RESUMO
BACKGROUND: Splenogonadal fusion (SGF) is a rare congenital malformation in which the spleen is abnormally connected to the gonads or to the mesonephric derivatives. There is no obvious causality between SGF and testicular neoplasm. However, cryptorchidism, which is a well-known risk factor of testicular germ cell tumors, are the most frequent malformations associated with SGF. To our knowledge, there are only four reported cases of SGF associated with testicular neoplasm so far. Herein, we reported a patient of this condition, and briefly reviewed the related literature. CASE PRESENTATION: A 48-year-old man was diagnosed with bilateral cryptorchidism 30 years prior, and only underwent a right orchiopexy for the left testicle could not be explored during the operation. At that time, doctors failed to realize the possibility of SGF due to the lack of sufficient knowledge of this condition. This time, the patient was treated for a left abdomen mass that was diagnosed as stage III metastatic seminoma. Then, a right orchiectomy, robot-assisted laparoscopic left retroperitoneal tumor resection, and left retroperitoneal lymph node dissection was performed after four cycles of BEP (bleomycin + etoposide + cisplatin) systemic chemotherapy in our center. The final diagnosis of SGF was made by postoperative pathology. The patient was re-examined in our center at 3 months and 6 months after the operation, and no obvious abnormalities were found. CONCLUSIONS: Surgeons should always bear in mind the possibility of association between bilateral cryptorchidism and splenogonadal fusion to avoid malignant transformation caused by delayed treatment.
Assuntos
Criptorquidismo , Gônadas , Seminoma , Baço , Humanos , Criptorquidismo/cirurgia , Masculino , Pessoa de Meia-Idade , Seminoma/patologia , Seminoma/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica , Orquiectomia , Esplenopatias , Neoplasias Testiculares/patologia , Gônadas/anormalidades , Baço/anormalidades , Resultado do TratamentoRESUMO
Disorders of sexual development (DSD) refers to a group of diseases that links the mismatch between an individual's genetic and gonadal development and its phenotype. Ovotesticular DSD (true hermaphroditism) is one such disease, in which both male and female gonads are present. A 15-year-old boy with a history of surgery for non-palpable testis was examined due to bilateral gynecomastia and known gonosomal mosaic of Klinefelter syndrome. The external genital was matured as male and, in the left half of the scrotum, there was a testicle of normal size. Despite uncertain resistance on the right side, however, the right testis was not palpable. Revision of the right groin revealed a surprising finding in the form of an ovary with a dilated fallopian tube, both of which were completely removed. Surgical revision of the left testis with biopsy was performed. The surgery was completed with a bilateral mastectomy. The postoperative course was uncomplicated, and the boy is content and fully integrated into his peer group. True hermaphroditism is a rare type of DSD. In the case described, DSD was not exhibited until puberty, after an examination for gynecomastia. The case also confirms the necessity of clarification and long-term follow-up of patients with unclear findings during surgery for non-palpable testis. Diagnostic laparoscopy is clearly indicated in these situations.
Assuntos
Transtornos Ovotesticulares do Desenvolvimento Sexual/cirurgia , Adolescente , Genitália/anormalidades , Gônadas/anormalidades , Ginecomastia , Humanos , Laparoscopia , Masculino , FenótipoRESUMO
BACKGROUND: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is defined as incomplete development of Müllerian structures (uterus, fallopian tubes, proximal vagina) in an otherwise phenotypic female individual. MRKH syndrome typically presents in adolescence with primary amenorrhea, but has been diagnosed in younger patients who present with other associated abnormalities, most commonly renal and skeletal. CASE: Here we describe a 46,XX female infant with prenatally diagnosed renal anomalies who was found to have bilateral inguinal ovarian hernias at 1 month of age. Imaging of the genitourinary system revealed absence of the uterus and proximal vagina, consistent with MRKH syndrome. SUMMARY AND CONCLUSIONS: This case highlights the importance of a thorough physical examination and an interdisciplinary team evaluation of infants with genitourinary anomalies, particularly when there is concern for differences in sexual development.
Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/diagnóstico , Anormalidades Congênitas/diagnóstico , Gônadas/diagnóstico por imagem , Ductos Paramesonéfricos/anormalidades , Diagnóstico Diferencial , Feminino , Gônadas/anormalidades , Humanos , Recém-Nascido , PalpaçãoRESUMO
Splenogonadal fusion (SGF) is a rare congenital malformation, which can be of a continuous or discontinuous type. It is characterized by splenic tissue fused with gonadal tissue. Because it lacks characteristic features, very few cases of SGF have been diagnosed preoperatively. Herein, we present a case with left side SGF who was diagnosed by Tc-nanocolloid spleen scintigraphy.
Assuntos
Neoplasias Abdominais/diagnóstico , Gônadas/anormalidades , Canal Inguinal , Baço/anormalidades , Criança , Diagnóstico Diferencial , Gônadas/diagnóstico por imagem , Humanos , Cintilografia , Baço/diagnóstico por imagemRESUMO
CONTEXT: The reproductive axis is controlled by a network of gonadotropin-releasing hormone (GnRH) neurons born in the primitive nose that migrate to the hypothalamus alongside axons of the olfactory system. The observation that congenital anosmia (inability to smell) is often associated with GnRH deficiency in humans led to the prevailing view that GnRH neurons depend on olfactory structures to reach the brain, but this hypothesis has not been confirmed. OBJECTIVE: The objective of this work is to determine the potential for normal reproductive function in the setting of completely absent internal and external olfactory structures. METHODS: We conducted comprehensive phenotyping studies in 11 patients with congenital arhinia. These studies were augmented by review of medical records and study questionnaires in another 40 international patients. RESULTS: All male patients demonstrated clinical and/or biochemical signs of GnRH deficiency, and the 5 men studied in person had no luteinizing hormone (LH) pulses, suggesting absent GnRH activity. The 6 women studied in person also had apulsatile LH profiles, yet 3 had spontaneous breast development and 2 women (studied from afar) had normal breast development and menstrual cycles, suggesting a fully intact reproductive axis. Administration of pulsatile GnRH to 2 GnRH-deficient patients revealed normal pituitary responsiveness but gonadal failure in the male patient. CONCLUSIONS: Patients with arhinia teach us that the GnRH neuron, a key gatekeeper of the reproductive axis, is associated with but may not depend on olfactory structures for normal migration and function, and more broadly, illustrate the power of extreme human phenotypes in answering fundamental questions about human embryology.
Assuntos
Hormônio Liberador de Gonadotropina/metabolismo , Neurônios/fisiologia , Nariz/anormalidades , Transtornos do Olfato/congênito , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/metabolismo , Anormalidades Múltiplas/patologia , Anormalidades Múltiplas/fisiopatologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina/deficiência , Gônadas/anormalidades , Gônadas/patologia , Humanos , Hipogonadismo/genética , Hipogonadismo/metabolismo , Hipogonadismo/patologia , Hipogonadismo/fisiopatologia , Lactente , Hormônio Luteinizante/sangue , Masculino , Pessoa de Meia-Idade , Neurogênese/fisiologia , Neurônios/metabolismo , Transtornos do Olfato/genética , Transtornos do Olfato/metabolismo , Transtornos do Olfato/fisiopatologia , Condutos Olfatórios/metabolismo , Condutos Olfatórios/patologia , Tamanho do Órgão , Adulto JovemRESUMO
Not required for Clinical Vignette.
Assuntos
Hormônio Adrenocorticotrópico/sangue , Síndrome de Resistência a Andrógenos/diagnóstico , Adulto , Síndrome de Resistência a Andrógenos/sangue , Síndrome de Resistência a Andrógenos/diagnóstico por imagem , Síndrome de Cushing/diagnóstico , Diagnóstico Diferencial , Tubas Uterinas/anormalidades , Feminino , Gônadas/anormalidades , Humanos , Masculino , Útero/anormalidades , Vagina/anormalidadesRESUMO
We present the case of splenogonadal fusion in a 53-year-old male patient assessed by ultrasound and MRI, confirmed by pathologic examination. In addition to B-mode and colour-coded Doppler ultrasound, shear wave elastography and CEUS were performed and are presented in detail. Splenogonadal fusion is a rare congenital anomaly presumably caused by an abnormal attachment of splenic tissue to the gonad during gestation. Diagnosis is challenging for clinicians and in unclear cases splenogonadal fusion might cause unnecessary orchiectomies with benign pathologic results. Ultrasound is the first-line imaging modality in the diagnosis of testicular pathologies. This case report summarizes all available modern ultrasound imagingtechnologies and highlights the possibilities for the diagnosis of splenogonadal fusion.
Assuntos
Meios de Contraste , Gônadas/anormalidades , Gônadas/diagnóstico por imagem , Aumento da Imagem/métodos , Baço/anormalidades , Baço/diagnóstico por imagem , Ultrassonografia/métodos , Técnicas de Imagem por Elasticidade/métodos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Campomelic dysplasia (CD) is a skeletal dysplasia characterized by shortened and bowed long bones, airway instability, the potential for disorders of sexual differentiation (DSD), and Pierre Robin Sequence (PRS) with cleft palate, midface hypoplasia and laryngotrachemomalacia. CD is caused by alterations in the Sex-determining region of the Y chromosome (SRY)-related-box 9 (SOX9), which has important roles in tissue and sexual differentiation. The SOX9 gene and the enhancer regions of SOX9 are located at chromosome 17q24.3. We report a 6-year-old phenotypically female referred to our department because of precocious puberty. The patient was born with Tetralogy of Fallot (TOF) and PRS. Skeletal X-ray examination showed only 11 pairs of ribs and bilateral bowed radiuses. Endocrine evaluations showed that increased levels of serum testosterone, and chromosomal analysis revealed a 46, XY, t(2;17)(p15;q24.2) karyotype. The patient was diagnosed with peripheral precocious puberty caused by over-secretion of testosterone by gonadoblastoma originating from dysgenetic gonads with Y-chromosome-related DSD. Multiple somatic abnormalities and DSD indicated that the patient might have CD. Laparoscopy revealed bilateral dysgenetic gonads, and these were removed in the successive operation to prevent malignant transformation and virilization, caused by dysgenetic gonads with Y chromosomal materials. It is highly suggestive that the chromosomal translocation of 17q 24.2 may cause DSD and multiple somatic abnormalities, including CD, although the identified 17q breakpoint was located outside of known SOX9 enhancer regions. Thus, a hitherto unknown enhancer may be present at 17q24.2. This is the first reported case of CD with a translocation breakpoint at 17q24.2.
Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 2/genética , Gônadas/anormalidades , Translocação Genética , Criança , Endoscopia , Feminino , Hormônios/sangue , HumanosRESUMO
The mammalian brain undergoes sexual differentiation by gonadal hormones during the perinatal critical period. However, the machinery at earlier stages has not been well studied. We found that Ptf1a is expressed in certain neuroepithelial cells and immature neurons around the third ventricle that give rise to various neurons in several hypothalamic nuclei. We show that conditional Ptf1a-deficient mice (Ptf1a cKO) exhibit abnormalities in sex-biased behaviors and reproductive organs in both sexes. Gonadal hormone administration to gonadectomized animals revealed that the abnormal behavior is caused by disorganized sexual development of the knockout brain. Accordingly, expression of sex-biased genes was severely altered in the cKO hypothalamus. In particular, Kiss1, important for sexual differentiation of the brain, was drastically reduced in the cKO hypothalamus, which may contribute to the observed phenotypes in the Ptf1a cKO. These findings suggest that forebrain Ptf1a is one of the earliest regulators for sexual differentiation of the brain.
