RESUMEN
All malignant testicular germ cell tumors (TGCT) of adult men are preceded by an in situ stage (CIS) of protracted evolution. The adult CIS is well characterized, but there is debate on the phenotype of infantile CIS, its distinction from delayed maturation of germ cells and prognostic potential. A large series of 43 patients with Disorders of Sex Development (DSD) and dysgenetic testes (90% ranging from neonates to 12 years, mean age 4.7 years), was studied by quantifying dysgenetic features, degree of germ cell abnormalities/atypia (GCA), expression of OCT 3/4 (a pluripotency-undifferentiation marker), germ cell ploidy and evolution to CIS and invasive TGCT. Findings were compared with those of normal testes. The type of gonads present defined three groups of patients: bilateral testes (BT-DSD, n = 21), one testis and one streak gonad (CT-DSD, C for combined, n = 13), and ovarian-testicular combinations (OT-DSD, n = 9). There were 5 boys with infantile CIS, bilateral in 3 (total of 8 infantile CIS) and two patients with adult CIS, bilateral in one (total of 3 adult CIS). Two patients had bilateral seminomas one at 12-17 and the other at 23 years. Histological dysgenesis was significantly higher in CT-DSD (p < 0.05), that had only 1 CIS. The highest frequency of GCA was in BT-DSD (p < 0.05), which coincided with a total of 11CIS + Seminomas. In all patients, aneuploidy was significantly higher (63%) than diploidy (p < 0.02), and GCA were more frequent in aneuploid than in diploid samples (p < 0.02). All CIS and TGCT were OCT 3/4 positive. Finally, there was a significant association between the triad Aneuploidy + GCA + OCT 3/4 positivity and the incidence of CIS (Fisher Exact test p < 0.002, relative risk 7.0). The degree of testicular dysgenesis (derived from abnormal organization of Sertoli cells in fetal testicular cords) is inversely related to the incidence of CIS. Our data demonstrate that the combined use of OCT 3/4 expression, quantification of germ cell abnormalities-atypia and ploidy in dysgenetic testes can satisfactorily identify infantile CIS with high risk of malignant evolution and set it aside from delayed germ cell maturation with lower or nil neoplastic potential.
Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma in Situ/genética , Disgenesia Gonadal/genética , Seminoma/genética , Desarrollo Sexual/genética , Neoplasias Testiculares/genética , Adolescente , Argentina/epidemiología , Carcinoma in Situ/química , Carcinoma in Situ/epidemiología , Carcinoma in Situ/patología , Niño , Preescolar , Femenino , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Disgenesia Gonadal/epidemiología , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Factor 3 de Transcripción de Unión a Octámeros/análisis , Fenotipo , Ploidias , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Seminoma/química , Seminoma/epidemiología , Seminoma/patología , Neoplasias Testiculares/química , Neoplasias Testiculares/epidemiología , Neoplasias Testiculares/patología , Adulto JovenRESUMEN
BACKGROUND: In the present report we analyse the structural and functional features of sperm from a patient with severe asthenoteratozoospermia and failure of cleavage after ICSI. METHODS: Sperm were studied by phase contrast and transmission electron microscopy and microinjected into bovine oocytes to examine aster formation using antibodies against acetylated alpha- and beta-tubulins. RESULTS: Acephalic sperm, headless tails and abnormal alignments of the head-tail junction were observed. Flagella evidenced the features of dysplasia of the fibrous sheath. Bovine oocytes injected with patient's sperm showed male and female pronuclei but a faulty development of microtubules from the sperm-derived centrosome. The first ICSI attempt using conventional sperm selection methods resulted in fertilized two pronuclei zygotes, but no syngamy or cleavage. Three more ICSI attempts were performed, carefully avoiding sperm with obvious anomalies of the connecting piece. Fertilization and cleavage took place in all cycles, and in two of them positive betahCG plasma levels were detected but preclinical abortions ensued. CONCLUSIONS: We propose that the alterations in the head-tail junction and attachment, responsible for the observed sperm phenotype, result from centriolar dysfunctions that cause insufficient sperm aster formation, lack of syngamy and cleavage or defective embryos leading to early abortions.
Asunto(s)
Centriolos/fisiología , Centriolos/ultraestructura , Fase de Segmentación del Huevo/fisiología , Interacciones Espermatozoide-Óvulo/fisiología , Espermatozoides/patología , Espermatozoides/fisiología , Adulto , Animales , Bovinos , Femenino , Humanos , Masculino , Microscopía Electrónica , Inyecciones de Esperma IntracitoplasmáticasRESUMEN
BACKGROUND: Human sperm with structural abnormalities display an increased content of the cellular proteolytic marker peptide, ubiquitin. We investigated whether dysplasia of the fibrous sheath (DFS), a severe structural anomaly found in the sperm of some asthenozoospermic patients, is accompanied by (i) increased ubiquitination of the sperm surface and (ii) by increased ubiquitination of the sperm mitochondria. METHODS AND RESULTS: Five DFS patients and eight fertile donors were studied by immunocytochemistry with anti-ubiquitin antibodies. Increased cross-reactivity of the ubiquitinated mitochondrial epitopes was seen in 32-50% of DFS sperm, but only 2-4.1% of sperm from fertile donors. Sperm surface ubiquitination assessed by sperm-ubiquitin tag immunoassay (SUTI) and immunofluorescence demonstrated an increased sperm ubiquitination in all DFS patients. The average median value of ubiquitin-induced fluorescence in DFS patients was 25.8 counts (range 19.8-37.9), as opposed to 13.4 counts range (9.3-16.6) in fertile men. Sperm with 'stump tails', coiled tails, twin and triplet sperm, and clusters of immature spermatogenic cells were common. CONCLUSIONS: DFS sperm have increased cross-reactivity to anti-ubiquitin antibodies, a finding consistent with the ubiquitination of defective sperm shown in animal models. These results justify the use of ubiquitin-based assays for objective semen analysis in infertile men with heritable defects.
Asunto(s)
Infertilidad Masculina/etiología , Espermatozoides/anomalías , Espermatozoides/metabolismo , Ubiquitina/metabolismo , Membrana Celular/metabolismo , Anomalías Congénitas/metabolismo , Citometría de Flujo , Humanos , Inmunoensayo , Masculino , Microscopía Electrónica , Mitocondrias/metabolismo , Mitocondrias/ultraestructura , Espermatozoides/ultraestructuraRESUMEN
We report on six boys with intratubular Sertoli cell proliferations (ISCPs), studied by routine histologic methods, electron microscopy, and immunohistochemistry of anti-müllerian hormone (AMH), inhibin alpha-subunit, 3beta-hydroxysteroid dehydrogenase (3beta-HSD), proliferative cellular nuclear antigen, and p53, and carefully followed for extended periods with periodic clinical examinations, testicular ultrasonographies, and determinations of serum levels of AMH and inhibin B. Peutz-Jeghers syndrome was found in four of six patients, and gynecomastia occurred in five of six patients. One boy had isosexual pseudoprecocity. ISCPs were observed as multiple foci of seminiferous tubules with large and proliferated Sertoli cells replacing germ cells and limited by the basement membrane. Mitotic figures, atypia, and/or interstitial invasion were not observed. Bilateral ISCPs were the only pathologic finding in three patients (patient nos. 1-3) and were associated with a microscopic tumor that resembled a large-cell calcifying Sertoli cell tumor (LCCSCT) in a fourth patient (patient no. 4). In the two remaining patients (patient nos. 5 and 6) ISCPs and LCCSCT were found in both testes. Ultrastructural examination showed large Sertoli cells, with round nuclei, sparse organelles, and some glycogen. Inhibin alpha-subunit immunolocalization was positive in the five patients in whom it was determined (patient nos. 2-6), AMH was positive in those ISCPs associated with tumors (patient nos. 4-6) and negative in isolated ISCPs (patient nos. 2 and 3); 3beta-HSD and PCNA were variable, and p53 was negative in all ISCPs. Patient nos. 1-4 have been followed for 2-19 years. One of them is currently entering puberty, the other two have already completed puberty and have testes of normal size, and the remaining one is an adult with clinically normal testes and sperm production. None of these patients had evidence of tumor development during follow-up as shown by serial ultrasonographies and serum levels of AMH and inhibin B. Patient nos. 5 and 6 who had bilateral ISCPs and LCCSCT were orchidectomized and evolved for 2-10 years after surgery without tumor recurrence. The prognostic significance of ISCPs, particularly when they are the only pathologic finding in a testicular biopsy, is a matter of controversy. Based on the long normal evolution, we recommend a conservative approach to therapy. The bilateral and multicentric character of ISCPs and their association with Sertoli tumors and Peutz-Jeghers syndrome suggest that they represent either proliferative lesions with tumorigenic potential or the intraepithelial stage in the evolution of some testicular Sertoli cell tumors.
