Phthalates are chemicals interfering with the function of testosterone and are suspected to play a role in the emergence of neurodevelopmental diseases. This could be due to interference with brain development for which optimal testosterone levels are essential. We investigated the effect of prenatal and early postnatal exposure to a phthalate mixture on the anogenital distance (AGD), plasma testosterone levels and social behavior in rats. Pregnant rats were exposed to a mixture of diethylhexyl, diisononyl and dibutyl phthalate, each at a dose of 4.5 mg/kg/day, from gestational day 15 to postnatal day 4. A social interaction test was performed to assess sociability in the three ontogenetic stages (weaning, puberty, adulthood). AGD was measured in adulthood to assess changes in prenatal testosterone levels. Plasma testosterone levels were measured in adults by a radioimmunoassay. The total frequency and time of socio-cohesive interactions were decreased in phthalate exposed females in weaning, puberty and adulthood. Phthalate exposed males showed a decrease in the frequency of social interactions in weaning only. Shorter anogenital distance was observed in adult males exposed to phthalates. Decreased testosterone levels were observed in the exposed group in both sexes. Our results suggest that early developmental phthalate exposure may play an important role in the hormonal and behavioral changes associated with several neurodevelopmental diseases.

• MeSH
• dibutylftalát toxicita   MeSH
• diethylhexylftalát toxicita   MeSH
• krysa rodu rattus MeSH
• kyseliny ftalové toxicita   MeSH
• matka - expozice noxám škodlivé účinky   MeSH
• novorozená zvířata MeSH
• pohlavní dospělost MeSH
• pohlavní orgány účinky léků   patologie   MeSH
• potkani Wistar MeSH
• sociální chování * MeSH
• těhotenství MeSH
• testosteron krev   MeSH
• zpožděný efekt prenatální expozice chemicky indukované   patologie   MeSH
• zvířata MeSH
• zvláčňovadla toxicita   MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Phthalate esters are ubiquitous environmental pollutants widely used as plasticizers, which have been shown to interfere with both endocrine regulation and development of reproductive organs. In the present study, we examined the impact of diethylhexyl phthalate (DEHP) and dibutyl phthalate (DBP) on the proliferation of androgen-sensitive human prostate carcinoma LNCaP cells and related events. The results showed that both compounds were able to inhibit cell cycle progression in a dose-dependent manner. However, only DEHP was found to weakly reduce androgen receptor (AR) protein levels after long-term exposure, while only DBP partially inhibited expression of the prostate-specific antigen (KLK3) gene, a model AR transcriptional target. This indicated that inhibition of cell proliferation was likely independent of any AR modulations. Both phthalates induced suppression of cell proliferation, but none of them affected the levels of markers associated with neuroendocrine transdifferentiation (NED) in LNCaP cells. Taken together, the presented data indicate that phthalates may exert long-term negative effects on the proliferation of prostate epithelial cells derived from the carcinoma model, which are, nevertheless, largely independent of the modulation of AR expression/activity, and which do not alter further processes associated with NED.

• MeSH
• biologické modely * MeSH
• buněčný cyklus účinky léků   MeSH
• dibutylftalát toxicita   MeSH
• diethylhexylftalát toxicita   MeSH
• kyseliny ftalové toxicita   MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádory prostaty genetika   patologie   MeSH
• neuroendokrinní buňky účinky léků   patologie   MeSH
• počet buněk MeSH
• proliferace buněk účinky léků   MeSH
• prostatický specifický antigen genetika   metabolismus   MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• transdiferenciace buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH