Sexual determination and differentiation during embryonic and fetal development of New Zealand rabbit females / Determinación y diferenciación sexual durante el desarrollo embrionario y fetal de conejos hembras de Nueva Zelanda

The aim of this study was to know the embryonic and fetal development of the female rabbit genital system (Oryctolagus cuniculus), describing its main phases and the moment of sexual differentiation. Eleven pregnant New Zealand female rabbits were used in different gestational phases. The day of coitus was determined as day 0. For each stage a minimum of two animals was considered. The samples were obtained every two days from the ninth day post-coitus (dpc) until the 28th dpc. The gestational period was divided in two: animals with undifferentiated sex (group 1) and animals with differentiated sex (group 2). The ages of embryos and fetuses were estimated through the crown-rump method. Subsequently, embryos and fetuses were dissected, fixed and processed to be embedded in paraffin (Histosec). The histological analysis was performed on sections stained with hematoxylin and eosin. Immunohistochemical analysis to determine sexual differentiation was performed on samples from the 16th, 18th and 28th dpc. Desert Hedgehog (Dhh) and Indian Hedgehog (Ihh) primary antibodies, respectively, were used to identify cells of the male and female germinal epithelium. The immunohistochemical results showed that at the 16th dpc, female sexual differentiation was evident, since positive expression of the Ihh protein was observed. Sexual differentiation was obtained through histological analysis on the 18th dpc and through anatomical observation of the external genitalia on the 24th dpc. Knowing the characteristics of the embryonic and fetal development of the female rabbit genital system as well as the moment of sexual differentiation make it possible to establish bases for future research that address the physiology and pathology of these organs. Thus, any alteration in the chain of events of sexual determination and differentiation must search for an explanation from the knowledge of the possible normal mechanisms affected.

El objetivo de esta investigación fue conocer el desarrollo embrionario y fetal del sistema genital femenino de conejo (Oryctolagus cuniculus), describiendo sus principales fases y el momento de la diferenciación sexual. Se utilizaron 11 conejos hembras gestantes neozelandesas, en diferentes fases gestacionales. El día del coito se determinó como día 0. Para cada etapa fue considerado un mínimos de dos animales. Las muestras fueron obtenidas cada dos días, a partir del noveno día post-coito (dpc) hasta el 28 dpc. El periodo gestacional fue dividido en dos: animales con sexo indiferenciado (grupo 1) y, animales con sexo diferenciado (grupo 2). Las edades de los embriones y los fetos fueron estimadas a través del método de crown-rump. Posteriormente, embriones y fetos fueron disecados, fijados y procesados para su inclusión en parafina (Histosec). El análisis histológico se realizó en secciones teñidas con Hematoxilina y Eosina. El análisis inmunohistoquímico para determinar la diferenciación sexual fue realizado en muestras de 16, 18 y 28 dpc. Para identificar células del epitelio germinativo masculino y feminino se utilizaron los anticuerpos primarios Desert Hedgehog (Dhh) e Indian Hedgehog (Ihh), respectivamente. Los resultados inmunohistoquímicos mostraron que a los 16 dpc se evidenció diferenciación sexual femenina, ya que se observó expresión positiva de la proteína Ihh. La diferenciación sexual, a través del análisis histológico fue obtenida a los 18 dpc y a través de la observación anatómica de los genitales externos a los 24 dpc. Conocer las características del desarrollo embrionario y fetal del sistema genital femenino de conejo, así como, el momento de la diferenciación sexual, permiten sentar bases para futuras investigaciones que aborden la fisiología y patología de estos órganos. Así, cualquier alteración en la cadena de eventos de la determinación y diferenciación sexual deberá buscar una explicación a partir del conocimiento de los posibles mecanismos normales afectados.