Asunto(s)
Glicoproteínas , Lesiones Precancerosas/patología , Tumor de Células de Sertoli/patología , Células de Sertoli/patología , Neoplasias Testiculares/patología , 3-Hidroxiesteroide Deshidrogenasas/análisis , Adolescente , Hormona Antimülleriana , División Celular , Niño , Estudios de Seguimiento , Inhibidores de Crecimiento/sangre , Humanos , Inhibinas/análisis , Inhibinas/sangre , Masculino , Síndrome de Peutz-Jeghers/patología , Lesiones Precancerosas/sangre , Lesiones Precancerosas/química , Lesiones Precancerosas/diagnóstico por imagen , Antígeno Nuclear de Célula en Proliferación/análisis , Tumor de Células de Sertoli/sangre , Tumor de Células de Sertoli/química , Tumor de Células de Sertoli/diagnóstico por imagen , Células de Sertoli/química , Hormonas Testiculares/sangre , Neoplasias Testiculares/sangre , Neoplasias Testiculares/química , Neoplasias Testiculares/diagnóstico por imagen , Proteína p53 Supresora de Tumor/análisis , UltrasonografíaRESUMEN
Dysplasia of the fibrous sheath (DFS) is an anomaly found in spermatozoa of severe asthenozoospermic patients. Marked hypertrophy and hyperplasia of the fibrous sheath is the common characteristic. Immunocytochemistry allowed us to visualize the distortions and incidence of tail structure abnormalities associated with this phenotype in six patients; four with a complete form and two with an incomplete form of this pathology previously diagnosed and studied by electron microscopy. Microtubules and fibrous sheaths were studied using monoclonal antibodies against alpha-acetylated tubulin and anti-FSC1 (the major protein component of the fibrous sheath). Mitochondrial sheaths were visualized using the mitochondrion-specific vital dye MitoTracker green FM(TM). Phase contrast and fluorescent microscopy of semen samples showed large numbers of spermatozoa with short, rigid, thick and irregular tails. As expected, anomalous and completely distorted fibrous sheaths, severe alterations of the axonemal microtubules and different patterns of mitochondrial sheath configurations were found. While ultrastructural studies of thin sections allow an in-depth knowledge of the internal organization of the sperm tail, fluorescence labelling of selected sperm components affords a unique view of the whole flagellum including topographical relationships of various organelles. The combination of these different approaches is essential for a comprehensive understanding of this particular pathology.
Asunto(s)
Infertilidad Masculina/etiología , Proteínas de Plasma Seminal , Cola del Espermatozoide/ultraestructura , Espermatozoides/anomalías , Acetilación , Adulto , Anticuerpos Monoclonales , Técnica del Anticuerpo Fluorescente , Humanos , Hiperplasia , Hipertrofia , Infertilidad Masculina/patología , Masculino , Microscopía Electrónica , Microscopía Electrónica de Rastreo , Microscopía Fluorescente , Microtúbulos/ultraestructura , Mitocondrias/ultraestructura , Proteínas/análisis , Proteínas/inmunología , Cola del Espermatozoide/patología , Espermatozoides/ultraestructura , Tubulina (Proteína)/análisis , Tubulina (Proteína)/inmunologíaRESUMEN
UNLABELLED: Aldosterone producing adenoma (APA) is a rare but potentially curable form of paediatric hypertension. We report a case of APA in a 9-year-old boy, suspected due to persistent hypokalaemia. Neither BP nor initial laboratory investigations disclosed the diagnosis and the presence of an APA was suggested by functional tests and radiological findings. Histologically, a cortical tumour was found associated with a marked medullary hyperplasia of both chromaffin and ganglion cells. CONCLUSION: This case reinforces the need for further investigations in patients with misleading clinical and laboratory data.
Asunto(s)
Adenoma/complicaciones , Neoplasias de las Glándulas Suprarrenales/complicaciones , Hiperaldosteronismo/etiología , Adenoma/patología , Neoplasias de las Glándulas Suprarrenales/patología , Médula Suprarrenal/patología , Niño , Humanos , Hiperplasia , Hipertensión Renal/etiología , Hipopotasemia/etiología , MasculinoRESUMEN
Postnatal evolution of the testis in most laboratory animals is characterized by the close continuity between neonatal activation and pubertal development. In higher primates, infancy, a long period of variable duration, separates birth from the beginning of puberty. This period has been classically considered as a quiescent phase of testicular development, but is actually characterized by intense, yet inapparent activity. Testicular volume increases vigorously shortly after birth and in early infancy due to the growth in length of seminiferous cords. This longitudinal growth results from active proliferation of infantile Sertoli cells which otherwise display a unique array of functional capabilities (oestrogen and anti-müllerian hormone secretion, increase of FSH receptors and maximal response to FSH). Leydig cells also show recrudescence after birth, possibly determined by an active gonadotrophic-testicular axis which results in increased testosterone secretion of uncertain functional role. This postnatal activation slowly subsides during late infancy when periodic phases of activation of the hypothalamo-pituitary-testicular axis are paralleled by incomplete spermatogenic spurts. The beginning of puberty is marked by the simultaneous reawakening of Leydig cell function and succeeding phases of germ cell differentiation/degeneration which ultimately lead to final spermatogenic maturation. The marked testicular growth in this stage is due to progressive increase at seminiferous tubule diameter. Sertoli cells, which have reached mitotic arrest, develop and differentiate, establishing the seminiferous tubule barrier, fluid secretion and lumen formation, and acquiring cyclic morphological and metabolic variations characteristic of the mature stage. All of these modifications indicate that, far from being quiescent, the testis in primates experiences numerous changes during infancy, and that the potential for pubertal development and normal adult fertility depends on the successful completion of these changes.
