A previous study has demonstrated exposure of Brazilian pregnant women to diisopentyl phthalate (DiPeP), which reduces fetal rat testosterone production in a dose-responsive manner. In this study, we examined gene expression of steroidogenic proteins in rat fetal testes and investigated the effects of in utero and lactational DiPeP exposure on male rat reproductive development and function. For the prenatal experiment, we orally exposed pregnant Wistar rats to DiPeP or di-n-butyl phthalate (reference phthalate) at 0, 125, 250, and 500 mg/kg/day from gestation day 14–18 and the fetal testis was evaluated for transcript expression of Star, Cyp11a1, Cyp17a1, Cyp19a1, Insl3, Ar, Esr1, Esr2, and Gper1 by real-time quantitative PCR (RT-qPCR). Diisopentyl phthalate lowered mRNA levels of key steroidogenic proteins, lending support to the previously reported reductions in fetal testosterone production. Diisopentyl phthalate also lowered fetal testis transcript levels of Insl3 and changed gene expression of some steroid hormones receptors. For the postnatal experiment, pregnant rats were exposed orally to vehicle (canola oil) and 4 DiPeP doses (1, 10, 100, and 300 mg/kg/day) between gestation day 10 and postnatal day 21. Diisopentyl phthalate induced a range of reproductive and antiandrogenic effects that are typical of the rat phthalate syndrome, including reduced anogenital distance at the highest dose, reduced weight of seminal vesicles at 10 mg/kg/day and above, and testicular morphological and functional changes. Signs of fetal toxicity were observed at the highest dose. Together, our results indicate that DiPeP, a compound relevant to the human exposure scenario, is one of the most active antiandrogenic phthalates.

Phthalates are found in different plastic materials, such as packaging, toys and medical devices. Some of these compounds are endocrine disruptors, comprising substances that are able to induce multiple hormonal disturbances and downstream developmental effects, including the disruption of androgen-dependent differentiation of the male reproductive tract and changes in pathways that regulate hormone-dependent behaviours. In a previous study, metabolites of diisopentyl phthalate (DiPeP), a potent anti-androgenic phthalate, were found in the urine of Brazilian pregnant women.Therefore, the present study aimed to evaluate the effects of DiPeP exposure during critical developmental periods on behaviours controlled by sex hormones in rats.Pregnant Wistar rats were treated with DiPeP (1, 10 or 100 mg kg day -1 ) or canola oil by oral gavage between gestational day 10 and post-natal day (PND) 21. Male offspring were tested in a behavioural battery, including the elevated plus maze task, play behaviour, partner preference and sexual behaviour. After the behavioural tests, the hypothalamus and pituitary of these animals were removed on PND 60-65 and PND 145-160 to quantify gene expression for aromatase, androgen receptor (Ar) and oestrogen receptors α (Esr1) and β (Esr2). Male rats exposed to 1 and 10 mg kg day -1 DiPeP displayed no preference for the female stimulus rat in the partner preference test and 1 mg kg day -1 DiPeP rats also showed a significant increase in mount and penetration latencies when mated with receptive females. A decrease in pituitary Esr1 expression was observed in all DiPeP treated groups regardless of age. A reduction in hypothalamic Esr1 expression in rats exposed to 10 mg kg day -1 DiPeP was also observed. No significant changes were found with respect to Ar, Esr2 and aromatase expression in the hypothalamus. These results suggest that DiPeP exposure during critical windows of development in rats may induce changes in behaviours related to mating and the sexual motivation of males. K E Y W O R D S anti-androgens, behaviour, diisoamyl phthalate, male offspring rats, phthalates S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Neubert da Silva G, Zauer Curi T, Lima Tolouei SE, et al. Effects of diisopentyl phthalate exposure during gestation and lactation on hormonedependent behaviours and hormone receptor expression in rats. J Neuroendocrinol. 2019;31:e12816. https ://doi.

Talinum paniculatum (Jacq.) Gaertn. (Talinaceae), popularly known as “major gomes,” is a Brazilian Cerrado plant used in traditional medicine and as a food source. Recent studies have demonstrated its diuretic effects. However, no studies have been performed on its effects on the reproductive system. Therefore, we aimed to investigate the effects of the ethanol-soluble fraction of T. paniculatum leaves (ESTP) on general toxicity and on the pubertal development of male and female Wistar rats. For this purpose, the uterotrophic and the pubertal assays were performed. In the uterotrophic test, female immature rats were treated for three consecutive days with 30, 100, or 300 mg/kg of ESTP. Uterus without luminal fluid was weighed and the relative weight calculated. For the pubertal assay, male and female immature rats were submitted to 30-day treatment with 30 or 300 mg/kg of ESTP. Clinical signs of toxicity, biochemical, and histopathological parameters were evaluated. ESTP treatment did not promote estrogenic effects in female rats. In the pubertal test, no daily signs of toxicity or weight loss were observed. Moreover, ESTP did not affect the onset of vaginal opening and preputial separation and did not cause significant changes in biochemical parameters as well as in organ weight and histopathological analyses of animals.

No abstract

No abstract