Prenatal exposure to phthalates is associated with decreased anogenital distance and penile size in male newborns

Abstract

Reproductive effects from phthalate exposure have been documented mostly in animal studies. This study explored the association between prenatal exposure to phthalate metabolites, anogenital distance and penile measurements in male newborns in Toluca, State of Mexico. A total of 174 pregnant women provided urine samples for phthalate analysis during their last prenatal visit, and the 73 who gave birth to male infants were included in the study. The 73 male newborns were weighed and measured using standardized methods after delivery. After adjusting for creatinine and supine length at birth, significant inverse associations were observed between an index of prenatal exposure to total phthalate exposure and the distance from the anus to anterior base of the penis (β = −0.191 mm per 1 µg/l, P = 0.037), penile width (β = −0.0414, P = 0.050) and stretched length (β = −0.2137, P = 0.034); prenatal exposure to mono-2-ethylhexyl phthalate exposure was associated with a reduction in the stretched length of the penis (β = −0.2604, P = 0.050). Human exposure to phthalates is a public health concern, and the system most vulnerable to its potential effects seems to be the immature male reproductive tract.

Man is not a big rat: concerns with traditional human risk assessment of phthalates based on their anti-androgenic effects observed in the rat foetus

“…Bustamante-Montes et al [42] confirmed these results [42]. They observed an inverse correlation between MEHP concentration in maternal urinary samples during the last trimester of pregnancy and AGD but not ASD, measured 24-48 h after birth, in 73 mother-son pairs in Mexico State.…”

Stress and Androgen Activity During Fetal Development

“…Further follow-up with the cohort indicated that girls exposed to more SLEs in utero also exhibited more masculine play behavior in early childhood than girls exposed to fewer SLEs (84). Numerous epidemiological studies have shown that as in animal models, prenatal exposure to the phthalate DEHP is associated with shorter AGD in infant boys (85)(86)(87)(88). Given that prenatal stress and prenatal phthalate exposure may both influence human AGD, we used Study for Future Families data to examine whether prenatal SLE exposure modifies associations between maternal DEHP metabolite concentrations and infant AGD.…”

Phthalate metabolism and kinetics in an in vitro model of testis development

“…Some phthalate diesters are known male reproductive toxicants and exposure at low levels is widespread in many human populations (Duty et al 2003; Bustamante-Montes et al 2013). Effects of phthalates on male reproductive endpoints in rats have been extensively studied and include hypospadias, cryptorchidism, decreased anogenital distance, and decreased testosterone levels in the testes (Mylchreest et al 1998; Gray et al 2000; Clewell et al 2010).…”

“…The origins of TDS are postulated to be due in part to early life-stage exposures to endocrine disrupting compounds such as phthalates (Skakkebaek et al 2001). Due to rising rates of effects described by TDS in some human populations, the possibility that phthalate exposures are contributing to human male reproductive disorders remains a concern (Martino-Andrade and Chahoud 2010; Bustamante-Montes et al 2013). In order to characterize the inherent capacity for the cells in the 3D-TCS to metabolize this important class of male reproductive toxicants, we exposed cells to two known reproductively toxic phthalates, dibutyl phthalate and diethylhexyl phthalate (DBP and DEHP, 100µM) as well as one non-reproductively toxic phthalate, diethyl phthalate (DEP, 150µM).…”