Asunto(s)
Testículo/crecimiento & desarrollo , Animales , División Celular , Humanos , Lactante , Células Intersticiales del Testículo/citología , Masculino , Primates , Túbulos Seminíferos/citología , Células de Sertoli/citología , Espermatozoides/citologíaAsunto(s)
Infertilidad Masculina/genética , Oligospermia/genética , Espermatozoides/patología , Humanos , Infertilidad Masculina/patología , Masculino , Oligospermia/patología , Cabeza del Espermatozoide/patología , Cabeza del Espermatozoide/ultraestructura , Cola del Espermatozoide/patología , Cola del Espermatozoide/ultraestructura , Espermatozoides/ultraestructuraRESUMEN
OBJECTIVE: To reassess endometrial morphological criteria of normality identifying the best morphological and molecular "implantation window" indicators in normal women. DESIGN: Prospective clinical study. SETTING: Assisted reproductive unit. PATIENT(S): Fourteen healthy volunteers. INTERVENTION(S): Blood sampling for LH, E(2), and progesterone (P4) determinations. Daily vaginal ultrasounds. Two endometrial biopsies per volunteer, 7 days apart, during luteal phase. MAIN OUTCOME MEASURE(S): Endometrial dating, pinopodes formation, immunohistochemical determination of integrins (alphavbeta3, alpha4beta1), leukemia inhibitory factor (LIF), interleukin-1 receptor type I (IL-1R tI), mouse ascites Golgi (MAG), the transmembrane mucin (MUC-1), and P4 receptor expression. RESULT(S): In 26 of 28 biopsies observers agreed; in two biopsies there was a discrepancy (difference of 72 hours). With use of LH peak, 24 of 26 samples were in phase, and 2 were 3 days behind. Pinopodes appeared on days 20-21 and persisted through day 28 in small groups or larger areas. beta3 Integrin was highly expressed in luminal and glandular epithelium from day 22 through 28; 48 hours thereafter pinopodes appeared. alpha4 Subunit exhibited luminal epithelium reaction positivity on days 22-23 and glands on days 18-23. LIF and IL-1R tI showed weak, erratic expression. MAG antibodies showed luminal epithelium expression up to day 22 and glands up to day 25. MUC-1 showed positivity during the whole luteal phase. P4 receptors were positive through day 20 and at the end of the luteal phase. CONCLUSION(S): The three most cited markers that frame the window of implantation do not correlate in our material. Pinopodes are present from day 20 on; beta3 and alpha4 integrin subunits indicate a window opening on days 22-23.
Asunto(s)
Implantación del Embrión , Endometrio/fisiología , Interleucina-6 , Ciclo Menstrual/fisiología , Adulto , Endometrio/anatomía & histología , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Aparato de Golgi/inmunología , Inhibidores de Crecimiento/metabolismo , Humanos , Inmunohistoquímica/métodos , Integrina alfa4beta1 , Integrinas/metabolismo , Factor Inhibidor de Leucemia , Hormona Luteinizante/sangre , Linfocinas/metabolismo , Microscopía Electrónica de Rastreo , Mucinas/metabolismo , Estudios Prospectivos , Receptores de Interleucina-1/metabolismo , Receptores Tipo I de Interleucina-1 , Receptores Mensajeros de Linfocitos/metabolismo , Receptores de Progesterona/metabolismo , Receptores de Vitronectina/metabolismo , Valores de ReferenciaRESUMEN
Gynecomastia in boys with Peutz-Jeghers syndrome and Sertoli cell tumors of gonadal origin results from increased estrogen production due to increased aromatase activity within the testicular tumor. We present a prepubertal boy with Peutz-Jeghers syndrome, gynecomastia and bilateral neoplastic Sertoli cell proliferation in whom the only abnormal hormonal profile was increased concentration of inhibin B and Pro-alpha C in serum.