Dimorfismo sexual humano / Human sexual dimorphism

En esta publicación se describen las diferencias dimórficas sexuales observadas en los seres humanos. Ademas se intenta explicar el origen de las mismas, que se considera preferentemente hormonal en los rasgos que definen la masculinidad morfológica y psicológica. En las mujeres los rasgos dimórficos son posiblemente de origen genético, no dependientes de los determinantes hormonales. Desde allí se puede suponer que el biotipo humano original es la mujer lo que quizás tenga eventual significado biológico.

Sexual dismorphic differences observed in human are described in this publication. Attemps to explain the origin of the observed differences suggest hormonal responsability in the determination of the tracts that defines the morphological and psychological masculinity. Those tracts that characterizes morphological and psychological feminity are supposed genetics or constitutional, but no hormonal in its origin. From these observations we may support that the woman is the original human biotype maybe with a biological significance.

Left ventricular mass in normal children and its correlation with weight, height and body surface area / Masa ventricular izquierda en niños normales y su correlación con el peso, altura y área de superficie corporal

Echocardiographic measurement of left ventricular mass (LVM) is being used for the diagnosis of left ventricular hypertrophy in children with various cardiovascular diseases. The purposes of this study was to establish normal values of LVM according to weight, height and body surface area (BSA) in children and to determine the sex differences. We evaluated 208 children (143 males and 65 females), aged 1 day to 14 years who had no cardiovascular disease. The end-diastolic left ventricular internal dimension (LVIDd), end-diastolic left ventricular posterior wall thickness (LVPWd) and end-diastolic interventricular septum (IVSd) values were determined by M-mode echocardiographic examination. By using these values, left ventricular mass was calculated. The difference between LVIDd, LVPWd and LVM values of boys and girls were not statistically significant . We observed statistically significant differences between the sexes relative to IVSd and LVM/BSA values. The left ventricular mass and its components presented a good correlation with age, weight, height and BSA. The study let us know the lower and upper limits of cardiac dimensions and LVM obtained by echocardiography in normal Turkish children according to BSA. Also, as the LVM/BSA values show gender difference in children, sex should be taken in consideration while evaluating the left ventricular hypertrophy.

La medición ecocardiográfica de la masa ventricular izquierda (LVM) se utiliza para el diagnóstico de la hipertrofia ventricular izquierda en los niños con diversas enfermedades cardiovasculares. Los objetivos de este estudio fueron establecer los valores normales de MVI en función del peso, altura y área de superficie corporal (BSA) en niños y determinar las diferencias entre sexos. Se evaluaron 208 niños (143 varones y 65 mujeres), con edades entre 1 día a 14 años de edad que presentaban enfermedades cardiovasculares. Se determinaron los valores interno al final del diástole ventricular izquierdo (LVIDd), el espesor de la pared posterior (LVPWd) y el tabique interventricular (IVSd) mediante el examen ecocardiográfico en modo M. Utilizando estos valores, fue calculada la masa ventricular izquierda. Las diferencias de los valores LVIDd, LVPWd LVM entre niños y niñas no fueron estadísticamente significativas. Observamos diferencias estadísticamente significativas entre los sexos en relación con los valores IVSd y LVM/BSA. La masa ventricular izquierda y sus componentes presentaron una buena correlación con la edad, peso, altura y BSA. Este estudio nos permitió conocer los límites superior e inferior de las dimensiones cardíacas, junto a la LVM obtenidas mediante ecocardiografía en niños turcos normales de acuerdo con el BSA. Además, como los valores LVM/BSA muestran diferencias entre sexos en los niños, el sexo se debería tomar en consideración al evaluar la hipertrofia ventricular izquierda.

