PMID- 20307648 OWN - NLM STAT- MEDLINE DCOM- 20100921 LR - 20161125 IS - 1873-1708 (Electronic) IS - 0890-6238 (Linking) VI - 29 IP - 4 DP - 2010 Jul TI - In utero exposure to di-(2-ethylhexyl) phthalate affects liver morphology and metabolism in post-natal CD-1 mice. PG - 427-32 LID - 10.1016/j.reprotox.2010.03.002 [doi] AB - The plasticizer di-(2-ethylhexyl)phthalate (DEHP) affects reproductive development, glycogen and lipid metabolism. Whereas liver is a main DEHP target in adult rodents, the potential impact on metabolic programming is unknown. Effects of in utero DEHP exposure on liver development were investigated upon treatment of pregnant CD-1 mice on gestational days (GD)11-19. F1 mice were examined at post-natal days 21 (weaning) and 35 (start of puberty): parameters included liver histopathological, immunocytochemical and alpha-fetoprotein (AFP) gene expression analyses. In utero DEHP exposure altered post-natal liver development in weanling mice causing significant, dose-related (i) increased hepatosteatosis, (ii) decreased glycogen storage, (iii) increased beta-catenin intracytoplasmic localization (females only). At puberty, significantly decreased glycogen storage was still present in males. A treatment-induced phenotype was identified with lack of glycogen accumulation and intracytoplasmic localization of beta-catenin which was associated with increased AFP gene expression. Our findings suggested that DEHP alters post-natal liver development delaying the programming of glycogen metabolism. FAU - Maranghi, Francesca AU - Maranghi F AD - Department of Food Safety and Veterinary Public Health, Veterinary and Food Toxicology Unit Istituto Superiore di Sanita, Rome, Italy. francesca.maranghi@iss.it FAU - Lorenzetti, Stefano AU - Lorenzetti S FAU - Tassinari, Roberta AU - Tassinari R FAU - Moracci, Gabriele AU - Moracci G FAU - Tassinari, Valentina AU - Tassinari V FAU - Marcoccia, Daniele AU - Marcoccia D FAU - Di Virgilio, Antonio AU - Di Virgilio A FAU - Eusepi, Agostino AU - Eusepi A FAU - Romeo, Antonella AU - Romeo A FAU - Magrelli, Armando AU - Magrelli A FAU - Salvatore, Marco AU - Salvatore M FAU - Tosto, Fabrizio AU - Tosto F FAU - Viganotti, Mara AU - Viganotti M FAU - Antoccia, Antonio AU - Antoccia A FAU - Di Masi, Alessandra AU - Di Masi A FAU - Azzalin, Gianluca AU - Azzalin G FAU - Tanzarella, Caterina AU - Tanzarella C FAU - Macino, Giuseppe AU - Macino G FAU - Taruscio, Domenica AU - Taruscio D FAU - Mantovani, Alberto AU - Mantovani A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100320 PL - United States TA - Reprod Toxicol JT - Reproductive toxicology (Elmsford, N.Y.) JID - 8803591 RN - 0 (CTNNB1 protein, mouse) RN - 0 (Environmental Pollutants) RN - 0 (Liver Glycogen) RN - 0 (RNA, Messenger) RN - 0 (alpha-Fetoproteins) RN - 0 (beta Catenin) RN - C42K0PH13C (Diethylhexyl Phthalate) SB - IM MH - Animals MH - Chemical and Drug Induced Liver Injury/*etiology/metabolism/pathology MH - Cytoplasm/metabolism MH - Diethylhexyl Phthalate/*toxicity MH - Environmental Pollutants/*toxicity MH - Fatty Liver/*chemically induced/metabolism/pathology MH - Female MH - Gene Expression/drug effects MH - Liver/*drug effects/growth & development/metabolism MH - Liver Glycogen/metabolism MH - Maternal Exposure MH - Mice MH - Mice, Inbred Strains MH - Pregnancy MH - Prenatal Exposure Delayed Effects/*chemically induced/metabolism MH - RNA, Messenger/metabolism MH - alpha-Fetoproteins/genetics/metabolism MH - beta Catenin/metabolism EDAT- 2010/03/24 06:00 MHDA- 2010/09/23 06:00 CRDT- 2010/03/24 06:00 PHST- 2009/12/22 00:00 [received] PHST- 2010/02/19 00:00 [revised] PHST- 2010/03/13 00:00 [accepted] PHST- 2010/03/24 06:00 [entrez] PHST- 2010/03/24 06:00 [pubmed] PHST- 2010/09/23 06:00 [medline] AID - S0890-6238(10)00044-4 [pii] AID - 10.1016/j.reprotox.2010.03.002 [doi] PST - ppublish SO - Reprod Toxicol. 2010 Jul;29(4):427-32. doi: 10.1016/j.reprotox.2010.03.002. Epub 2010 Mar 20.