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1.
Elife ; 102021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34647888

RESUMO

The fungus Aspergillus nidulans produces secondary metabolites during sexual development to protect itself from predators.


Assuntos
Aspergillus nidulans , Regulação Fúngica da Expressão Gênica , Aspergillus nidulans/genética , Desenvolvimento Sexual
2.
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
3.
Sci Rep ; 11(1): 16546, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34400657

RESUMO

We examined whether heterosexual individuals' self-reported sexual orientation could be influenced experimentally by manipulating their knowledge of the nature of sexual orientation. In Study 1 (180 university students, 66% female) participants read summaries describing evidence for sexual orientation existing on a continuum versus discrete categories or a control manipulation, and in Study 2 (460 participants in a nationally representative Qualtrics panel, 50% female) additionally read summaries describing sexual orientation as fluid versus stable across the life-course. After reading summaries, participants answered various questions about their sexual orientation. In Study 1, political moderates and progressives (but not conservatives) who read the continuous manipulation subsequently reported being less exclusively heterosexual, and regardless of political alignment, participants reported less certainty about their sexual orientation, relative to controls. In Study 2, after exposure to fluid or continuous manipulations heterosexual participants were up to five times more likely than controls to rate themselves as non-exclusively heterosexual. Additionally, those in the continuous condition reported less certainty about their sexual orientation and were more willing to engage in future same-sex sexual experiences, than those in the control condition. These results suggest that non-traditional theories of sexual orientation can lead heterosexuals to embrace less exclusive heterosexual orientations.


Assuntos
Heterossexualidade/psicologia , Comunicação Persuasiva , Educação Sexual , Comportamento Sexual/psicologia , Adolescente , Adulto , Cultura , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Psicológicos , New South Wales , Política , Autoimagem , Sexismo , Desenvolvimento Sexual , Incerteza , Adulto Jovem
4.
Semin Pediatr Surg ; 30(4): 151078, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34412885

RESUMO

Differences/disorders of sex development (DSD) are a heterogeneous group of congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical. Patients usually present during the newborn period but occasionally some cases remain unrecognized until later in infancy or even adolescence. Genital appearance, psychosocial support, sociocultural background, gender identity development, and genetic and biochemical analysis in addition to ethical and legal implications need to be considered when deciding on the appropriate treatment strategy. Surgeons are important members of the multidisciplinary expert teams involved in the initial approach and long-term follow-up. Surgical care of DSD patients is one of the main challenges. Recommendations regarding the opportunity and timing of surgical procedures are still under discussion. Surgical procedures are aimed to reduce urologic problems, prevent the risk of gonadal germ-cell cancer, and facilitate sexual function and reproduction. Providing its excellent visualization, access to pelvic structures and less postoperative adhesion MIS has been an important tool in the diagnosis and treatment of DSD. The role of MIS will be summarized in: 1) Gonadal biopsy / gonadectomy 2) Treatment of urogenital sinus/vaginoplasty 3) Vaginal Replacement 4) Resection / treatment of Mullerian structures.


Assuntos
Transtornos do Desenvolvimento Sexual , Neoplasias Embrionárias de Células Germinativas , Transtornos do Desenvolvimento Sexual/diagnóstico , Transtornos do Desenvolvimento Sexual/cirurgia , Feminino , Identidade de Gênero , Humanos , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos , Desenvolvimento Sexual
5.
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
6.
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
7.
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
8.
Probl Endokrinol (Mosk) ; 67(3): 73-77, 2021 06 07.
Artigo em Russo | MEDLINE | ID: mdl-34297505

RESUMO

Mutations in the gene DHH are an extremely rare cause of disorders of sex development 46,XY (DSD,46XY). The article describes the clinical cases of two unrelated patients with gonadal dysgenesis 46,XY with female phenotype. By using a next generation sequencing method, in both cases the same biallelic variant substitution c. 419T>G in the DHH gene was revealed. Taking into account the data on the role of DHH in the formation of the nervous system, the diagnosis of minifascicular polyneuropathy at the preclinical stage was confirmed in both cases. These cases demonstrate the value of using NGS, which allows simultaneous analysis of a wide range of candidate genes in DSD and the diagnosis of comorbidities before the development of the clinical picture. These are the first descriptions of patients with mutations in the DHH gene in the Russian population.


Assuntos
Disgenesia Gonadal 46 XY , Proteínas Hedgehog , Feminino , Disgenesia Gonadal 46 XY/diagnóstico , Proteínas Hedgehog/genética , Humanos , Mutação , Desenvolvimento Sexual , Transdução de Sinais
9.
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
10.
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
11.
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
12.
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
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.
Sci Rep ; 11(1): 12882, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34145300

RESUMO

The monitoring of anthropogenic chemicals in the aquatic environment including their potential effects on aquatic organisms, is important for protecting life under water, a key sustainable development goal. In parallel with monitoring the concentrations of chemicals of concern, sentinel species are often used to investigate the biological effects of contaminants. Among these, bivalve molluscs such as mussels are filter-feeding and sessile, hence an excellent model system for measuring localized pollution. This study investigates the relationship between the metabolic state of the blue mussel (Mytilus edulis) and its physiology in different environments. We developed a computational model based on a reference site (relatively unpolluted) and integrated seasonal dynamics of metabolite relative concentrations with key physiological indicators and environmental parameters. The analysis of the model revealed that changes in metabolite levels during an annual cycle are influenced by water temperature and are linked to gonadal development. This work supports the importance of data-driven biology and its potential in environmental monitoring.


Assuntos
Biomarcadores , Meio Ambiente , Gônadas/embriologia , Gônadas/metabolismo , Metaboloma , Mytilus edulis/fisiologia , Desenvolvimento Sexual , Animais , Biologia Computacional/métodos , Metabolômica/métodos , Modelos Teóricos , Mytilus edulis/embriologia , Estações do Ano , Fatores Sexuais , Desenvolvimento Sexual/genética
16.
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
18.
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
19.
Clin Endocrinol (Oxf) ; 95(6): 818-840, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34031907

RESUMO

It is paramount that any child or adolescent with a suspected difference or disorder of sex development (DSD) is assessed by an experienced clinician with adequate knowledge about the range of conditions associated with DSD and is discussed with the regional DSD service. In most cases, the paediatric endocrinologist within this service acts as the first point of contact but involvement of the regional multidisciplinary service will also ensure prompt access to specialist psychology and nursing care. The underlying pathophysiology of DSD and the process of delineating this should be discussed with the parents and affected young person with all diagnostic tests undertaken in a timely fashion. Finally, for rare conditions such as these, it is imperative that clinical experience is shared through national and international clinical and research collaborations.


Assuntos
Transtornos do Desenvolvimento Sexual , Endocrinologia , Adolescente , Criança , Transtornos do Desenvolvimento Sexual/diagnóstico , Humanos , Pais , Desenvolvimento Sexual , Reino Unido
20.
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
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