RESUMEN
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.
Asunto(s)
Canal Anal , Animales , Ratas , Canal Anal/anatomía & histología , Canal Anal/embriología , Femenino , Masculino , Embarazo , Roedores/anatomía & histología , Peso Corporal , Feto/anatomía & histología , Genitales/anatomía & histología , Genitales/embriologíaRESUMEN
Background: Evidence from animal studies has indicated that neonatal thyroid function is vital for the reproductive development. Anogenital distance (AGD), a sensitive biomarker of the fetal hormonal milieu, can be used to predict adult reproductive disorders. However, few human studies have examined the association between neonatal thyroid function and AGD. We aimed to explore their associations in a birth cohort study. Methods: Concentrations of thyroid stimulating hormone (TSH) and thyroid hormones (THs), including total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), and free thyroxine (FT4) were measured in cord plasma in the Shanghai-Minhang Birth Cohort. The offspring AGD (AGDAP [anus-penis] and AGDAS [anus-scrotum] for boys and AGDAC [anus-clitoris] and AGDAF [anus-fourchette] for girls), body weight and anogenital index (AGI = AGD/weight [mm/kg]) were obtained at each follow-up visit. In total, 344 children (194 boys and 150 girls) with cord plasma concentrations of THs and TSH and at least one AGD measurement at birth and at 6, 12, and 48 months of age were included. Multiple linear regression and generalized estimating equation (GEE) models were used to examine the associations of cord plasma concentrations of THs and TSH with AGI. Results: Multiple linear regression models showed inverse associations of TT4, FT3, and FT4 with female AGI, although statistical significance was only reached at birth, 6 and 48 months of age. These associations were also found in GEE models: higher TT4 and FT4 concentrations were associated with lower AGIAC (TT4: ß = -0.27, 95% CI: -0.50, -0.03 for middle vs. lowest tertile; FT4: ß = -0.38, 95% CI: -0.61, -0.16 for middle and ß = -0.30, 95% CI: -0.55, -0.04 for highest vs. lowest tertile). Besides, girls with the highest tertile of FT3 concentrations had lower AGIAF than those with the lowest tertile (the highest vs. lowest tertile: ß = -0.22, 95% CI: -0.36, -0.08). Positive associations between TSH and AGI at birth and at 12 months of age were observed in boys. Conclusions: This study provides further evidence on the effects of neonatal thyroid function on reproductive development at an early life stage.
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Canal Anal/anatomía & histología , Genitales/anatomía & histología , Glándula Tiroides/fisiología , Tirotropina/sangre , Tiroxina/sangre , Triyodotironina/sangre , Antropometría , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Pruebas de Función de la TiroidesRESUMEN
BACKGROUND: Prenatal exposure to endocrine-disrupting chemicals may impair genital development and alter reproductive tract anatomy. Anogenital distance (AGD) is a useful biomarker of exposure to chemicals that act as endocrine disruptors. We evaluated associations between prenatal and perinatal exposure to several persistent organic pollutants (POPs) and AGD in 4-year-old children. METHODS: Data were drawn from the INMA-Asturias cohort. Pediatricians measured the anofourchetal distance in female children and anoscrotal distance in male children. The anogenital index (AGI) was defined as the AGD divided by the child's weight at age of examination. We measured the levels of two hexachlorocyclohexane isomers, hexachlorobenzene, dichlorodiphenyltrichloroethane (DDT) and its metabolites, six polychlorinated biphenyl (PCB) congeners, and six polybrominated diphenyl ether (PBDE) congeners in maternal serum at 12 gestational weeks (n = 155) and in cord blood serum (n = 229). Anthropometric and parental sociodemographic variables were collected via face-to-face interviews. Linear regression models were used to evaluate the relationship between exposure to POPs and AGI, adjusted for confounders and stratified by sex. RESULTS: In male children, we found inverse associations between AGI and maternal concentrations of PCB-138 (ß = -0.041, 95% confidence interval [CI]: -0.074, -0.008, second tertile), PCB-153 (ß = -0.052, 95% CI: -0.085, -0.020, second tertile), PCB-180 ß = -0.065, 95% CI: -0.096, -0.035, second tertile; ß = -0.042, 95% CI: -0.073, -0.011, third tertile), PBDE-209 (ß = -0.031, 95% CI: -0.058, -0.006), cord serum concentrations of PCB-153 (ß = -0.029, 95% CI: -0.059, -0.000, second tertile; ß = -0.047, 95% CI: -0.085, -0.008, third tertile), and PCB-180 (ß = -0.041, 95% CI: -0.078, -0.005, third tertile). In female children, AGI was positively associated with maternal serum concentrations of PCB-101 (ß = 0.039, 95% CI: 0.002, 0.076, second tertile), and higher cord serum levels of 4,4'-DDT (ß = 0.032, 95% CI: 0.003, 0.061, third tertile) and 4,4'-DDE (ß = 0.040, 95% CI: 0.011, 0.069, third tertile). CONCLUSIONS: Our findings provide evidence of associations between specific POPs and AGI in boys and girls aged 4 years, and suggest that pre/perinatal exposure to POPs has a feminizing effect in males and a masculinizing effect in females.
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Canal Anal/anatomía & histología , Disruptores Endocrinos/sangre , Contaminantes Ambientales/sangre , Genitales/anatomía & histología , Éteres Difenilos Halogenados/sangre , Hidrocarburos Clorados/sangre , Efectos Tardíos de la Exposición Prenatal , Adulto , Antropometría , Monitoreo Biológico , Preescolar , Estudios de Cohortes , Femenino , Sangre Fetal/química , Humanos , Recién Nacido , Masculino , Exposición Materna , Intercambio Materno-Fetal , Embarazo , EspañaRESUMEN
PURPOSE: The purpose of this study was to find an objective criteria to determine the position of normal anus in Korean children and to evaluate the clinical significance of anterior displacement of anus in children with constipation. METHODS: Three hundred and thirty-nine normal children and 24 children with idiopathic constipation represented the basis of this study. The position of the normal anus was defined by the anogenital index, which is the distance from the anus to the vagina or scrotum divided by the distance between the vagina or scrotum and coccyx. RESULTS: The mean anogenital index were 0.54 +/- 0.08 in normal male children, and 0.52 +/- 0.04 in male with constipation (P>0.05). The mean anogenital index were 0.43 +/- 0.08 in normal female children, and 0.42 +/- 0.07 in female with constipation (P>0.05). The anogenital index was very constant by age except for late male childhood. The anogenital index in female was significantly lower than in the male (P0.05). CONCLUSION: The anogenital index is an objective criteria to define the position of normal anus or anterior displacement of anus. There is no correlation between anterior displacement of the anus and idiopathic constipation.