = 15); and internal patient-tracking efforts (n = 5-10 of 20 sites). CONCLUSION: This study employed a novel approach to designate DSD good practices and identified areas of consistency and variation in these DSD clinical practices. Good practice benchmarking facilitates quality assessment within and across sites, promotes continuous improvement, and empowers stakeholders in locating and delivering high quality care.


Assuntos
Transtornos do Desenvolvimento Sexual , Disforia de Gênero , Criança , Transtornos do Desenvolvimento Sexual/terapia , Humanos , Desenvolvimento Sexual , Inquéritos e Questionários
15.
Biomed Res Int ; 2021: 8893467, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34036105

RESUMO

Chromosomal abnormalities are the main genetic risk factor associated with reproductive and sexual development disorders (DSD). The goal of this study is to retrospectively evaluate the frequency of chromosomal aberrations in Moroccan subjects with problems of procreation or sexual ambiguity. A total of 1005 individuals, including 170 infertile couples, underwent cytogenetic analysis in the Cytogenetic Laboratory of the Pasteur Institute of Morocco. Heparinized blood samples were processed according to the standard karyotype method. A total (81.5%) of the patients studied had a normal karyotype, while the remaining (18.5%) patients had an abnormal karyotype. Female patients had more chromosomal abnormalities (52%) than male patients (48%). These chromosomal aberrations included 154 cases (83%) of sex chromosomal abnormalities, the most common being Turner's syndrome and Klinefelter's syndrome, and 31 cases (17%) had autosomal aberrations, especially chromosome 9 reversal (inv(9)(p12;q13)). The present data shows that among 170 couples, 10.6% had chromosomal abnormalities mainly involved in the occurrence of recurrent miscarriages. Genotype-phenotype correlations could not be made, and therefore, studies using more resolutive molecular biology techniques would be desirable.


Assuntos
Aberrações Cromossômicas , Predisposição Genética para Doença/genética , Desenvolvimento Sexual/genética , Transtornos Sexuais e da Identidade de Gênero/genética , Aborto Habitual/genética , Adolescente , Adulto , Criança , Pré-Escolar , Transtornos Cromossômicos/epidemiologia , Transtornos Cromossômicos/genética , Citogenética , Feminino , Humanos , Lactente , Recém-Nascido , Infertilidade/genética , Cariótipo , Cariotipagem , Síndrome de Klinefelter/epidemiologia , Síndrome de Klinefelter/genética , Masculino , Pessoa de Meia-Idade , Marrocos , Estudos Retrospectivos , Transtornos Sexuais e da Identidade de Gênero/epidemiologia , Translocação Genética/genética , Síndrome de Turner/epidemiologia , Síndrome de Turner/genética , Adulto Jovem
16.
Toxicol Appl Pharmacol ; 422: 115556, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33932463

RESUMO

Many researchers have studied the relationship between lead (Pb) and testis injury, but the underlying mechanisms are still unknown. The participation of long non-coding RNAs (lncRNAs) in biological processes has been proposed. To comprehensively gain insight into the molecular toxicity of Pb, expression patterns are analysed through RNA sequencing (RNA-seq) in male mice treated with 200 mg/L of Pb through the drinking water for 90 days at the onset of puberty. A total of 614 differentially expressed (DE) lncRNAs were included (p ≤ 0.05 and fold change ≥2), of which 288 were up-regulated, and 326 were down-regulated. A total of 2295 DE mRNAs (p ≤ 0.05 and fold change ≥2), including 1202 up-regulated and 1093 down-regulated ones, were found in the testes of Pb-exposed group. Functional analysis results showed that several lncRNAs might be implicated in the bio-pathway of mitogen-activated protein kinase (MAPK) signaling pathway. Finally, seven pairs of lncRNA-mRNA co-expression were established in mice testes and confirmed by RT-qPCR. Moreover, the DE genes were also altered in Sertoli cells. Therefore, our research might be helpful for future exploring the effects of Pb exposure on lncRNA in testis, as well as its function.