Assuntos
Prosencéfalo/embriologia , Diferenciação Sexual , Fatores de Transcrição/metabolismo , Animais , Linhagem da Célula , Embrião de Mamíferos/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Gônadas/anormalidades , Hipotálamo/embriologia , Hipotálamo/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Diferenciação Sexual/genética , Comportamento Sexual Animal , Fatores de Transcrição/deficiênciaRESUMO
Studies on reproduction in sea turtles are important due to its life cycle, migratory patterns, high juvenile mortality and environmental impacts. This study aimed to analyse histomorphometrically gonads of C. mydas from the coastline of the Espírito Santo State, Brazil. Ovaries and testicles were collected between 2014 and 2015 from stranded animals. The material was fixed in formalin 10%, assessed macroscopically and processed for histomorphometrical evaluation. Gonads from 34 individuals were evaluated, twenty-four females and ten males. Macroscopic sexual identification presented 100% accuracy confirmed by histology. Sexual dimorphism was observed in one individual, which was considered as adult (CCL=1.023 m). Microscopy of female gonads revealed predominant previtellogenic follicles; oocyte diameter ranged between 161µm and 750µm and a positive correlation between ovarian length, largest oocyte and CCL was found. In males, autolysis was verified in five individuals. Viable testicles revealed predominant spermatogonia, primary spermatocytes and Sertoli cells in the seminiferous tubules and, Leydig cells and fibroblasts in the stroma. There was a positive correlation between tubular diameter and CCL and testicle length and CCL. Maturation of stromal tissue and a positive correlation between tubular lumen and CCL were also observed. Gonad development is proportional to individual growth.(AU)
Estudos em reprodução de tartarugas marinhas são importantes devido ao ciclo de vida, ao padrão migratório, à alta mortalidade juvenil e aos impactos ambientais. Objetivou-se analisar histomorfometricamente gônadas de C. mydas no litoral do Espírito Santo. Foram coletados ovários e testículos dessa espécie, entre 2014 e 2015. O material foi fixado em formol a 10% e avaliado macroscopicamente. Em seguida, foi processado para avaliação histomorfométrica. Foram avaliadas gônadas de 34 indivíduos, 24 fêmeas e 10 machos. Verificaram-se 100% de acurácia na identificação sexual à macroscopia, confirmada pela histologia. Observou-se dimorfismo sexual em um macho, que foi considerado adulto (CCC=1,023m). A microscopia dos ovários revelou folículos pré-vitelogênicos, cujos ovócitos apresentaram diâmetro médio entre 161µm e 750µm. Houve correlação positiva entre comprimento ovariano e diâmetro do maior ovócito e CCC. Nos machos, verificou-se autólise em cinco indivíduos. Os testículos viáveis revelaram espermatogônias, espermatócitos primários e células de Sertoli nos túbulos seminíferos, além de células de Leydig e fibroblastos no estroma. Houve correlação positiva entre diâmetro tubular e CCC e comprimento testicular e CCC. Verificou-se maturação do tecido estromal e correlação positiva entre o diâmetro do lúmen tubular e o CCC. Verifica-se que o desenvolvimento das gônadas é proporcional ao crescimento dos indivíduos.(AU)
Assuntos
Animais , Testículo/crescimento & desenvolvimento , Tartarugas/anatomia & histologia , Gônadas/anormalidades , HistologiaAssuntos
Anormalidades Craniofaciais/patologia , Gônadas/anormalidades , Deformidades Congênitas dos Membros/patologia , Escroto/patologia , Escroto/cirurgia , Baço/anormalidades , Esplenopatias/congênito , Testículo/anormalidades , Criança , Diagnóstico Diferencial , Epididimo/patologia , Gônadas/patologia , Humanos , Masculino , Orquiectomia/métodos , Escroto/diagnóstico por imagem , Baço/patologia , Baço/cirurgia , Esplenopatias/patologia , Esplenopatias/cirurgia , Testículo/patologia , Testículo/cirurgia , Resultado do Tratamento , Ultrassonografia/métodosRESUMO
The role of monogenic mutations in the development of 46,XX testicular/ovotesticular disorders of sex development (DSD) remains speculative. Although mutations in NR5A1 are known to cause 46,XY gonadal dysgenesis and 46,XX ovarian insufficiency, such mutations have not been implicated in testicular development of 46,XX gonads. Here, we identified identical NR5A1 mutations in two unrelated Japanese patients with 46,XX testicular/ovotesticular DSD. The p.Arg92Trp mutation was absent from the clinically normal mothers and from 200 unaffected Japanese individuals. In silico analyses scored p.Arg92Trp as probably pathogenic. In vitro assays demonstrated that compared with wild-type NR5A1, the mutant protein was less sensitive to NR0B1-induced suppression on the SOX9 enhancer element. Other sequence variants found in the patients were unlikely to be associated with the phenotype. The results raise the possibility that specific mutations in NR5A1 underlie testicular development in genetic females.
