Ethynylestradiol feminizes gene expression partly in testis developing as ovotestis and disrupts asymmetric Müllerian duct development by eliminating asymmetric gene expression in Japanese quail embryos.

In avian embryos, xenoestrogens induce abnormalities in reproductive organs, particularly the testes and Müllerian ducts (MDs). However, the molecular mechanisms remain poorly understood. We investigated the effects of ethynylestradiol (EE2) exposure on gene expression associated with reproductive organ development in Japanese quail embryos. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis revealed that the left testis containing ovary-like tissues following EE2 exposure highly expressed the genes for steroidogenic enzymes (P450scc, P45017α, lyase, and 3ß-HSD) and estrogen receptor-ß, compared to the right testis. No asymmetry was found in these gene expression without EE2. EE2 induced hypertrophy in female MDs and suppressed atrophy in male MDs on both sides. RNA sequencing analysis of female MDs showed 1,366 differentially expressed genes between developing left MD and atrophied right MD in the absence of EE2, and these genes were enriched in Gene Ontology terms related to organogenesis, including cell proliferation, migration and differentiation, and angiogenesis. However, EE2 reduced asymmetrically expressed genes to 21. RT-qPCR analysis indicated that genes promoting cell cycle progression and oncogenesis were more highly expressed in the left MD than in the right MD, but EE2 eliminated such asymmetric gene expression by increasing levels on the right side. EE2-exposed males showed overexpression of these genes in both MDs. This study reveals part of the molecular basis of xenoestrogen-induced abnormalities in avian reproductive organs, where EE2 may partly feminize gene expression in the left testis, developing as the ovotestis, and induce bilateral MD malformation by canceling asymmetric gene expression underlying MD development.

Revisión pictográfica de las anomalías de los conductos de Müller por resonancia magnética / Pictographic review of Müllerian duct anomalies by magnetic resonance imaging

Las anomalías útero-vaginales o müllerianas son un grupo de patologías congénitas que se originan por un defecto del desarrollo, fusión o canalización de los conductos de Müller en la etapa embrionaria, excepcionalmente pueden deberse a una alteración adquirida. La mayoría se diagnostica en forma tardía, como resultado de estudios de infertilidad o complicaciones obstétricas tempranas o tardías. La resonancia magnética (RM) es un examen no invasivo, que no utiliza radiación ionizante, con una alta resolución de contraste, que permite la evaluación multiplanar de las malformaciones müllerianas, permitiendo su aproximación diagnóstica y caracterización, complementando otras técnicas de imágenes como la histerosalpingografía y la ecografía ginecológica. El radiólogo debe estar familiarizado con las alteraciones anatómicas de los genitales femeninos y su representación en RM permitiendo un diagnóstico diferencial apropiado, oportuno y en consecuencia, un tratamiento adecuado. Este artículo describe los hallazgos en este grupo de malformaciones según la clasificación de la American Fertility Society, la más utilizada en la literatura actual.

The uterus-vaginal or Müllerian anomalies are a group of congenital diseases that are caused by a developmental defect, merger or channeling of Müllerian ducts in the embryonic stage, exceptionally may be due to an acquired disorder. Most belatedly diagnosed as a result of studies of infertility or early or late obstetric complications. Magnetic resonance imaging (MRI) is a noninvasive test that does not use ionizing radiation, with high contrast resolution, which allows multiplanar evaluation of Müllerian malformations, allowing its diagnostic approach and characterization, complementing other imaging techniques such as hysterosalpingography and gynecological ultrasound. The radiologist should be familiar with the anatomical abnormalities of the female genitalia and its representation in MRI, allowing an appropriate and timely differential diagnosis, and consequently, an appropriate treatment.

Conduta frente às malformações genitais uterinas: revisão baseada em evidências / Medical care for uterine genital malformations: evidence-based review

Este trabalho de revisão foi idealizado para analisar as malformações dos ductos de Müller, que, devido à sua frequência de 3 a 7,3% na população em geral, justificam uma análise mais profunda do tema. O objetivo foi avaliar, de acordo com a literatura por meio de metodologia adequada? Os aspectos mais relevantes dessas anomalias, com destaque para a etiopatogenia, classificação, diagnóstico e tratamento. Os resultados obtidos nesta revisão apontaram as melhores evidências, até o momento, de como conduzir as mulheres portadoras dessas malformações.

This review paper was organized in order to analyse Müllerian anomalies, because their frequency from 3 to 7,3% in people in general justify a better evaluation about these malformations. The objective of the study was to evaluate, according to literature - by a proper methodology - the main aspects of these malformations, with special attention to etiology, classification, diagnostic and treatment. The results of this review showed the best evidences up till now of how to manage women with these genital malformations.

