Testicular toxicity in mice exposed to terephthalic acid in utero and during lactation

Terephthalic acid (TPA) is a worldwide aromatic compound widely used to manufacture resins and the raw material for the polymerization reaction with ethylene glycol to produce polyethylene terephthalate, known as PET. The use of TPA extends to the synthesis of phthalates, plasticizers used in various industrialized products such as toys and cosmetics. The present study aimed to evaluate the testicular toxicity of terephthalic acid on male mice exposed in utero and during lactation to TPA in different developmental windows. The animals were treated intragastric with TPA at stock dispersal dosages corresponding to 0.0014 g/ml and 0.56 g/ml of TPA in 0.5% v/v carboxymethylcellulose as well as the control dose, composed solely of dispersion of carboxymethylcellulose (0.5% v/v). Four experimental windows were established: group I—treatment in utero, in the fetal period (gestational day—GD 10.5–18.5), with euthanasia at GD 18.5; group II—treatment in utero, in the fetal period (GD 10.5–18.5) and the lactational period (postnatal day (PND-15)), with euthanasia at 15 days; group III—treatment in utero in the fetal period (DG 10.5–18.5) with euthanasia at 70 days (age of sexual maturity, PND 70); group IV—treatment in utero, in the fetal period (GD 10.5–18.5) and the lactational period (PND-15), with euthanasia at 70 days (PND70). The results indicate that TPA changes the reproductive parameters (testicular weight, GI, penis size, and anogenital index) only at the dose of 0.56 g/ml in the fetal period. Data on the volumetric ratio of the testis elements show that the dispersion with the highest concentration of TPA significantly altered the blood vessel/capillary, lymphatic vessel, and connective tissue percentages. Only at the dose of 0.56 g/ml TPA was it effective in decreasing the Leydig and Sertoli cell numbers of the euthanized animals at GD 18.5. In group II, TPA increased the diameter and lumen of seminiferous tubules, which indicates that TPA accelerated the maturation process of Sertoli cells without changing the number and the nuclear volume of these cells. The Sertoli and Leydig cell numbers of the 70-day animals exposed to TPA in the gestational and lactational period were similar to the control. Therefore, the present study is the first in the literature to show that TPA presents a testicular toxicity during fetal (DG18.5) and postnatal life (PND15), without repercussion in adulthood (70 days).