Assuntos
Transtornos do Desenvolvimento Sexual/diagnóstico , Transtornos do Desenvolvimento Sexual/genética , Cariótipo , Mutação de Sentido Incorreto , Fator Esteroidogênico 1/genética , Testículo/metabolismo , Alelos , Substituição de Aminoácidos , Biomarcadores , Análise Mutacional de DNA , Feminino , Genótipo , Gônadas/anormalidades , Humanos , Lactente , Masculino , Modelos Moleculares , Fenótipo , Conformação Proteica , Fator Esteroidogênico 1/químicaRESUMO
Due to their terrestrial habitats and aquatic reproduction, many amphibians are both very vulnerable and highly suitable bioindicators. The plasticizer bisphenol A (BPA) is one of the most produced chemical substances worldwide, and knowledge on its impacts on humans and animals is mounting. BPA is used for the industrial production of polycarbonate plastics and epoxy resins and found in a multitude of consumer products. Studies on BPA have involved mammals, fish and the fully aquatic anuran model Xenopus laevis. However, our knowledge about the sexual development of non-model, often semi-terrestrial anuran amphibians remains poor. Using a recently developed experimental design, we simultaneously applied BPA to two non-model species (Hyla arborea, Hylidae; Bufo viridis, Bufonidae) and the model X. laevis (Pipidae), compared their genetic and phenotypic sex for detection of sex reversals, and studied sexual development, focusing on anatomical and histological features of gonads. We compared three concentrations of BPA (0.023, 2.28 and 228 µg/L) to control groups in a high-standard flow-through-system, and tested whether conclusions, drawn from the model species, can be extrapolated to non-model anurans. In contrast to previous studies on fish and Xenopus, often involving dosages much higher than most environmental pollution data, we show that BPA causes neither the development of mixed sex nor of sex-reversed individuals (few, seemingly BPA-independent sex reversals) in all focal species. However, environmentally relevant concentrations, as low as 0.023 µg/L, were sufficient to provoke species-specific anatomically and histologically detectable impairments of gonads, and affected morphological traits of metamorphs. As the intensity of these effects differed between the three species, our data imply that BPA diversely affects amphibians with different evolutionary history, sex determination systems and larval ecologies. These results highlight the role of amphibians as a sensitive group that is responsive to environmental pollution.
Assuntos
Anuros/crescimento & desenvolvimento , Compostos Benzidrílicos/toxicidade , Poluição Ambiental/efeitos adversos , Fenóis/toxicidade , Plastificantes/toxicidade , Desenvolvimento Sexual/efeitos dos fármacos , Animais , Tamanho Corporal/efeitos dos fármacos , Bufonidae/crescimento & desenvolvimento , Feminino , Genótipo , Gônadas/anormalidades , Gônadas/efeitos dos fármacos , Gônadas/patologia , Larva/efeitos dos fármacos , Masculino , Reprodução/efeitos dos fármacos , Processos de Determinação Sexual/efeitos dos fármacos , Especificidade da Espécie , Xenopus laevis/crescimento & desenvolvimentoRESUMO
Gonadal differentiation has a determinative influence on sex development in human embryos. Disorders of sexual development (DSD) have been associated with persistent embryonal differentiation stages. Between 1998 and 2015, 139 female patients with various (DSD) underwent operations at the Scientific Center of Obstetrics, Gynaecology and Perynatology in Moscow, Russia. Clinical investigations included karyotyping, ultrasound imaging, hormonal measurement and investigations of gonadal morphology. The male characteristics in the embryo are imposed by testicular hormones. When these are absent or inactive, the fetus may be arrested at between developmental stages, or stay on indifferent stage and become phenotypically female. A systematic analysis of gonadal morphology in DSD patients and a literature review revealed some controversies and led us to formulate a new hypothesis about sex differentiation. Proliferation of the mesonephric system (tubules and corpuscles) in the gonads stimulates the masculinization of gonads to testis. Sustentacular Sertoli cells of the testes are derived from mesonephric excretory tubules, while interstitial Leydig cells are derived from the original mesenchyme of the mesonephros. According of the new hypothesis, the original mesonephric cells (tubules and corpuscles) potentially persist in the ovarian parenchyma. In female gonads, some mesonephric excretory tubules regress and lose the tubular structure, but form ovarian theca interna and externa, becoming analogous to the sustentacular Sertoli cells in the testis. The ovarian interstitial Leydig cells are derived from intertubal mesenchyme of the mesonephros, similar to what occurs in male gonads (testis). Surprisingly, the leading determinative factor in sexual differentiation of the gonads is the mesonephros, represented by the embryonic urinary system.
