Anogenital distance in human male and female newborns: a descriptive, cross-sectional study

Salazar-Martı́nez, Eduardo; Romano-Riquer, Patricia; Yanez-Marquez, Edith; Longnecker, Matthew P.; Hernández-Ávila, Mauricio

doi:10.1186/1476-069x-3-8

Cited by 199 publications

(222 citation statements)

References 35 publications

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“…A measurement of AGD is considered to be a bioassay for fetal androgen action [20]. Alterations in AGD in early postnatal life were not only observed in male rats exposed to the different doses (100 mg/kg BW/day) of DEHP, but also in all the Flu-treated groups.…”

Section: Discussionmentioning

confidence: 94%

Differential Effects of Flutamide and Di-(2-ethylhexyl) phthalate on Male Reproductive Organs in a Rat Model

Jung

Dang

et al. 2009

Journal of Reproduction and Development

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Abstract. Endocrine disruptors (EDs) with androgenic and anti-androgenic effects may alter reproductive function by binding to androgenic receptors (AR) and inducing or modulating AR-dependent responses in the male reproductive system. However, the molecular mechanism(s) underlying these events remains unclear. In the present study, pregnant Sprague Dawley (SD) rats were treated with testosterone propionate (TP), flutamide (Flu) and di-(2-ethylhexyl) phthalate (DEHP) from gestation days (GD) 11 to 21. Interestingly, maternal exposure to Flu or DEHP caused fluctuations in the neonatal levels of serum testosterone (T) and luteinizing hormone (LH). Serum testosterone and LH were upregulated by Flu, but these hormones were down-regulated by DEHP. The anogenital distances (AGD) of male newborns were determined at post-neonatal days (PND) 1, 21 and 63. Male rats treated prenatally with DEHP (100 mg/kg mother's body weight) or Flu showed an AGD shorter than that of control rats. At PND 63, sperm concentration, viability and motility were reduced in the maternal DEHP and Flu-treated groups. The numbers of seminiferous tubules were reduced in the Flu and DEHP-treated offspring when compared with the vehicle-and TPtreated groups, and the tubules of the testes at PND 63 were disrupted by a high dose of Flu. In addition, we found differential gene expression patterns by microarray analysis following ED exposure, particularly in sex determinationrelated genes. Although Flu and DEHP are considered to be identical with regard to their anti-androgenic effects, their effects on developing male reproductive organs were distinct, suggesting that Flu competes with endogenous T, while DEHP influences a different step in androgenesis. Key words: Flutamide, Male reproduction, Phthalate (J. Reprod. Dev. 55: [400][401][402][403][404][405][406][407][408][409][410][411] 2009) ecently, environmental, anti-androgenic compounds have been recognized as endocrine disruptors (EDs) because of their hormone-like activities. Anti-androgenic chemicals have the potential to interfere with male reproductive development and function in humans and animals. The EDs are thought to act via many mechanisms, such as by decreasing androgen synthesis, exerting effects on the pituitary-gonadal axis and/or blocking the androgen receptor (AR) [1,2]. The consequences of these actions may cause abnormal hormonal regulation and gene expression.It has been demonstrated that the AR plays a critical role in control of male sexual differentiation. During mammalian sex differentiation, the androgens, testosterone (T) and its metabolite dihydrotestosterone (DHT), produced by the fetal/neonatal male during sexual differentiation are critical factors in the male phenotype [3]. Sex development continues postnatally with the onset of secondary sexual characteristics at puberty and the acquisition of reproductive capacity. In addition, the differentiation of the Wolffian structures (e.g., the epididymis, vas deferens and seminal vesicles) appears to be T-mediated, while ma...

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Section: Discussionmentioning

confidence: 94%

Differential Effects of Flutamide and Di-(2-ethylhexyl) phthalate on Male Reproductive Organs in a Rat Model

Jung

Dang

et al. 2009

Journal of Reproduction and Development

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“…LW flutamide treatment had no effect on phallus length (P > 0.05; Figure 1G). Masculinization of anogenital distance (AGD), which is approximately twice as long in males as females in humans (39) and rats (36), was also completely prevented by EW, but not LW, flutamide treatment ( Figure 1F); exposure to MW flutamide treatment significantly reduced AGD, compared with control males (P > 0.001; Figure 1F), but this reduction was far less dramatic than that induced by EW treatment. The flutamide-induced reduction in AGD was permanent, as it persisted until adulthood (data not shown).…”

Section: Figurementioning

confidence: 95%

Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism

Welsh¹,

Saunders²,

Fisken³

et al. 2008

J. Clin. Invest.

640

628

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Becoming a phenotypic male is ultimately determined by androgen-induced masculinization. Disorders of fetal masculinization, resulting in hypospadias or cryptorchidism, are common, but their cause remains unclear. Together with the adult-onset disorders low sperm count and testicular cancer, they can constitute a testicular dysgenesis syndrome (TDS). Although masculinization is well studied, no unifying concept explains normal male reproductive development and its abnormalities, including TDS. We exposed rat fetuses to either anti-androgens or androgens and showed that masculinization of all reproductive tract tissues was programmed by androgen action during a common fetal programming window. This preceded morphological differentiation, when androgen action was, surprisingly, unnecessary. Only within the programming window did blocking androgen action induce hypospadias and cryptorchidism and altered penile length in male rats, all of which correlated with anogenital distance (AGD). Androgen-driven masculinization of females was also confined to the same programming window. This work has identified in rats a common programming window in which androgen action is essential for normal reproductive tract masculinization and has highlighted that measuring AGD in neonatal humans could provide a noninvasive method to predict neonatal and adult reproductive disorders. Based on the timings in rats, we believe the programming window in humans is likely to be 8-14 weeks of gestation.

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“…Romano-Riquer et al (11) have developed an anthropometric protocol for the measurement of AGD in human males. Similarly, SalazarMartinez et al (12), have developed an anthropometric protocol for both male and female newborns. They measured the distance from the centre of the anus to the junction of the smooth perineal skin with the rugated skin of the scrotum in male new-borns and the centre of the anus to the posterior convergence of the fourchette in female infants.…”

Section: Measuringmentioning

confidence: 99%

Ano-genital distance in healthy Nigerian full-term newborn infants

Onyiriuka¹,

Elusiyan

2016

Sri Lanka J. Diabetes Endocrinol. Metab.

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Anogenital distance in human male and female newborns: a descriptive, cross-sectional study

Cited by 199 publications

References 35 publications

Differential Effects of Flutamide and Di-(2-ethylhexyl) phthalate on Male Reproductive Organs in a Rat Model

Differential Effects of Flutamide and Di-(2-ethylhexyl) phthalate on Male Reproductive Organs in a Rat Model

Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism

Ano-genital distance in healthy Nigerian full-term newborn infants

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