O discurso biomédico e o da construção social na pesquisa sobre intersexualidade / The biomedical discourse and the social construction in research on intersexuality

A intersexualidade se define pela existência de desequilíbrio entre os fatores responsáveis pela determinação do sexo: o indivíduo apresenta caracteres tanto masculinos quanto femininos. A ambiguidade sexual apresenta-se como demarcador da condição de intersexo. Esta revisão de literatura analisou artigos científicos de medicina, psicologia, ciências sociais e direito/ativismo político, acessados através de bancos e portais eletrônicos. As publicações foram analisadas segundo contexto, área/disciplina, tipo de artigo, conteúdo e metodologia do estudo. Os resultados apontaram que os artigos médicos consideraram a intersexualidade como doença crônica, enfatizando as características endocrinológicas e genéticas, efeitos físicos e psicológicos da cirurgia genital. Os artigos de psicologia destacaram aspectos da sexualidade, identidade e orientação sexual. As ciências sociais realizaram uma crítica à visão bipolar do gênero, ressaltando o processo de designação sexual dos intersexuais. Os artigos do campo do direito/ativismo político priorizaram temas como: estigmas sociais, implicações das cirurgias da genitália e mobilização social em prol do direito à saúde. Em relação às metodologias dos estudos, as pesquisas médicas utilizaram predominantemente a abordagem comparativa; os estudos em psicologia utilizaram abordagens qualitativas com entrevistas semi-estruturadas ou questionários; em ciências sociais, os artigos priorizaram pesquisas etnográficas e revisões de literatura; no campo do direito/ativismo político, foram destacadas narrativas e estudos de caso. As narrativas das famílias só foram encontradas em uma publicação, pertencente ao campo da psicologia. Na maioria dos artigos, o conceito de intersexualidade aparece claramente atravessado pelo discurso biomédico. O legado da biomedicina atua diretamente na construção de significados sobre o corpo e gênero.

The intersex is defined by the existence of imbalance between the factors responsible for sex determination: the individual holds both male and female characteristics. The sexual ambiguity presents the path of intersex condition. This literature review examined papers in medicine, psychology, law and social/political activism, accessed through electronic databases and portals. The publications were analyzed according to context, area/discipline, article type, content and methodology of the study. The results showed that the medical articles considered intersexuality as a chronic disease, with emphasis on endocrine and genetic characteristics, physical and psychological effects of genital surgery. Articles of psychology emphasized aspects of sexuality, identity and sexual orientation. Social sciences conducted a critique of the bipolar view of gender, emphasizing the process of designation of sex intersex. The articles of the field of law/political activism prioritized issues such as social stigmas, implications of surgery of the genitalia and social mobilization for the right to health. Regarding the methodology of the studies, medical research has predominantly used a comparative approach, the studies in psychology have used qualitative approaches with semi-structured interviews or questionnaires, social sciences articles prioritized ethnographic research and literature reviews, the field of law/political activism highlighted narratives and case studies. The narratives of families have only been found in a publication, belonging to the field of psychology. In most papers, the concept of intersexuality appears clearly crossed the biomedical discourse. The legacy of biomedicine acts directly on the construction of meanings about the body and gender.

O pediatra frente a uma criança com ambigüidade genital: [revisão] / The role of the pediatrician in the management of children with genital ambiguities: [review]

OBJETIVO: Apresentar os critérios diagnósticos de ambigüidade genital, a conduta médica inicial e a postura esperada do pediatra. FONTES DOS DADOS: Revisão de literatura científica por meio de artigos publicados no MEDLINE nos idiomas inglês e português, no período de 1990 a 2007 e na faixa etária pediátrica. SÍNTESE DOS DADOS: O pediatra tem papel fundamental na avaliação da ambigüidade genital, cujo objetivo é obter diagnóstico etiológico preciso no menor tempo possível para definição do sexo e estabelecimento dos procedimentos terapêuticos. Há critérios diagnósticos específicos, porém, de modo geral, uma genitália é ambígua sempre que houver dificuldade para se atribuir o sexo à criança. O pediatra deve informar à família que a definição do sexo dependerá de investigação laboratorial minuciosa, feita preferencialmente por equipe interdisciplinar em serviço terciário. O cariótipo 46,XX ou 46,XY não é suficiente para definir o sexo de criação, porém esse exame é fundamental para direcionar a investigação. Quando não houver gônadas palpáveis, a primeira hipótese deve ser hiperplasia adrenal congênita. Entre as outras causas, estão insensibilidade parcial a andrógenos, deficiência da enzima 5alfa-redutase, disgenesia gonadal parcial e hermafroditismo. A família deve receber apoio e informações durante todo o processo de avaliação, e sua participação é fundamental na decisão sobre o sexo de criação. CONCLUSÕES: Embora casos de ambigüidade genital sejam relativamente raros para o pediatra, este deve estar informado sobre o tema e a conduta adequada a tomar, pois freqüentemente será o responsável pela orientação inicial da família e pela ligação entre esta e a equipe interdisciplinar.