Assuntos
Compostos Organometálicos/toxicidade , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Testículo/efeitos dos fármacos , Transcrição Genética/efeitos dos fármacos , Animais , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Estudo de Associação Genômica Ampla , Masculino , Camundongos Endogâmicos ICR , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Células de Sertoli/ultraestrutura , Desenvolvimento Sexual , Transdução de Sinais , Testículo/metabolismo , Testículo/ultraestrutura
17.
Endocrinology ; 162(7)2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33963381

RESUMO

The WNT family of proteins is crucial in numerous developmental pathways and tissue homeostasis. WNT4, in particular, is uniquely implicated in the development of the female phenotype in the fetus, and in the maintenance of müllerian and reproductive tissues. WNT4 dysfunction or dysregulation can drive sex-reversal syndromes, highlighting the key role of WNT4 in sex determination. WNT4 is also critical in gynecologic pathologies later in life, including several cancers, uterine fibroids, endometriosis, and infertility. The role of WNT4 in normal decidualization, implantation, and gestation is being increasingly appreciated, while aberrant activation of WNT4 signaling is being linked both to gynecologic and breast cancers. Notably, single-nucleotide polymorphisms (SNPs) at the WNT4 gene locus are strongly associated with these pathologies and may functionally link estrogen and estrogen receptor signaling to upregulation and activation of WNT4 signaling. Importantly, in each of these developmental and disease states, WNT4 gene expression and downstream WNT4 signaling are regulated and executed by myriad tissue-specific pathways. Here, we review the roles of WNT4 in women's health with a focus on sex development, and gynecologic and breast pathologies, and our understanding of how WNT4 signaling is controlled in these contexts. Defining WNT4 functions provides a unique opportunity to link sex-specific signaling pathways to women's health and disease.


Assuntos
Doenças dos Genitais Femininos , Genitália Feminina , Proteína Wnt4/fisiologia , Saúde da Mulher , Animais , Neoplasias da Mama/genética , Feminino , Doenças dos Genitais Femininos/genética , Humanos , Glândulas Mamárias Humanas/fisiologia , Camundongos , Mutação , Polimorfismo de Nucleotídeo Único/genética , Gravidez , Diferenciação Sexual/fisiologia , Desenvolvimento Sexual/fisiologia , Útero/fisiologia , Proteína Wnt4/genética
18.
Nat Commun ; 12(1): 2395, 2021 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-33888695

RESUMO

The infraorder Brachyura (true or short-tailed crabs) represents a successful group of marine invertebrates yet with limited genomic resources. Here we report a chromosome-anchored reference genome and transcriptomes of the Chinese mitten crab Eriocheir sinensis, a catadromous crab and invasive species with wide environmental tolerance, strong osmoregulatory capacity and high fertility. We show the expansion of specific gene families in the crab, including F-ATPase, which enhances our knowledge on the adaptive plasticity of this successful invasive species. Our analysis of spatio-temporal transcriptomes and the genome of E. sinensis and other decapods shows that brachyurization development is associated with down-regulation of Hox genes at the megalopa stage when tail shortening occurs. A better understanding of the molecular mechanism regulating sexual development is achieved by integrated analysis of multiple omics. These genomic resources significantly expand the gene repertoire of Brachyura, and provide insights into the biology of this group, and Crustacea in general.


Assuntos
Adaptação Fisiológica/genética , Braquiúros/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Genoma/genética , Animais , Aquicultura , Mapeamento Cromossômico , Feminino , Fertilidade/genética , Perfilação da Expressão Gênica , Genes Homeobox/genética , Genômica , Espécies Introduzidas , Estágios do Ciclo de Vida/genética , Masculino , Família Multigênica/genética , Osmorregulação/genética , Desenvolvimento Sexual/genética , Análise Espaço-Temporal , Sequenciamento Completo do Genoma
19.
J Pediatr Urol ; 17(3): 372-377, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33663998

