In Utero Exposure to Di(n-butyl)phthalate Induces Morphological and Biochemical Changes in Rats Postpuberty

Abstract

Pregnant Sprague-Dawley rats were orally administered di( n-butyl)phthalate (DBP; 100 mg/kg/day) on gestation days (GD) 12 to 21. We investigated the male offspring and probed morphological alterations in Sertoli cells at 7, 9, 14, and 17 weeks of age. Parameters assessed in this study included offspring number, sex ratios, body weights, testis weights, seminiferous tubule (ST) profile numbers and diameters, number of vimentin-labeled Sertoli cells, and both testosterone and follicle-stimulating hormone (FSH) levels. Testicular weight/body weight ratios and the numbers and diameters of ST in maximum transverse testicular sections were statistically similar at weeks 7 and 9; however, at weeks 14 and 17, they were statistically different and displayed higher BrdU-positive Sertoli cells/Sertoli cell ratios in the DBP treatment group. Noteworthily, the serum FSH levels were higher and testicular testosterone levels were lower in the DBP treatment group. To our knowledge, the present study is the first to report that in utero DBP exposure significantly increased Sertoli cell numbers and their cellular proliferation from postpuberty to adulthood, with a significant decrease in testicular testosterone and an increase in FSH.

Perinatal exposures to phthalates and phthalate mixtures result in sex-specific effects on body weight, organ weights and intracisternal A-particle (IAP) DNA methylation in weanling mice

“…This study is the first to examine body weight effects following developmental DBP exposure in mice, but studies in rats have also demonstrated mixed effects on offspring body weight 37 53 , 54 …”

“…This study is the first to examine body weight effects following developmental DBP exposure in mice, but studies in rats have also demonstrated mixed effects on offspring body weight. 37,53,54 This is the first animal study to examine the impact of developmental exposures to mixtures of phthalates on body weight. Exposure to phthalate mixtures did not appear to result in an exaggerated effect on PND21 body weight; females exposed to DEHP + DINP did not weigh significantly more than controls, and those exposed to DEHP + DINP + DBP weighed more than controls to a moderate degree of statistical significance.…”

Assessing effects of germline exposure to environmental toxicants by high-throughput screening in C. elegans

“…Higher levels have been detected in human urine, follicular fluid, and serum in different occupationally exposed groups [21,24]. In vitro and animal studies have shown that DBP disrupts the reproductive system resulting in inhibition of ovarian antral follicle growth and viability, altered gene expression in ovaries, testicular malformation and dysfunction, inhibition of spermatogenesis, and altered androgen signaling in males [25–28]. In humans, a significant inverse relationship has been observed between levels of DBP metabolites (i.e.…”