OBJECTIVE: To present the diagnostic criteria of genital ambiguity, the initial medical management and the attitude expected of pediatricians. SOURCES: Review of the scientific literature in the form of articles indexed on MEDLINE, in English and Portuguese, published between 1990 and 2007 and dealing with the pediatric age group. SUMMARY OF THE FINDINGS: Pediatricians have a fundamental role to play in the assessment of genital ambiguity, the purpose of which is to arrive at an etiologic diagnosis in the shortest possible time in order to define the patient's sex and plan treatment. There are specific diagnostic criteria, but, in general, genitalia are ambiguous whenever there is difficulty in attributing gender to a child. The pediatrician should inform the patient's family that assignment of their child's sex will depend upon detailed laboratory investigations, preferably carried out by a multidisciplinary team at a tertiary service. The 46,XX or 46,XY karyotypes are not alone sufficient to define the gender of rearing, although the test is fundamental to guide the investigation. When there are no palpable gonads, the first hypothesis should be congenital adrenal hyperplasia. Other causes included partial androgen insensitivity, 5alpha-reductase deficiency, partial gonadal dysgenesis and hermaphroditism. The family should be provided with support and information throughout the assessment process, and their participation is fundamental in the decision of which gender to rear the child in. CONCLUSIONS: Although cases of genital ambiguity are relatively rare for pediatricians, they should be well-informed on the subject and the correct management of these conditions, since they will often be responsible for the initial guidance that families receive and for maintaining contact between them and the multidisciplinary team.

Trastornos de la diferenciación sexual: presentación de un caso de genitales ambiguos y revisión del tema / Inconveniences of the sexual differentiation: presentation of a case of ambiguous genitals and review of the theme

Los trastornos de la diferenciación sexual constituyen un grupo complejo de entidades y síndromes. El término estados intersexuales hace referencia a aquellos recién nacidos que presentan genitales ambiguos, esto es, sin evidencia clara sobre sexo asignable. Su frecuencia en nuestro medio es relativamente escasa. Se presenta el caso de un recién nacido en el que, en el examen físico, presenta micropenisomía y escroto bífido. La fusión labioescrotal está alterada con rodetes separados que semejan labios mayores y una estructura que remeda un introito vaginal. En el estudio ultrasonográfico se descartó la presencia de útero y ovarios y se constató la presencia de testículos en canal inguinal. La cromatina sexual de células en interfase de la mucosa oral reveló la presencia de 0 de cuerpo Barr y el estudio cromosómico mostró un cariotipo masculino normal (46, XY), por lo que se interpreta el caso como un pseudohermafroditismo masculino. Se realiza una revisión de los trastornos de la diferenciación sexual.

Sexual differentiation disorders constitute a group of complex syndromes and entities. The term intersexual states makes reference to those newborns that present with ambiguos genitalia, that is, without any clear evidence of defined sex. Intersexuality may be classified as masculine and femenine pseudohermaphroditism and true hermaphroditism, which is caused by incomplete sexual differentiation in the male or virilization in the female. This disorder is relatively rare in our context, though knowledge increases more and more about it thanks to the development of molecular biology and the discovered involvement of genes in the normal sexual differentiation process. This article presented the case of a newborn whose dysmorphological exam at birth indicated positive findings in external genitalia such as micropenis and bifid scrotum. Labioscrotal fusion was upset with separated folds resembling labia majoris and a structure that seemed to be vaginal introitus. The ultrasonographic study eliminated the possibility of uterus and ovaria and showed the presence of testis in the inguinal canal. Sexual chromatin in interphase cells of the oral mucosa indicated 0 Barr corps and the chromosomal study showed normal male cariotype (46, XY), so this case was considered as male pseudohermaphroditism. Sexual differentiation disorders were reviewed.