Müllerian duct anomalies: review of current management / Malformações Müllerianas: revisão da abordagem atual

The aim of this paper was to discuss the embryological aspects of Müllerian duct anomalies and to analyze the current diagnostic methods and therapy. Müllerian anomalies are congenital defects of the female reproductive tract resulting from failure in the development of the Müllerian ducts and their associated structures. Their cause has yet to be fully clarified, and it is currently believed to be multifactorial. Symptoms appear principally during adolescence or early adulthood, and affect the reproductive capacity of these women. When clinically suspected, investigations leading to diagnosis include imaging methods such as hysterosalpingography, ultrasonography and magnetic resonance. The classification of these malformations relates to their embryogenesis, and defines the therapy and prognosis. Müllerian anomalies consist of a wide range of defects that may vary from patient to patient. Therefore, their management must also be individual, taking anatomical and clinical characteristics into consideration, as well as the patient's wishes.

O objetivo deste trabalho foi discutir as malformações müllerianas desde seus aspectos embriológicos, analisando os atuais métodos diagnóstico e terapêuticos. As malformações müllerianas são anomalias congênitas do trato reprodutivo feminino decorrentes de falha do desenvolvimento dos ductos de Müller e estruturas associadas. Sua causa não foi completamente elucidada, acreditando-se, atualmente, que seja multifatorial. Os sintomas se manifestam, principalmente, durante a adolescência e início da vida adulta, e afetam a capacidade reprodutiva dessas mulheres. A partir da suspeita clínica, a investigação diagnóstica inclui métodos de imagem, como a histerosalpingografia, ultrassonografia e ressonância magnética. A classificação das malformações está relacionada à sua embriogênese e direciona a terapêutica e prognóstico. As malformações müllerianas são um grupo amplo de anomalias que variam de paciente para paciente. Portanto, sua abordagem também é individual, devendo-se considerar os aspectos anatômicos, clínicos e o desejo da paciente.

Adenosarcoma de ovario asociado con elevación del antígeno sérico Ca-125: informe de caso y revisión de literatura / Ovarian adenosarcoma with elevated CA125 antigen: case report and literature review

BACKGROUND: Adenosarcomas are rare tumors usually derived from the endometrium. About 50 cases of adenosarcomas of the ovary have been reported. The relationship between adenosarcoma and CA125 has not been described. The authors present a case of adenosarcoma with elevated CA125 because of the unusual presentation of this pathology and also because elevation of the CA125 antigen has not been reported in the literature. CLINICAL CASE: A 42-year-old woman presented for consultation for incidental right ovarian tumor and CA125 of 1100 U/mL. Histology revealed a homologous Müllerian adenosarcoma of the right ovary with sarcomatous overgrowth. CA125 decreased to 16 U/mL after surgery. Sixteen months post-surgery, the patient is disease free and with normal CA125. DISCUSSION: Ovarian adenosarcomas are more aggressive than adenosarcomas of the uterus. Because of the embryological origin, ovarian adenosarcomas are able to produce CA125 antigen, especially in the presence of sarcomatous overgrowth. With these facts, CA125 antigen may be useful as a prognostic factor because it may represent an indirect marker of sarcomatous overgrowth. CONCLUSIONS: CA125 may be useful for follow-up of ovarian adenosarcomas. Elevated CA125 antigen in adenosarcomas of the ovary may be indicative of sarcomatous overgrowth and poor prognosis.

Anomalías mullerianas: revisión / Mullerian anomalias: review

Las anomalías Müllerianas son un grupo heterogéneo de malformaciones que ocurren en formas variadas, como agenesia útero-vaginal, disgenesias, septos vaginales, útero unicorne, didelfo, bicorne, septado y arcuato y con manifestaciones igualmente diversas, como amenorrea primaria, disfunción sexual, dolor y masas pélvicas, endometriosis, hemorragia uterina anormal, infección, aborto recurrente espontáneo, o partos prematuros. Aun así, es posible encontrar cerca de un 50 por ciento de alteraciones uterinas simétricas asintomáticas. Las anomalías Müllerianas sintomáticas ameritan un diagnóstico diferencial juicioso y oportuno y un tratamiento quirúrgico apropiado. En este artículo se revisan las diferentes malformaciones, junto con la etiología, el diagnóstico y las opciones de tratamiento actualmente disponibles, con base en la experiencia del autor en el servicio de Ginecología y Obstetricia del Hospital Militar Central de Bogotá y en la revisión de la literatura.

Drenaje venoso pulmonar anómalo parcial y síndrome de Mayer-Rokitansky-Kuster-Hauser / Partial Anomalous Pulmonary Venous Drainage and Mayer-Rokitansky-Küster-Hauser Syndrome

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Diferenciación sexual: el factor de Jost / Sexual differentiation: the Jost factor

