Exposure to the plasticizer DEHP during development and lactation alters the pituitary-testicular axis

Abstract

Phthalates are additives that give flexibility to polyvinyl chloride (PVC), being Di-2-ethylhexyl phthalate (DEHP) the most widely used due to its low cost and usefulness in the industry. It crosses the placental barrier and interferes with hormonal signaling, acting as an endocrine disruptor, affecting fetal development. The aim of this study was to analyze the effect of exposure to DEHP during pregnancy and lactation on the pituitary-gonadal axis.

Male Wistar rats exposed during gestation and lactation to DEHP (200 µg/kg/day) or vehicle (corn oil) were sacrificed at 21 days postnatal (DPN, prepubertal period) and 75 DPN (adulthood).  Stem blood was obtained for serum testosterone determination. The anterior pituitary glands were processed to determine the percentage of gonadotrophs (immunodetection of βLH) and for the analysis of the proliferative capacity of this endocrine population (Ki-67), by flow cytometry and immunofluorescence. The testis and corpus epididymis were processed for optical morphological and ultrastructural analysis. Statistical analysis ANOVA Tukey (P<0.05) was performed.

Exposure to DEHP significantly reduced serum testosterone concentration by approximately 50% and produced a shortening of the anogenital distance, both in prepuberty and in adulthood, which would be indicative of androgen deficiency during development. In addition, exposure to DEHP decreased the percentage of pituitary gonadotropic cells and inhibited the proliferation of this endocrine cell type. In the testicle, DEHP induced degenerative changes in the seminiferous tubules, with a decrease in the number of layers of the sperm progeny, evidence of hypospermatogenesis, as well as disorganization of the maturational stages. In the epididymis, a significant decrease in the height of the epithelium was observed without alteration of the tubular diameter.

These results suggest that during development, exposure to DEHP disturbs the fetal androgenic environment and alters the pituitary-testicular axis, decreasing the population of gonadotrophs in the pituitary gland and altering testicular function.