Diferenciación sexual en la langosta de agua dulce Cherax quadricarinatus (Decapoda: Parastacidae) / Sexual differentiation in the freshwater crayfish Cherax quadricarinatus (Decapoda: Parastacidae)

Determinamos el momento del desarrollo postembrionario en que se produce la diferenciación sexual primaria en la langosta Cherax quadricarinatus. Esta es evidenciada por la presencia de las gónadas y sus respectivos conductos. También determinamos la diferenciación sexual definida por la aparición de los caracteres sexualessecundarios. Se observaron 797 machos, 506 hembras y 456 individuos intersexos de 0.02 a 89.96 g (de criadero y laboratorio). Disecamos una submuestra de 106 machos, 69 hembras y 59 individuos intersexos para la caracterización macroscópica de la estructura gonadal. La diferenciación de los gonoporos se inicia aproximadamente a los 0.10 g, en sincronía con la diferenciación del sistema reproductor en machos, hembras e intersexos. La adquisición de la forma definitiva de ovario, oviducto, testículo y vaso deferente son posteriores. El appendix masculina iniciasu diferenciación a los 0.12-0.2 g y adquiere los rasgos característicos del appendix de los adultos a partir de 1-2 g.La diferenciación de la mancha roja (red patch) ocurre a partir de los 2.3 g.

We determined the earliest stage of postembryonic development at which primary and secondary sexual differentiations occur in the freshwater (“red claw”) crayfish Cherax quadricarinatus. For this purpose,797 males, 506 females and 456 intersex specimens within a weight range of 0.02-89.96 g were observed under stereoscopic microscope to determine the presence of the genital openings at the basis of the third (females) or fifth (males) pair of pereiopods. Animals presenting both pairs of genital openings were considered as intersex. A subsample of 106 males, 69 females and 59 intersex were dissected for the macroscopic characterization of gonad morphology. The development of the genital openings began approximately at 0.10 g, simultaneously with the differentiation of the reproductive system in females, males and intersex. Although the differentiation of the reproductive system started very early in the postembryonic development, the definitive form and colour of ovaries, oviducts, testes and vasa deferentia was acquired later. The differentiation of the appendix masculina began at 0.12-0.2 g and acquired the elongated shape of the adult at 1-2 g. The soft red patch characteristic of adult males started at 2.3 g of body weight in both chelipeds.

Morphological study of the spermatogenesis in the teleost Piaractus mesopotamicus

The spermatogenesis of Piaractus mesopotamicus was investigated under light and transmission electron microscopy. The specimens were captured from their natural environment (Rio Miranda and Rio Aquidauana, Pantanal Matogrossense, Brazil) during April and September. The results were compared with the spermatogenic data of specimens under captivity condition. In both conditions, P. mesopotamicus presented the typical spermatogenesis pattern of the teleost fishes, showing no significative differences. The spermatozoon was classified as type I, which has a globular head without acrosome, a short middle piece and a long tail constituted only by the flagellum. This type of spermatozoon is considered the basic type in fishes.

