RESUMEN
In most cases, male sexual differentiation occurs with SRY gene mediation. However, exceptional genotypes have been identified, as shown in this paper. This was a male adult patient seen at the Servicio de Paternidades, Instituto de Genética, Universidad Nacional de Colombia. The following procedures were carried out: Amelogenin gene and short tandem repeat analyses using human identification commercial kits, conventional karyotype, SRY fluorescent in situ hybridization, PCR analysis for Y chromosome microdeletions, clinical evaluation, and genetic counseling. We present an adult male with unambiguous genitalia, karyotype 46,XX, and an SRY negative and ZFY positive molecular profile. The diagnosis of nonsyndromic 46,XX testicular disorder of sex development (DSD) -a rare genetic condition- was established. Only 20 % of similarly diagnosed patients are SRY negative and exhibit diverse molecular profiles. Until now, available evidence seems to indicate that, even in the absence of SRY, the ZFY factor is involved in male sexual differentiation.
En la mayoría de los casos, la diferenciación sexual masculina ocurre con la participación del gen SRY. Sin embargo, se pueden presentar otros genotipos excepcionales, como en el caso que se presenta en este reporte. Se trata de un paciente adulto de sexo masculino atendido en el Servicio de Paternidades del Instituto de Genética de la Universidad Nacional de Colombia. Se le hicieron los análisis del gen de la amelogenina y de repeticiones cortas en tándem (Short Tandem Repeat, STR) específicas para el gen SRY con estuches comerciales de identificación humana, así como los de cariotipo convencional e hibridación in situ fluorescente del SRY, y el estudio de microdeleciones del cromosoma Y mediante reacción en cadena de la polimerasa (PCR). Se le hizo la evaluación clínica y se le brindó asesoramiento genético. El paciente no presentaba ambigüedad genital, su cariotipo era 46 XX, y el perfil molecular era negativo para el gen SRY y positivo para el ZFY. Se le diagnosticó un trastorno de diferenciación sexual 46 XX testicular no sindrómico, una rara condición genética. Solo el 20 % de los pacientes con este diagnóstico son negativos para SRY y exhiben perfiles moleculares diversos. La información disponible parece indicar que el ZFY está relacionado con la diferenciación sexual masculina, aún en ausencia del gen SRY.
Asunto(s)
Trastornos del Desarrollo Sexual 46, XX/diagnóstico , Trastornos del Desarrollo Sexual 46, XX/genética , Genes sry , Genitales Masculinos/anatomía & histología , Adulto , Amelogenina/análisis , Deleción Cromosómica , Cromosomas Humanos Y/genética , Electroforesis Capilar , Genotipo , Humanos , Hibridación Fluorescente in Situ , Infertilidad Masculina/diagnóstico , Infertilidad Masculina/genética , Cariotipificación , Factores de Transcripción de Tipo Kruppel/análisis , Factores de Transcripción de Tipo Kruppel/genética , Masculino , Repeticiones de Microsatélite , Técnicas de Amplificación de Ácido Nucleico , Linaje , Reacción en Cadena de la Polimerasa/métodos , Aberraciones Cromosómicas Sexuales , Trastornos de los Cromosomas Sexuales del Desarrollo Sexual/diagnóstico , Trastornos de los Cromosomas Sexuales del Desarrollo Sexual/genéticaRESUMEN
Spermatogenesis is a process in which differentiated cells are produced and the adult stem cell population-known as spermatogonial stem cells (SSCs)-is continuously replenished. However, the molecular mechanisms underlying these processes are not fully understood in the canine species. We addressed this in this study by analysing the expression of specific markers in spermatogonia of seminiferous tubules of canine testes. SSCs at different stages of reproductive development (prepubertal and adult) were examined by immunohistochemistry and flow cytometry. Glial cell-derived neurotrophic factor family receptor alpha-1 (GFRA1), deleted in azoospermia-like (DAZL) and promyelocytic leukaemia zinc finger (PLZF) were expressed in SSCs, while stimulated by retinoic acid gene 8 (STRA8) was detected only in undifferentiated spermatogonia in prepubertal testis and differentiated spermatogonia and spermatocytes in adult canine. Octamer-binding transcription factor 4 (OCT4) showed an expression pattern, and the levels did not differ between the groups examined. However, C-kit expression varied as a function of reproductive developmental stage. Our results demonstrate that these proteins play critical roles in the self-renewal and differentiation of SSCs and can serve as markers to identify canine spermatogonia at specific stages of development.
Asunto(s)
Perros/fisiología , Proteínas/análisis , Espermatogénesis/fisiología , Espermatogonias/química , Células Madre Germinales Adultas/química , Animales , Biomarcadores/análisis , Proteína 1 Delecionada en la Azoospermia , Citometría de Flujo/veterinaria , Receptores del Factor Neurotrófico Derivado de la Línea Celular Glial/análisis , Inmunohistoquímica/veterinaria , Factores de Transcripción de Tipo Kruppel/análisis , Masculino , Proteínas de Unión al ARN/análisis , Túbulos Seminíferos/citología , Maduración Sexual , Espermatogonias/crecimiento & desarrolloRESUMEN
Regulation of cell renewal in the periodontium is a critical cell function that has not been clarified. Sonic hedgehog (Shh) is a secreted signaling molecule that plays a key role during development and adult tissue homeostasis. In the present study, we have analyzed the role played by Shh in human periodontal ligament stem cell (HPLSC) proliferation. HPLSC were isolated with anti-STRO-1 antibodies. Shh increased the expression of GLI1 and PTC-1 and selectively stimulated cell proliferation in STRO-1(+) derived from adult periodontal ligament. Shh components were localized to primary cilia in STRO-1(+) cells after Shh stimulation. STRO-1(+) also expressed Shh, suggesting an autocrine-regulated phenomenon. Thus, we propose that Shh plays a critical role in the regulation of cell proliferation in STRO-1(+)/HPLSC.