P-081 In utero exposure to diisopentyl phthalate (DiPeP) disrupts the expression of steroidogenesis-related genes and induces multinucleated gonocytes in the fetal rat testis

Abstract Study question Can the plasticizer diisopentyl phthalate (DiPeP) disrupt testosterone biosynthesis and alter fetal rat testis histology similarly to other common toxic phthalates? Summary answer DiPeP can dose-dependently suppress mRNA levels of steroidogenic genes induce multinucleated gonocytes in testis, resembling effects phthalates. What is known already an uncommon phthalate, whose metabolites have been ubiquitously detected urinary samples from Brazilian pregnant women children. These results, which contrast with undetected human biomonitoring studies worldwide, led us investigate reproductive developmental toxicity rats. Our preliminary data indicate that a potent antiandrogenic but no conducted assess impact exposures on incidence feature syndrome. design, size, duration Pregnant Wistar rats (n = 7-9 dams/group) were treated orally (gavage) 0 (control), 11, 33, 100 mg/kg/day between gestation days 14-20. Dose based prior canola oil was used as vehicle. On day 20, dams euthanized up three male fetuses each litter removed for collection testes assessment study endpoints. Participants/materials, setting, methods Fetal enzyme immunoassay quantification production following ex vivo incubation culture media, analysis insulin-like factor 3 (Insl3) by quantitative polymerase chain reaction (qPCR), histological optical microscopy. Main results role chance No signs systemic observed indicated lack alterations maternal body weights unchanged number, viability, weight fetuses. There significant changes at any dose. hand, induced reductions expression key genes, including suppressed acute regulatory protein (Star) cytochrome P450 family 11 subfamily A member 1 (Cyp11a1) 17 (Cyp17a1) 33 mg/kg/day. Gene Insl3, essential process descent, reduced highest dose 58% relation control, this change not (p 0.07). The number gonocytes, corrected testicular cord sections or total area analyzed cords significantly increased groups exposed Chance unlikely explanation our considering dose-dependent responses consistency findings data. Limitations, reasons caution tested doses are higher than expected exposure animal-to-human extrapolation should be done caution. Wider implications suppresses induces testis. endpoints seem more sensitive inhibition production. Although lower here, potentially act cumulatively chemicals share similar mechanisms. Trial registration applicable