Assuntos
Transtornos do Desenvolvimento Sexual , Gônadas , Processos de Determinação Sexual , Diferenciação Sexual , Feminino , Gônadas/anormalidades , Gônadas/embriologia , Gônadas/crescimento & desenvolvimento , Gônadas/patologia , Humanos , MasculinoRESUMO
BACKGROUND: Splenogonadal fusion is a rare congenital anomaly which is characterized by fusion formation between the spleen and gonad. METHODS: We report a case of a 14-month boy with spleongonadal fusion-limb deformity syndrome focusing on the importance of awareness of this syndrome. RESULTS: The patient was admitted to our clinic because of a left undescended testis, and preoperative diagnosis was not made. During the operation, "spleen-like" tissue attached to the gonad induced splenogonadal fusion, which was confirmed by laparoscopy. The patient also had a short right femur, hip dysplasia and a syndromic face. CONCLUSION: Splenogonadal fusion anomaly should be considered in the evaluation of undescended testis, especially in patients with facial and limb deformities.
Assuntos
Anormalidades Craniofaciais/complicações , Criptorquidismo/etiologia , Gônadas/anormalidades , Deformidades Congênitas dos Membros/complicações , Baço/anormalidades , Humanos , Lactente , MasculinoRESUMO
This report describes a disorder of the sexual development in a beagle dog resulting in an intersex condition. A 6 mo old beagle was presented for evaluation of a protruding structure from the vulva consistent with an enlarged clitoris. Ultrasonographic examination revealed the presence of both gonadal and uterine structures. Retrograde cystourethrovaginogram showed the presence of an os clitoris and severe vaginal stenosis. Histological studies revealed the presence of bilateral ovotestes and uterus. The gonad had interstitial cells within seminiferous-like tubules lined only with Sertoli cells and abundant interstitial cells among primordial, primary, and secondary follicles. Hormone assays completed before and after gonadohysterectomy showed an elevation in the levels of progesterone and dihydrotestosterone that returned to baseline 3 mo after surgery. Testosterone levels that were within the male reference ranges before surgery decreased to basal levels postsurgically. 17-ß-Estradiol levels showed little variation and values were always within the reference ranges for a male. Cytogenetic analysis showed a normal female karyotype (2n = 78, XX) and polymerase chain reaction analysis revealed the absence of the sex-determining region Y gene. In summary, the dog presented bilateral ovotestes and a 2n = 78, XX chromosomal complement lacking the sex determining region Y gene, consistent with a diagnosis of true hermaphroditism.