Asunto(s)
Ginecomastia/sangre , Inhibinas/sangre , Síndrome de Peutz-Jeghers/sangre , Biopsia , División Celular , Niño , Estradiol/sangre , Estrona/análogos & derivados , Estrona/sangre , Hormona Folículo Estimulante/sangre , Ginecomastia/cirugía , Humanos , Hormona Luteinizante/sangre , Masculino , Tumor de Células de Sertoli/patología , Neoplasias Testiculares/patologíaRESUMEN
AIM: Dysplasia of the fibrous sheath (DFS) is an anomaly found in asthenozoospermic patients with extremely low or absent motility. In order to determine the efficacy of ICSI in these patients, a retrospective analysis of ICSI results in DFS patients has been done. METHODS: Ten ICSI attempts were performed in 6 patients with diagnosis of Dysplasia of the Fibrous Sheath studied by transmission and scanning electron microscopy. RESULTS: In the cases studied, sperm concentration was (29.62 +/- 18.05) x 10(6)/mL, total motility was 1.14 +/- 1.31%. Progressive motility was 0% except for one case with 0.1% . One hundred and three preovulatory oocytes were obtained and 94 metaphase II oocytes were injected. Sixty-nine of them showed two pronuclei (fertilization rate: 73.4%). Forty-nine embryos were obtained and 34 were transferred (mean: 3.4 embryos per transfer). Five pregnancies were diagnosed by beta-hCG plasma level determinations that resulted to be one preclinical abortion, one clinical abortion and three deliveries. Another pregnancy (ongoing) was achieved from a cryopreserved embryo transfer. CONCLUSION: These results showed that ICSI provides a suitable solution for patients suffering from irreversible sperm defects such as DFS. Nevertheless, it is mandatory to inform couples of possible transmission risks to offspring, which are unknown at present. Only when the etiology of this problem is disclosed, it will be possible to assess the real genetic risk.
Asunto(s)
Trastornos de la Motilidad Ciliar , Embarazo/estadística & datos numéricos , Inyecciones de Esperma Intracitoplasmáticas , Espermatozoides , Adulto , Femenino , Humanos , Masculino , Microscopía Electrónica , Estudios RetrospectivosRESUMEN
A series of 10 young sterile men with acephalic spermatozoa or abnormal head-mid-piece attachments is presented. Nine of these patients had 75-100% spermatozoa with minute cephalic ends and 0-25% abnormal head-middle piece attachments. Loose heads ranged between 0-35 for each 100 spermatozoa and normal forms were rare. Two patients were brothers. On ultrastructural examination, the head was generally absent and the middle piece was covered by the plasma membrane. When present, heads implanted at abnormal angles on the middle piece. A testicular biopsy showed abnormal spermiogenesis. The implantation fossa was absent and the flagellar anlage developed independently from the nucleus, resulting in abnormal head-middle piece connections. In one patient azoospermia was induced with testosterone to attempt to increase the normal sperm clone during the rebound phenomenon, but all newly formed spermatozoa were acephalic. In another patient with high numbers of defective head-mid-piece connections, microinjections of spermatozoa resulted in four fertilized oocytes, but syngamy and cleavage did not take place, suggesting an abnormal function of the centrioles. The findings indicate that acephalic spermatozoa arise in the testis as the result of an abnormal neck development during spermiogenesis. The familial incidence and the typical phenotype strongly suggest a genetic origin of the syndrome.
Asunto(s)
Infertilidad Masculina/genética , Infertilidad Masculina/patología , Espermatozoides/anomalías , Adulto , Femenino , Fertilización In Vitro , Humanos , Infertilidad Masculina/terapia , Masculino , Microinyecciones , Microscopía Electrónica , Microscopía Electrónica de Rastreo , Fenotipo , Cabeza del Espermatozoide/ultraestructura , Espermatogénesis , Espermatozoides/ultraestructura , Síndrome , Testículo/patología , Cigoto/patologíaRESUMEN
Antecedentes: El síndrome de insensibilidad a los andrógenos (SIA) es un estadi intersexual que se presenta en pacientes con cariotipo 46XY y testículos bien diferenciados, con genitales exteriores ambiguos o femeninos. Es una variante del pseudohermafroditismo masculino, caracterizada por la insensibilización periférica androgénica completa, por defecto genético del cromosoma X. Los pacientes con SIA han crecido y desarrollado como mujeres debido a la conversión periférica de andrógenos a estrógenos y por falta de receptores androgénicos. Objetivos: Analizar dos casos de SIA en pacientes con constitución cromosónica XY pero fenotípica y socialmente mujeres, cuyos testículos ubicados en el retroperitoneo, fueron extirpados por vía laparoscópica. Población: Se presentan dos pacientes de 16 y 14 años, que consultaron por amenorrea primaria, ambas con buen desarrollo mamario y marcada hipoplasia de genitales externos. Fueron operadas en la primera infancia por hernia inguinal bilateral. Las ecografías mostraban la ausencia o hipoplasia de los genitales internos y la presencia de voluminosos testículos retroperitoneales. Método: Se efectuó un estudio exhaustivo, tanto clínico como hormonal y genético. Confirmado el diagnóstico, se realizó la exéresis gonadal por vía laparoscópica y luego, medicación hormonal sustitutiva. Resultados: Evolución favorable de ambas pacientes con alta sanatorial al día siguiente. El examen histopatológico confirmó el diagnóstico de SIA y el análisis molecular del gen receptor de los andrógenos no demostró la presencia de mutaciones puntuales en los exones estudiados. Conclusiones: Se debe sospechar la presencia de SIA en la post-pubertad y adultez en toda paciente cona amenorrea primaria e histoplasia genital externa, con mamas normales. La exéresis gonadal está indicada por el alto riesgo de malignización. La presencia de testículos en la cavidad abdominal o el retroperitoneo, hace de la técnica laparoscópica el procedimiento de elección. El estudio y tratamiento de esta patología debe ser hecha por un equipo multidisciplinario (AU)