RESUMO

INTRODUCTION: Disorders/differences of sex development (DSD) is a medical term used to encompass patients born with congenital conditions that lead to atypical development of the genitalia and reproductive structures. OBJECTIVE: To evaluate the factual accuracy of shared articles from popular social media platforms regarding the California State Bill, SB-201, Treatment or Intervention: Sex Characteristics of a Minor. DESIGN: We used the BuzzSumo© search engine to analyze the terms "SB 201", "intersex," "DSD," and "surgery ban" for worldwide social media engagement (Facebook, Twitter, Pinterest, and Reedit) one month before and after bill introduction on January 31, 2019, and final hearing on January 13, 2020. Articles were categorized based on source, opinion of the author, accuracy of scientific information, use of term intersex versus disorder/difference of sex development (DSD), definition of intersex, advocacy group quoted, reference to surgical "gender assignment," mention of negative consequences of the bill/other banned surgeries, the definition of medical necessity, parental rights, psychosocial concerns, and photographic content. RESULTS: Twenty unique articles with peak activity were analyzed. Eighteen were from news and two from editorial web sources. All mentioned SB-201.50% were classified as one-sided, meaning both arguments for and against were not presented. 60% of articles were perpetuating selected information correlating with the author's opinion. 65% of articles were misleading in terms of factual accuracy. All articles used the term intersex. 20% of articles used scientific terms such as atypical genitalia (2), DSD (2), and born with variations of sex characteristics (1). A urologist was quoted in 45% of articles, while 75% quoted intersex advocacy groups. 55% of articles referred to the surgeries as "gender normalizing," and 75% referred to "assigning gender". Three articles mentioned other non-DSD surgeries that SB-201 would ban in addition to any that "normalize appearance." 45% (9) included any definition of medical necessity, the most common being inability to urinate (7), which is incompatible with post-natal viability. DISCUSSION: Our study demonstrates that some of the most disseminated information on social media surrounding the introduction and hearing of SB-201 that did not include input from the medical community, perpetuated selected information, and lacked appropriate factual content. CONCLUSION: Misinformation in the media can be harmful to patients and the general public. This study highlights the need for balanced and accurate reporting on medical topics that can have emotional and political consequences when speaking to broader audiences.


Assuntos
Transtornos do Desenvolvimento Sexual , Mídias Sociais , Identidade de Gênero , Humanos , Caracteres Sexuais , Desenvolvimento Sexual
20.
J Pediatr Urol ; 17(3): 338-345, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33691983

RESUMO

Issues and concerns regarding surgery of the sexual-reproductive anatomy during infancy and early childhood are discussed using four actual examples. A case of a 46, XX infant with 21 hydroxylase deficiency congenital adrenal hyperplasia (CAH) with atypical (ambiguous) genitalia is discussed regarding timing and potential harms and benefits of surgery. We present the perspective of balancing the child's rights to bodily autonomy and right to an open future versus parents' decision making authority regarding what they perceive as their child's future best interests. The second case is a newborn with complete androgen insensitivity syndrome and we discuss the harms, benefits and timing of gonadectomy. The third case examines the physical and psychological impact of penile shaft hypospadias, raising the question of whether surgery is justified to prevent what may or may not be considered a permanent disability. The fourth case involves an adult woman with classic CAH, born with a urogenital sinus and clitoromegaly, who never had genital surgery and is now requesting vaginoplasty, but not clitoral reduction. The primary message of this article, as the previous articles in this series, is to encourage patient-family centered care that individualizes treatment guided by shared decision making.


Assuntos
Hiperplasia Suprarrenal Congênita , Transtornos do Desenvolvimento Sexual , Hiperplasia Suprarrenal Congênita/cirurgia , Adulto , Criança , Pré-Escolar , Transtornos do Desenvolvimento Sexual/cirurgia , Feminino , Genitália Feminina , Humanos , Lactente , Recém-Nascido , Masculino , Desenvolvimento Sexual , Procedimentos Cirúrgicos Urogenitais
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