Assuntos
Transtornos do Desenvolvimento Sexual/veterinária , Doenças do Cão/diagnóstico , Gônadas/anormalidades , Proteína da Região Y Determinante do Sexo/análise , Animais , DNA/genética , Di-Hidrotestosterona/sangue , Transtornos do Desenvolvimento Sexual/diagnóstico , Transtornos do Desenvolvimento Sexual/patologia , Transtornos do Desenvolvimento Sexual/cirurgia , Doenças do Cão/patologia , Doenças do Cão/cirurgia , Cães , Estradiol/sangue , Feminino , Masculino , Progesterona/sangue , Diferenciação Sexual/genética , Proteína da Região Y Determinante do Sexo/genética , Testosterona/sangueRESUMO
CONTEXT: A disturbed process of gonadal formation and maintenance may result in testicular dysgenesis syndrome or disorders of sex development (DSDs), with an increased germ cell cancer (GCC) risk. Early diagnosis and treatment requires the identification of relevant risk factors and initial pathologic stages. OBJECTIVE: To evaluate current knowledge and novel insights regarding GCC risk in patients with DSDs, with the aim of providing a model for clinical use. EVIDENCE ACQUISITION: A Medline search was conducted to identify all original and review articles assessing the aetiology of GCC, GCC risk in DSD patients, new predictive markers related to GCC, and possible clinical scenarios related to GCC and DSDs. EVIDENCE SYNTHESIS: Embryonic development is controlled by orchestrated patterns of gene and subsequent protein expression. Knowledge of these networks is essential to understand the mechanisms of disturbed development including GCC formation. GCCs are subdivided into seminomas and nonseminomas, and they all arise from embryonic germ cells that have failed to mature appropriately. The precursor is known as carcinoma in situ (also referred to as testicular intratubular neoplasia and intratubular germ cell neoplasia unclassified) in a testicular microenvironment and gonadoblastoma in a dysgenetic/ovarian microenvironment. GCCs mimic embryonic development, resulting in the identification of diagnostic markers (eg, OCT3/4, SRY [sex determining region Y]-box 2 [SOX2], and [sex determining region Y]-box 17 [SOX17]). Novel insights indicate a subtle interplay of specific single nucleotide polymorphisms, environmental factors, and epigenetic aberrations in the aetiology of GCCs. A genvironmental model combining these factors is presented, proposed as a guideline for clinical management by an experienced multidisciplinary team. The goal is individualised treatment including preservation of gonadal function (if possible) and prevention of malignant transformation. CONCLUSIONS: A hypothesis is presented in which combined interactions of epigenetic and environmental parameters affect embryonic gonadal development, resulting in delayed/blocked germ cell maturation that determines the risk for GCC formation. Current and future possibilities for early detection of GCCs in risk populations and follow-up in a clinical setting are discussed. PATIENT SUMMARY: This review analyses current knowledge about the underlying networks that relate to the development of a germ cell cancer in the context of a disorder of sex development. A combined effect of epigenetic and environmental factors is identified in the pathogenesis, and a model is proposed to apply this knowledge to clinical practice.
Assuntos
Biomarcadores Tumorais/sangue , Transtornos do Desenvolvimento Sexual/complicações , Detecção Precoce de Câncer/métodos , Gônadas/anormalidades , Neoplasias Embrionárias de Células Germinativas/sangue , Neoplasias Embrionárias de Células Germinativas/etiologia , Transtornos do Desenvolvimento Sexual/sangue , Feminino , Humanos , Masculino , Fatores de Transcrição de Octâmero/sangue , Fatores de Risco , Proteína da Região Y Determinante do Sexo/sangueAssuntos
Biomarcadores Tumorais/sangue , Transtornos do Desenvolvimento Sexual/complicações , Detecção Precoce de Câncer/métodos , Gônadas/anormalidades , Neoplasias Embrionárias de Células Germinativas/sangue , Neoplasias Embrionárias de Células Germinativas/etiologia , Feminino , Humanos , MasculinoRESUMO
Voluta musica is a dioecious marine gastropod endemic of the South Caribbean. Tributyltin (TBT) and copper (Cu) are potential inducers of imposex, an endocrine disorder by which females develop a penis and/or vas deferens. The goal of this work was to determine the imposex incidence in V. musica populations from Northeastern Peninsula de Araya. For this, we selected three sites (Isla Caribe, Isla Lobos and Bajo Cuspe) and made monthly samplings of 15 snails in each site, during one year, and determined: (1) sizes; (2) sex and imposex incidence and (3) the Relative Penis Length Index (RPLI). We also performed histological analysis of the gonads, and measured TBT and Cu concentrations in sediments from the studied localities. Our results showed that the total number of sampled females affected by imposex was 24.5% at Isla Caribe, 12% at Isla Lobos, and none at Bajo Cuspe. In sediments, Cu was detected mostly in Isla Lobos. The female gonads with imposex did not show any development of male cells in any of the sampled sites. The higher percentage of females with imposex matched with the higher boat traffic locality, and higher TBT level (Isla Caribe). No esterilization was evident in this work, nevertheless, the presence of TBT and Cu in the sediments and females with imposex were considered as a potential threat to V. musica populations in this region. In Venezuela there is no control over this particular issue, possibly because of the lack of information and research in this topic, but certainly, this information will be useful in biodiversity conservation policies.
