Dichlorodiphenyldichloroethylene Exposure during the First Trimester of Pregnancy Alters the Anal Position in Male Infants

Abstract

Anogenital distance (AGD) at birth is regarded as a useful measurement that reflects the prenatal androgenic status in rodents. However, the impact of xenoantiandrogens on human development is largely unknown. The aim of this study was to evaluate the potential antiandrogenic impact of prenatal DDT metabolites (p,p′-DDE and p,p′-DDT) exposure on infant AGD, using a non-age–dependent anal position index (API). As part of an ongoing perinatal cohort study on the effects of organochlorine pesticides in children’s neurodevelopment, we conducted a cross-sectional study in 71 infants (37 males and 34 females). Maternal serum levels of DDT metabolites (p,p′-DDE and p,p′-DDT) before and during each trimester of pregnancy were determined by electron capture gas–liquid chromatography. During postnatal home visits at 3, 6, and 12 or 18 months of age, the children’s weight and API were evaluated. Multiple lineal regression models were used to estimate the potential endocrine disruptor activity of prenatal p,p′-DDE exposure. Boys had significantly higher API values than girls (0.6 versus 0.5; P < 0.001). Only among boys, a doubling increase of maternal p,p′-DDE serum levels during the first trimester of pregnancy, were associated with a significant reduction of API (β = −0.02; P = 0.02). No effect of p,p′-DDT on AGD was observed. Evidence of the effect of prenatal p,p′-DDE on external genital differentiation is scarce and not consistent in the literature. Further studies are needed to confirm a hormonal disruptive effect on the development of external genitalia, due not only to p,p′-DDE but also due to other antiandrogenic persistent compounds.

The relationship between anogenital distance and age

“…(Larson, 1997) Human studies in infants have established that boys have longer perineal lengths than girls. (Salazar-Martinez et al, 2004;Torres-Sanchez et al, 2008;Thankamony et al, 2009;Sathyanarayana et al, 2010) Investigators have used the anogenital distance as a marker for normal genital development. Hsieh et al demonstrated shorter anogenital distances in boys with genital anomalies (i.e.…”

“…(Swan et al, 2005;Scott et al, 2007;Hsieh et al, 2008;Torres-Sanchez et al, 2008) As it is a sexually dimorphic measure, AGD was initially used to sex animals. (Marois, 1968;Greenham & Greenham, 1977;Hsieh et al, 2008) More recently, human studies have also shown that boys have longer perineal lengths than girls.…”

“…(Marois, 1968;Greenham & Greenham, 1977;Hsieh et al, 2008) More recently, human studies have also shown that boys have longer perineal lengths than girls. (SalazarMartinez et al, 2004;Torres-Sanchez et al, 2008;Thankamony et al, 2009;Sathyanarayana et al, 2010) Investigators have also used AGD to show that agents which disrupt androgen signalling in animal models can lead to abnormal genital lengths and even altered testicular function as measured by testosterone and sperm production. (Foster et al, 2001;Scott et al, 2008;MartinoAndrade et al, 2009;Cowin et al, 2010) Moreover, rodent studies suggest a narrow masculinization programming window, suggesting that prenatal influences on androgen signalling have more profound impacts on genital lengths than postnatal insults.…”

Anogenital distance as a measure of human male fertility

“…[1][2][3] Moreover, human studies in infants have also established that boys have longer perineal lengths than girls. [4][5][6][7] Investigators have used the anogenital distance as a marker for normal genital development. In humans, girls with CAH have been shown to have longer perineal lengths than their normal counterparts.…”

“…[1][2][3] More recently, human studies have also demonstrated that boys have longer perineal lengths (or AGD) than girls. [4][5][6][7] Human studies have also linked adult testicular function, as assessed by sperm and testosterone production, to AGD. [8][9][10] As AGD seems to be constant across a man's adult life, the clinical utility of AGD has been suggested in studies of infertile men.…”