Sexo ambiguo: prevalencia al nacimiento en la maternidad del Hospital Clínico de la Universidad de Chile / Ambiguous sex: prevalence at birth in a university obstetric service in Santiago, Chile

Background: Ambiguous sex has a great phenotypic variability and is a serious medical and social problem. Aim: To study the prevalence of ambiguous sex among newborns. Material and methods: As part of the ECLAMC (Cooperative Latin American Study of Congenital Malformations) all newborns with malformations are registered and the next normal newborn is considered as a control. Results: 50.253 births occurred (between 1982 and 1999) in the University of Chile Maternity Hospital. The rate of congenital malformations was 6.78 percent and the prevalence of ambiguous sex was 4.7 per 10.000 births. Affected children had a lower birth weight, lower gestational age and a lower maternal age than controls. The most frequent associated malformations were of the urinary (64 percent) and cardiovascular systems (60.7 percent). Thirty two percent of affected children had specific syndromes. Conclusions: The prevalence of ambiguous sex in this study was 4.7 per 10.000 births, which is higher than that reported in the ECLAMC (1.9 per 10000)

Diferenciación sexual embrio-fetal: de las móleculas a la anatomía / Fetal sex differentiation: from molecules to anatomy

El sexo del embrión queda determinado en el momento de la fecundación según que el espermatozoide contenga un cromosoma X o un cromosoma Y. Sin embargo, trascurren varias semanas durante la embriogénesis humana sin que existan diferencias evidentes-aún al microscopio- entre un feto de sexo femenino y uno de sexo masculino. A partir de la expresión del gen SRY en los fetos XY, las futuras gónadas inician una serie de eventos caracterizados por expresión de proteínas, que determinan cambios citológicos, histológicos y funcionales característicos de los testículos. Este evento relativamente temprano en el desarrollo del sexo se denomina determinación sexual, dada su importancia determinante en el resto de los eventos que se suceden luego. Los testículos secretan dos hormonas, hormona ani-Mülleriana y testorona, cuya acción provoca la masculinización de los esbozos de los órganos genitales internos y externos, que no mostraban hasta entonces diferencias entre los sexos. El proceso de diferenciación de los genitales se denominan diferenciación sexual fetal. Poco se conoce hasta hoy sobre los mecanismo que inducen a las gónadas a tomar caminos ováricos en el feto XX. Es sabido desde hace tiempo, en cambio, que la falta de las hormonas testiculares resulta en la feminización de los genitales internos y externos, independientemente de la existencia o ausencia de ovarios. El conocimiento de los mecanismos moleculares, celulares y endocrinos involucrados en el desarrollo sexual fetal permiten comprender mejor la patología resultante de sus respectivas alteraciones que generan cuadros clínicos conocidos como ambigüedades sexuales

Hormônio anti-mülleriano: revisäo e contribuiçäo para a investigaçäo das ambigüidades genitais / Antimullerian hormone: review and contribution for the investigations of genital ambiguities

A investigaçäo etiológica das ambigüidades genitais com cariótipo 46,XY apresenta dificuldades freqüentes. A funçäo testicular tem sido tradicionalmente avaliada pela capacidade esteroidogênica das célulacs de Leydig e pela espermatogênese. Recentemente, demonstrou-se qua a avaliaçäo sérica do hormônio anti-mülleriano (HAM)como marcador da funçäo das célilas de Sertoli pode ser de grande valia nesta investigaçäo. O objetivo desta revisäo é apresentar aspectos históricos e fisiológicos do HAM, e sua utilidade na investigaçäo diagnóstica de pacientes com intersexo. Também é mostrada a experiência dos autores na avaliaçäo de intersexo com dosagens combinadas de andrógenos, HAM e testosterona.

Ambigüedad de genitales I. Abordaje inicial del paciente / Ambigous genitalia. Initial diagnosis approach

Se presentan los criterios para el abordaje diagnóstico inicial de pacientes con alteraciones en la diferenciación sexual, de acuerdo a los lineamientos del Grupo Para el Estudio del Intersexo del Instituto Nacional de Pediatría. Una vez definidas las alteraciones genitales de cada paciente, así como sus antecedentes personales y familiares, se sugiere un protocolo de exámenes paraclínicos indispensables para iniciar el abordaje sindromático. Se hace énfasis en la necesidad de no establecer una asignación sexual social ni funcional hasta no haber esclarecido la etiología precisa del trastorno.