Assuntos
Transtornos do Desenvolvimento Sexual/veterinária , Gastrópodes/efeitos dos fármacos , Gônadas/efeitos dos fármacos , Compostos de Trialquitina/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Transtornos do Desenvolvimento Sexual/induzido quimicamente , Monitoramento Ambiental , Feminino , Gônadas/anormalidades , Masculino , VenezuelaRESUMO
Voluta musica is a dioecious marine gastropod endemic of the South Caribbean. Tributyltin (TBT) and copper (Cu) are potential inducers of imposex, an endocrine disorder by which females develop a penis and/or vas deferens. The goal of this work was to determine the imposex incidence in V. musica populations from Northeastern Península de Araya. For this, we selected three sites (Isla Caribe, Isla Lobos and Bajo Cuspe) and made monthly samplings of 15 snails in each site, during one year, and determined: (1) sizes; (2) sex and imposex incidence and (3) the Relative Penis Length Index (RPLI). We also performed histological analysis of the gonads, and measured TBT and Cu concentrations in sediments from the studied localities. Our results showed that the total number of sampled females affected by imposex was 24.5% at Isla Caribe, 12% at Isla Lobos, and none at Bajo Cuspe. In sediments, Cu was detected mostly in Isla Lobos. The female gonads with imposex did not show any development of male cells in any of the sampled sites. The higher percentage of females with imposex matched with the higher boat traffic locality, and higher TBT level (Isla Caribe). No esterilization was evident in this work, nevertheless, the presence of TBT and Cu in the sediments and females with imposex were considered as a potential threat to V. musica populations in this region. In Venezuela there is no control over this particular issue, possibly because of the lack of information and research in this topic, but certainly, this information will be useful in biodiversity conservation policies.
Voluta musica es un gasterópodo dioico endémico del Caribe sur. El TBT y el Cu, son potenciales causantes del imposex, fenómeno donde las hembras desarrollan un pene y/o vaso deferente. El objetivo fue determinar la incidencia de imposex en V. musica en el noreste de la Península de Araya. Se seleccionaron tres localidades y se captura-ron mensualmente 15 individuos durante un año para determinar: (1) talla de los individuos; (2) sexo y presencia de imposex; (3) índice Largo Relativo del Pene (RPLI). Se realizó histología de la gónada de los individuos. Se determinó TBT y Cu en el sedimento de cada localidad. En Isla Caribe, el 24.5% de las hembras presentó imposex, y se halló 3.9ngSn/g de TBT; en Isla Lobos, el 12% de las hembras desarrollaron imposex; en Bajo del Cuspe no se observó imposex. Se halló Cu en mayor concentración en Isla Lobos. Las gónadas femeninas con imposex no demos-traron masculinización. El mayor porcentaje de imposex coincide con la localidad de mayor tráfico de embarcacio-nes y con mayor nivel de TBT (Isla Caribe). No se eviden-ció esterilización, sin embargo la presencia de TBT, Cu e imposex son potenciales amenazas para las poblaciones de V. musica en la región. Hasta ahora, en Venezuela no se está tomando ninguna medida de control sobre este tema en particular, posiblemente por la escasez de información y orientación de las investigaciones hacia este tema, pero que sin duda se debería tomar en cuenta en las políticas para la conservación de la biodiversidad.