Asunto(s)
Humanos , Adolescente , Masculino , Síndrome de Resistencia Androgénica/cirugía , Trastornos del Desarrollo Sexual/genética , Síndrome de Resistencia Androgénica/fisiopatología , Síndrome de Resistencia Androgénica/tratamiento farmacológico , Amenorrea/etiología , Infertilidad Femenina/etiología , Trastornos del Desarrollo Sexual/genética , Trastornos del Desarrollo Sexual/diagnóstico por imagen , Genitales Femeninos/embriología , Genitales Masculinos/embriología , Homosexualidad/genética , Laparoscopía/métodosRESUMEN
Antecedentes: El síndrome de insensibilidad a los andrógenos (SIA) es un estadi intersexual que se presenta en pacientes con cariotipo 46XY y testículos bien diferenciados, con genitales exteriores ambiguos o femeninos. Es una variante del pseudohermafroditismo masculino, caracterizada por la insensibilización periférica androgénica completa, por defecto genético del cromosoma X. Los pacientes con SIA han crecido y desarrollado como mujeres debido a la conversión periférica de andrógenos a estrógenos y por falta de receptores androgénicos. Objetivos: Analizar dos casos de SIA en pacientes con constitución cromosónica XY pero fenotípica y socialmente mujeres, cuyos testículos ubicados en el retroperitoneo, fueron extirpados por vía laparoscópica. Población: Se presentan dos pacientes de 16 y 14 años, que consultaron por amenorrea primaria, ambas con buen desarrollo mamario y marcada hipoplasia de genitales externos. Fueron operadas en la primera infancia por hernia inguinal bilateral. Las ecografías mostraban la ausencia o hipoplasia de los genitales internos y la presencia de voluminosos testículos retroperitoneales. Método: Se efectuó un estudio exhaustivo, tanto clínico como hormonal y genético. Confirmado el diagnóstico, se realizó la exéresis gonadal por vía laparoscópica y luego, medicación hormonal sustitutiva. Resultados: Evolución favorable de ambas pacientes con alta sanatorial al día siguiente. El examen histopatológico confirmó el diagnóstico de SIA y el análisis molecular del gen receptor de los andrógenos no demostró la presencia de mutaciones puntuales en los exones estudiados. Conclusiones: Se debe sospechar la presencia de SIA en la post-pubertad y adultez en toda paciente cona amenorrea primaria e histoplasia genital externa, con mamas normales. La exéresis gonadal está indicada por el alto riesgo de malignización. La presencia de testículos en la cavidad abdominal o el retroperitoneo, hace de la técnica laparoscópica el procedimiento de elección. El estudio y tratamiento de esta patología debe ser hecha por un equipo multidisciplinario
Asunto(s)
Humanos , Adolescente , Masculino , Trastornos del Desarrollo Sexual/genética , Síndrome de Resistencia Androgénica/cirugía , Amenorrea/etiología , Trastornos del Desarrollo Sexual , Trastornos del Desarrollo Sexual/genética , Síndrome de Resistencia Androgénica/fisiopatología , Síndrome de Resistencia Androgénica/tratamiento farmacológico , Genitales Femeninos/embriología , Genitales Masculinos/embriología , Homosexualidad/genética , Infertilidad Femenina/etiología , Laparoscopía/métodosRESUMEN
Prognostic markers in pediatric adrenal cortical tumors are difficult to define. We determined the ploidy, immunostaining of p53-protein and number of nucleolar organizer regions (AgNORs) in 16 such tumors and related them to clinical outcome, tumor weight (TW) and histologic Weiss' criteria. Eleven females and 5 males aged 0.4 to 15.6 years were followed for 8.7 years; 10 presented Cushing's and 6 virilization syndrome. Diploid (n = 4, x TW = 269 g, range: 17-800 g) and near-diploid tumors (n = 3, x TW = 55 g, range: 20-85 g) had good outcome, Weiss' criteria were 0-7, and p53 reactivity was negative in all. Among the aneuploid tumors (n = 9, x TW = 298 g, range: 7-1000 g), 6 had good outcome, 2 presented metastasis and 1 was lost to follow-up; Weiss' criteria were 2-8 and p53 reactivity was positive in 3 tumors (2 of them of malignant evolution). AgNORs number was not different in cases of good or poor outcome (3.65 +/- 1.9 vs 2.83 +/- 1.1). Our findings indicate that diploid and near-diploid cases had always a good outcome regardless of tumor weight. In aneuploid cases, tumor weights < 100 g had good outcome, while those > 750 g had poor prognosis. Malignant tumors were aneuploid and had reactivity to p53-protein. Good outcome in aneuploid tumors < 100 g is probably due to early treatment. The expression of p53-protein appears as a promising marker of poor prognosis. Weiss' criteria and AgNORs were not useful in the present series.
