Effects of pubertal exposure to low doses of di-(2-ethylexyl)phthalate on reproductive behaviors in male mice.

Reproductive behaviors are tightly regulated by sex steroid hormones. Interference with these hormones or their neural signaling pathways leads to behavioral alterations. We have previously shown that oral exposure of adult male mice to di(2-ethylhexyl) phthalate (DEHP), an organic environmental endocrine disruptor, altered sexual behavior. In this study, we examined the effects of pubertal exposure to DEHP and analyzed whether pubertal and adult exposures to DEHP trigger long-term effects. For pubertal exposure, male mice were exposed orally to the vehicle or DEHP at 5 or 50 μg/kg/d from postnatal day (PND) 30 to PND60. Exposure was arrested and animals were analyzed on PND120. They exhibited normal olfactory preference but showed modified emission of ultrasonic vocalizations. DEHP exposure also affected partner preference and mating components. These modifications were associated with normal circulating testosterone levels and weight of androgen-sensitive tissues. In contrast, androgen receptor (AR) protein amount was reduced in the hypothalamic preoptic area in particular for the DEHP-50 group. Pubertal exposure also increased the anxiety-state level without changing circadian activity. When adult male mice were exposed to DEHP at the same doses from PND60 to PND105 and analyzed two months later, no effects of treatment on reproductive and anxiety-related behaviors or hypothalamic AR protein amount were seen. Our data show that pubertal exposure of male mice to DEHP induces long-term behavioral changes in contrast to the adult exposure. This highlights the sensitivity of the nervous system to low doses of DEHP during the critical period of puberty.