El estudio de la diferenciación sexual de los mamíferos es, sinduda, un ejemplo relevante de proceso epigénetico producido por lainteracción entre genoma y hormonas secretadas por los testículos fetales: la testosterona y la hormona anti-Müllerian. La diferenciación sexual se produce a nivel periférico, en las gónadas y, también, a nivel cerebral, hipotálamico, en dos vertientes: la neuroendocrina y la de conducta sexual. Ambas vertientes del dimorfismo sexual cerebral pueden ser estudiadas en rata. La primera, por la ovulación, o no, que se produce en un ovario trasplantado en la cavidad abdominal de ratas hembras o en machos, los cuales son, ambos, castrados, previamente al nacimiento, y, la segunda, por la postura de lordosis, que presentan las ratas hembras, debidamente diferenciadas sexualmente, frente al macho. Se han localizado las diferentes zonas cerebrales en donde existen receptores para estrógenos. En la diferenciación periférica o gonadal el diferenciador es el testículo fetal que secreta dos hormonas. La testosterona que mantiene y diferencia los canales Wolff en vasos deferentes, epidídimo y vesículas seminales y la hormona anti-Müllerian (AMH) que provoca la regresión de los canales de Müller, todo ello, en el embrión genéticamente macho. En el cual se diferencian, previamente, los testículos en la etapa fetal de desarrollo de gónadas. En el embrión hembra, sin testículos, y consecuentemente sin testosterona ni AMH, los canales de Wolff involucionan y los de Müller, de forma espontánea, se diferencian en útero, trompas de Falopio y parte superior de la vagina. El conocimiento y aclaración de dichas cuestiones pudo establecerse por el descubrimiento, en fetos de conejos, hecho por el Profesor Alfred Jost, en París (1947-50), de la hormona anti-Müllerian (AMH). Actualmente, la AMH se presenta con múltiples funciones, aunque la más fundamental sea la de regresión de los canales Müllerianen los fetos genéticamente masculinos. Esta hormona es, además, un marcador de patologías como las neoplasias ováricas o la anormal esteroidogénesis del ovario y su hallazgo aclara todo el heterogéneo grupo de patologías de intersexualidad gonadal. Se ha clonado su gen y se han preparado sus anticuerpos. Por pertenecer a la familia del TGFβ (factor de crecimiento transformanteβ) cuyos miembros están implicados en procesos neoplásicos está siendo, actualmente, muy estudiada. Tanto sus posibles aplicaciones en terapéutica, como sus funciones en adulto, son aún investigaciones abiertas al futuro (AU)

Sexual differentiation: the Jost factor Sexual differentiation in mammals is a good example of the epigenetic process produced by the interaction between the genome and hormones secreted by the fetal testes: testosterone and anti-Müllerian hormone (AMH).Sexual differentiation takes place in the gonads and brain(hypothalamus) in two branches: neuroendocrine and sexual behavior. Both branches of the cerebral sexual dimorphism can be studied in the rat. The former by the ovulation pattern of an ovary transplanted in the abdominal cavity of male or female rats which are castrated at birth. The latter can be examined by the response of lordosis of female rats with plain sexual differentiation in front ofthe male. The different brain regions containing estrogen receptors have been localized. Fetal testes regulate gonadal differentiation through two hormones; testosterone an anti-Müllerian hormone. Testosterone differentiates Wolff channels in deferent vessels, epididimus and seminal vesicles, and AMH induces the regression of Müller channels in the genetically male embryo, in which testes are previously differentiated in the last fetal stage of gonad development. In the female, with no testosterone or AMH, the Wolff channels undergo involution and those of Müller spontaneously differentiate to uterus, Fallopian trumps and upper part of vagina. The credit for the knowledge of these matters should be given to Prof. Alfred Jost (Paris, 1947-50), who discovered AMH in rabbit fetuses. Currently, AMH has been endowed with many biological functions, the most important being the involution of Müllerian channels in genetically male fetuses. AMH is a biomarker of diseases such as ovarian tumors and abnormal steroid synthesis in ovary and its finding helped explain a heterogeneous number of sexual-related pathologies. AMH gene has been cloned and anti-AMH monoclonal antibodies obtained. Since AMH has been associated with the transforming growth factor beta (TGF-β) family, whose members are involved in cancer processes, its biological functions and potential therapeutic applications are currently and will certainly be subject of intense studies (AU)

A case of bilateral seminoma in the setting of persistent mullerian duct syndrome (letter)

Reportamos el caso de un hombre de 34 años con genotipo 46XY que se presentó con un seminoma testicular bilateral teniendo criptorquidia bilateral y hernia inguinal izquierda. El paciente fue tratado con 5 ciclos de cisplatino/ciclofosfamida seguido de 3000 cGy de radioterapia. Posteriormente el paciente fue sometido a resección de la masa abdominal y de una estructura pélvica no identificada en el momento de la cirugía. El análisis histopatológico de la pieza quirírgica reveló necrosis del seminoma residual y un útero atrófico. Actualmente el paciente se encuentra sin evidencia de enfermedad a 88 meses de seguimiento. Este es el tercer caso informado de un paciente con síndrome de persistencia del conducto mulleriano con seminoma bilateral.

Utero septado con duplicación cervical y tabique vaginal: una malformación rara / Septate uterus with cervical duplication. A rare malformation

Se presentan dos casos de una malformación mulleriana que incluye útero septado con duplicación cervical y tabique vaginal longitudinal total. Existen pocos casos informados previamente en la literatura médica. Se realiza la discución y una revisión de la literatura