Asunto(s)
Neoplasias de la Corteza Suprarrenal/genética , Región Organizadora del Nucléolo/ultraestructura , Proteína p53 Supresora de Tumor/análisis , Adolescente , Neoplasias de la Corteza Suprarrenal/química , Neoplasias de la Corteza Suprarrenal/ultraestructura , Aneuploidia , Niño , Preescolar , ADN/análisis , Diploidia , Femenino , Citometría de Flujo , Humanos , Lactante , Masculino , Pronóstico , Tinción con Nitrato de PlataRESUMEN
An ultrastructural study of spermatozoa in a series of 247 severely asthenozoospermic patients disclosed two kinds of anomalies. The first was dysplasia of the fibrous sheath, a primary defect of spermatozoa with hypertrophy and hyperplasia of the fibrous sheath, associated axonemal anomalies, familial incidence and chronic respiratory disease. The patients could be divided into two subgroups: the complete form (all spermatozoa affected) and the incomplete form (alterations in 70-80% spermatozoa). There were no spontaneous or in-vitro fertilization (IVF) pregnancies. Intracytoplasmic sperm injection (ICSI) in six patients resulted in successful fertilizations, but only two pregnancies were obtained. These features configure a phenotype that suggests a genetic origin. The second anomaly was non-specific flagellar anomaly (NSFA), random secondary flagellar alterations affecting variable numbers of spermatozoa, without respiratory disease or familial incidence. 54 men with NSFA were followed for 2-6 years. Of these, 18 achieved conception, either spontaneous or by means of assisted fertilization, followed by 14 pregnancies and 12 live births. Their sperm motility significantly increased during the follow-up period. In the remaining 36 men motility did not change during the follow-up period and there were no fertilizations or pregnancies. We conclude that in severe asthenozoospermia, ultrastructural examination of spermatozoa has an effective prognostic value, identifying two syndromes with very different flagellar alterations and fertility potentials.
Asunto(s)
Flagelos/ultraestructura , Oligospermia/patología , Espermatozoides/patología , Flagelos/patología , Humanos , Masculino , Oligospermia/fisiopatología , Valor Predictivo de las Pruebas , Pronóstico , Espermatozoides/ultraestructuraRESUMEN
The purpose of this study was to evaluate the effects of GnRH-analog (Leuprolide acetate, LA) administration on follicular luteinization in equine chorionic gonadotropin plus human chorionic gonadotropin (eCG + hCG)-superovulated prepubertal treated rats. Results indicate that LA treatment decreases circulating levels of progesterone (P) and P accumulation in collagenase-dispersed ovarian cell cultures, though estradiol (E2) production is increased. These data suggest that cells from the LA group may be less luteinized following gonadotropin treatment. Studies performed on histological ovarian sections after different times of eCG administration showed that LA injections produce lower amounts of corpora lutea and antral follicles, and a greater number of atretic and preantral follicles. The basal and LH-stimulated P and progestagen accumulations are decreased in incubations of corpora lutea isolated from the LA group. In addition, the mitochondrial cholesterol side-chain cleavage (P450SCC) levels in corpora lutea from LA-treated rats are reduced, indicating that the decrease in P production observed is due in part to an alteration in the steroidogenic luteal capability. Immunocytochemical localization of nuclei exhibiting DNA fragmentation by the technique of terminal deoxynucleotidyl transferase end-labeling showed that LA treatment causes an increase in the number of apoptotic cells in preantral and antral follicles at all times studied (1, 2, 4, or 7 days of LA administration). A similar effect, though less pronounced, was observed in corpora lutea. It is concluded that LA treatment produces a failure in the steroidogenic luteal capability and an increase of apoptotic mechanisms in the ovary, producing as a consequence an interference in the follicular recruitment, growth, and luteinization induced by gonadotropins.
Asunto(s)
Apoptosis/fisiología , Fármacos para la Fertilidad Femenina/farmacología , Hormona Liberadora de Gonadotropina/agonistas , Leuprolida/farmacología , Fase Luteínica/fisiología , Folículo Ovárico/fisiología , Animales , Femenino , Hormona Liberadora de Gonadotropina/fisiología , Humanos , Fase Luteínica/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
The present report describes a successful intracytoplasmic sperm injection (ICSI) procedure performed with immotile spermatozoa from a young man with a combination of dysplasia of the fibrous sheath and dynein deficiency, a recently described variant of the immotile cilia syndrome. This methodology provides the only suitable solution for these patients in whom all other assisted fertilization technologies have previously failed, and opens the possibilities for treatment of male infertility due to severe, irreversible sperm defects such as the one reported here.
