RESUMO
BACKGROUND: Measurement of rat anogenital distance (AGD) dates to at least 1912. Increased interest in endocrine disrupting chemicals and the use of AGD as a biomarker for fetal androgen effects have increased the number of studies with this endpoint in recent decades. A literature review revealed different landmarks, methods of measurement, and methods to adjust for body weight differences. AGD is often reported to hundredths of millimeters and as such, deserves precision in all these aspects. This paper presents recommendations for the measurement and analysis of rodent AGD. METHODS: Literature and regulatory guidance documents that mentioned or measured rodent AGD were reviewed. Four adjustment methods were evaluated using available online data from three rat studies each with two generations of offspring. RESULTS: Tabulation of studies reveals that species/stocks and time of data collection, but more importantly anatomical landmarks and methods of measurement have produced a variety of results which are difficult to compare. Not all studies have adjusted for test article effects on body weight (and thus size). The four adjustment methods were fairly comparable. CONCLUSION: Recommendations are as follows. A microscopic method should be used to measure AGD of late rodent fetuses and early postnatal pups. The caudal edge of the genital tubercle and the cranial edge of the anus are clear and identifiable landmarks. The simplest adjustment is to divide individual AGDs by the cube root of animals' body weight. These recommendations will help ensure data consistency and accuracy, and facilitate meaningful comparisons across laboratories and chemical classes.
Assuntos
Canal Anal , Animais , Ratos , Canal Anal/anatomia & histologia , Canal Anal/embriologia , Feminino , Masculino , Gravidez , Roedores/anatomia & histologia , Peso Corporal , Feto/anatomia & histologia , Genitália/anatomia & histologia , Genitália/embriologiaRESUMO
Objetivo: Verificar a incidência de acerto na identificação ultra-sonográfica precoce do sexo fetal. Método: Foram estudados prospectivamente 1.931 fetos, por meio de exames ultra-sonográficos transvaginais e complementados por exames transabdominais, em gestações entre nove e 12 semanas, na Clínica Obstétrica da Faculdade de Medicina da Universidade Federal do Rio de Janeiro (UFRJ) e na Clínica de Ultra-Sonografia Fórum. O falo (tubérculo genital) foi determinado como horizontal no sexo feminino e vertical no sexo masculino, através da imagem em plano sagital ao corpo fetal, e correlacionado ao sexo quando do exame morfológico realizado aós a 18ª semana de gestação. Resultados: O sexo fetal determinado pela avaliação ultra-sonográfica precoce coincidiu com o sexo avaliado em 81,7 por cento dos casos em gestações com nove semanas, em 95,5 por cento nas gestações com 10 semanas, em 92,9 por cento naquelas com 11 semanas e em 99,8 por cento nas gestações com 12 semanas. O sucesso da identificação aumenta com o progredir da gestação, obtendo-se a média global de 94,2 por cento de acerto no período estudado. O acerto no diagnóstico do sexo fetal aumenta com a experiência do operador. Conclusão: A determinação ultra-sonográfica do posicionamento do falo genital pode predizer o sexo fetal precocemente.
Purpose: To establish the percentage of correct early diagnosis of fetal gender. Methods: A prospective study was developed in a University Federal of Rio de Janeiro, Departament of Obstetrics an Gynecology and Clinic of Ultrasonographic Forum. 1,931 women underwent transvaginal and transabdominal sonography at 9-12 weeks gestation. Fetal gender was identified according to genital falo position (vertical-men or horizontal-female) at sagittal plane and confirmed after 18 weeks pregnancy, morphologic, karyotyping analysis or after birth. Results: The overall accuracy of correctly assigning fetal gender was 94,2 per cent. The sucess of identification increased with gestational age, being 81,7 per cent, 95,5 per cent, 92,9 per cent and 99,8 per cent at nine, 10, 11 and 12 weeks, respectively. The accuracy of correctly identifying fetal sex significantly changed with operator training. Conclusion: Early ultrasound can accurately determine fetal gender.
Assuntos
Feminino , Gravidez , Gônadas/embriologia , Gônadas , Análise para Determinação do Sexo , Ultrassonografia Pré-Natal/métodos , Ultrassonografia Pré-Natal/tendências , Ultrassonografia Pré-Natal , Desenvolvimento Fetal/fisiologia , Feto/embriologia , Genitália/embriologiaRESUMO
Different perturbations during fetal and post natal development unleash endocrine adaptations that permanently alter metabolism, increasing the susceptibility to develop later disease, process known as "developmental programming"'. Endocrine disruptor compounds (EDC) are widely spread on the environment and display estrogenic, anti-estrogenic or anti-androgenic activity; they are lypophilyc and stored for long periods on the adipose tissue. Maternal exposure to EDC during pregnancy and lactation produces the exposure of the fetus and neonate through placenta and breast milk. Epidemiological and experimental studies have demonstrated reproductive alterations as a consequence of intrauterine and/or neonatal exposure to EDC. Diethystilbestrol (DES) is the best documented compound, this synthetic estrogen was administered to pregnant women at the BO and 60 to prevent miscarriage. It was implicated in urogenital abnormalities in children exposed in utero and withdrawn from the market. The "DES daughters" are women with high incidence of vaginal hypoplasia, spontaneous abortion, premature delivery, uterine malformation, menstrual abnormalities and low fertility. The "DES sons" show testicular dysgenesis syndrome, which is characterized by hypospadias, cryptorchidism and low semen quality. This entity is also associated to the fetal exposure to anti-androgens as flutamide. The effects on the reproductive axis depend on the stage of development and the window of exposure, as well as the dose and the compound. The wide distribution of EDC into the environment affects both human health and ecosystems in general, the study of their mechanisms of action is extremely important currently.
Diversas perturbaciones durante el desarrollo fetal y posnatal desencadenan adaptaciones endocrinas que modifican permanentemente el metabolismo, incrementando la susceptibilidad para el desarrollo de enfermedades, proceso conocido como "programación durante el desarrollo". Los compuestos disruptores endocrinos (CDE) se encuentran en el medio ambiente y presentan actividad estrogénica, antiestrogénica o antiandrogénica; son altamente lipofílicos y se almacenan por periodos prolongados en el tejido adiposo. La exposición materna a CDE durante el embarazo y la lactancia permite su paso al producto a través de la placenta y la leche materna. Estudios epidemiológicos y experimentales han demostrado alteraciones en el eje reproductivo como consecuencia de la exposición intrauterina y/o neonatal a CDE. El compuesto mejor documentado es el dietilestilbestrol (DES), este estrógeno sintético fue administrado a mujeres embarazadas durante los 50s y 60s y retirado del mercado por su implicación en anormalidades urogenitales de los bebés expuestos in útero. Las denominadas "hijas del DES" son mujeres con alta incidencia de hipoplasia vaginal, malformaciones uterinas, irregularidades menstruales, baja fertilidad y alta prevalencia de aborto espontáneo y parto prematuro. Por su parte, "los hijos del DES" presentan una entidad clínica conocida como síndrome de disgenesia testicular caracterizado por hipospadias, criptorquidia y baja calidad del semen. Este síndrome también se asocia a la exposición fetal a compuestos antiandrogénicos como la ñutamida. Los efectos en el eje reproductivo dependen del estadio de desarrollo y del tiempo de exposición, así como de la dosis y el compuesto del que se trate. La extensa presencia de CDE en el ambiente afecta la salud humana e impacta al ecosistema en general por lo cual es de suma importancia el estudio de los mecanismos involucrados en su acción.