Asunto(s)
Fertilización In Vitro/métodos , Infertilidad Masculina/etiología , Infertilidad Masculina/terapia , Microinyecciones , Enfermedades Respiratorias/complicaciones , Espermatozoides/anomalías , Adulto , Enfermedad Crónica , Dineínas/deficiencia , Transferencia de Embrión , Femenino , Humanos , Hiperplasia , Hipertrofia , Masculino , Embarazo , Resultado del Embarazo , Cola del Espermatozoide/ultraestructura , Espermatozoides/ultraestructuraRESUMEN
The purpose of this study was to evaluate the developmental changes of the Leydig cells and their precursors during postnatal development in the monkey Cebus apella. Four groups of monkeys were studied: neonatal, infantile, early pubertal and late pubertal. Light microscopy, immunocytochemistry, electron microscopy and stereological studies were performed to determine cytologic and cytochemical characteristics, volume density, absolute volume and cell counts of Leydig cells. In the interstitial tissue two components were recognized: specific interstitium comprising mature and immature Leydig cells and differentiating Leydig cell precursors, and non-specific interstitium including connective tissue and blood vessels. Mature Leydig cells were polygonal with a round, euchromatic nucleus and abundant cytoplasm. Immature Leydig cells were more elongated and the nucleus showed more heterochromatin. Mature and immature Leydig cells showed either a pale- or a dark-stained cytoplasm. Pale Leydig cells showed abundant smooth endoplasmic reticulum (SER), mitochondria with tubular cristae and glycogen granules. The SER of dark Leydig cells consisted of abundant flat cisternae, only few glycogen inclusions and abundant lipid droplets. All Leydig cells were intensely reactive for 3beta-hydrohysteroid dehydrogenase (3beta-HSD). Some peritubular cells acquired nuclear and cytoplasmic characteristics that indicated that they were differentiating to Leydig cells, as evidenced by the strong 3beta-HSD positivity found in scattered elongated cells of the peritubular tissue. Absolute interstitial volume increased from birth to the end of puberty due to an increment in Leydig cells numbers and size. The mature and immature Leydig cell populations showed a different evolution during postnatal development. While immature Leydig cells increased 7-fold from the neonatal to the early pubertal period and increased at a lower rate during puberty, mature Leydig cells remained stable until early puberty and increased significantly during late pubertal development.
Asunto(s)
Cebus/anatomía & histología , Células Intersticiales del Testículo/ultraestructura , Testículo/crecimiento & desarrollo , Animales , Cebus/crecimiento & desarrollo , Recuento de Células , Histocitoquímica , Inmunohistoquímica , Masculino , Microscopía Electrónica , Células Madre/ultraestructura , Testículo/ultraestructuraRESUMEN
BACKGROUND: Controversy exists as to which variable is a reliable predictor of clinical outcome of adrenal cortical tumors in children. METHODS: Twenty patients with adrenal cortical tumors were studied. Tumor weight, histologic features, and percentage of proliferating cell nuclear antigen (PCNA/cyclin) in tumor cells were analyzed to determine the best predictor of clinical outcome. RESULTS: Eleven patients had Cushing's syndrome with virilization and 9 had virilization without Cushing's syndrome. The mean age at diagnosis was 7.1 +/- 5.2 years (range, 0.4-15.6 years). Sixteen patients, with good outcomes have been followed for 10.7 +/- 7.8 years (range, 3-23 years). All but two patients had a tumor weight of less than 100 g (185 g and 800 g, respectively) (mean 47.7 g +/- 46.4 g). Two patients with large tumors (weighing 1000 g and 780 g, respectively) had poor outcomes; 1 died 3 months after surgery with metastasis and the other presented with lung metastasis 18 months after surgery. Histologic features did not correlate with clinical outcome. Overall, PCNA stained cells were 6.96 +/- 8.2% (range, 0-32.5%). PCNA values were significantly lower in tumors of patients with good outcomes (P < 0.002). Within all tumors, we found a weak correlation between tumor weight and PCNA (r = 0.51; P < 0.02), but a better correlation was found between tumor weight and PCNA in patients with Cushing's syndrome (r = 0.70; P < 0.01). Patients with Cushing's syndrome had higher PCNA values than those with virilization syndrome (10.3 +/- 9.6% vs. 2.8 +/- 3.3%; P < 0.03). CONCLUSIONS: Our data show that small tumors (less than 100 g) are associated with good outcome; the two patients with the poorest prognosis had Cushing's syndrome and large tumors (more than 100 g). Histologic features are not adequate predictors of outcome and PCNA may be useful in tumors of patients with Cushing's syndrome, but this parameter should not be used alone. Two patients had virilization syndrome, large tumors (185 g and 800 g, respectively), and good outcomes, which contradicts with the concept that these tumors are usually associated with poor prognosis.