PMID- 25445723 OWN - NLM STAT- MEDLINE DCOM- 20150429 LR - 20150112 IS - 1879-3169 (Electronic) IS - 0378-4274 (Linking) VI - 232 IP - 2 DP - 2015 Jan 22 TI - Inutero exposure to diisononyl phthalate caused testicular dysgenesis of rat fetal testis. PG - 466-74 LID - S0378-4274(14)01476-3 [pii] LID - 10.1016/j.toxlet.2014.11.024 [doi] AB - Diisononyl phthalate (DINP) is a synthetic material that has been widely used as a substitute for other plasticizers prohibited due to reproductive toxicity in consumer products. Some phthalates have been associated with testicular dysgenesis syndrome in male fetus when female pregnant dams were exposed to them. The present study investigated effects of DINP on fetal Leydig cell function and testis development. Female pregnant Sprague Dawley rats received control vehicle (corn oil) or DINP (10, 100, 500, and 1000 mg/kg) by oral gavage from gestational day (GD) 12 to 21. At GD 21.5, testicular testosterone production, fetal Leydig cell numbers and distribution, testicular gene and protein expression levels were examined. DINP showed dose-dependent increase of fetal Leydig cell aggregation with the low observed adverse-effect level (LOAEL) of 10 mg/kg and multinucleated gonocyte with LOAEL of 100 mg/kg. At 10 mg/kg, DINP also significantly increased fetal Leydig cell size, but inhibited insulin-like 3 and 3beta-hydroxysteroid dehydrogenase gene expression and protein levels. DINP inhibited testicular testosterone levels at 1000 mg/kg. The results indicate that in utero exposure to DINP affects the expression levels of some fetal Leydig cell steroidogenic genes, gonocyte multinucleation and Leydig cell aggregation. CI - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved. FAU - Li, Linxi AU - Li L AD - Center of Scientific Research, The 2nd Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. FAU - Bu, Tiao AU - Bu T AD - Center of Scientific Research, The 2nd Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. FAU - Su, Huina AU - Su H AD - Department of Anesthesiology, The 2nd Affiliated Hospital & Research Academy of Reproductive Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. FAU - Chen, Zhichuan AU - Chen Z AD - Department of Anesthesiology, The 2nd Affiliated Hospital & Research Academy of Reproductive Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. FAU - Liang, Yuyuan AU - Liang Y AD - Department of Anesthesiology, The 2nd Affiliated Hospital & Research Academy of Reproductive Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. FAU - Zhang, Gaolong AU - Zhang G AD - Department of Anesthesiology, The 2nd Affiliated Hospital & Research Academy of Reproductive Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. FAU - Zhu, Danyan AU - Zhu D AD - Department of Anesthesiology, The 2nd Affiliated Hospital & Research Academy of Reproductive Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. FAU - Shan, Yuanyuan AU - Shan Y AD - Department of Anesthesiology, The 2nd Affiliated Hospital & Research Academy of Reproductive Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. FAU - Xu, Renai AU - Xu R AD - Department of Anesthesiology, The 2nd Affiliated Hospital & Research Academy of Reproductive Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. FAU - Hu, Yuanyuan AU - Hu Y AD - Department of Anesthesiology, The 2nd Affiliated Hospital & Research Academy of Reproductive Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. FAU - Li, Junwei AU - Li J AD - Department of Anesthesiology, The 2nd Affiliated Hospital & Research Academy of Reproductive Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Department of Pharmacology, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. FAU - Hu, Guoxin AU - Hu G AD - Department of Pharmacology, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. FAU - Lian, Qingquan AU - Lian Q AD - Department of Anesthesiology, The 2nd Affiliated Hospital & Research Academy of Reproductive Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. Electronic address: lianqingquanmz@163.com. FAU - Ge, Ren-Shan AU - Ge RS AD - Center of Scientific Research, The 2nd Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Department of Anesthesiology, The 2nd Affiliated Hospital & Research Academy of Reproductive Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. Electronic address: r_ge@yahoo.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141122 PL - Netherlands TA - Toxicol Lett JT - Toxicology letters JID - 7709027 RN - 0 (Desmin) RN - 0 (Phthalic Acids) RN - 0 (Plasticizers) RN - 3XMK78S47O (Testosterone) RN - 4010KIX4CK (diisononyl phthalate) RN - EC 1.1.- (3-Hydroxysteroid Dehydrogenases) SB - IM MH - 3-Hydroxysteroid Dehydrogenases/metabolism MH - Animals MH - Desmin/metabolism MH - Female MH - Gene Expression/drug effects MH - Gonadal Dysgenesis/*chemically induced/pathology MH - Leydig Cells/drug effects MH - Male MH - Phthalic Acids/*toxicity MH - Plasticizers/*toxicity MH - Pregnancy MH - Rats MH - Rats, Sprague-Dawley MH - Testis/drug effects MH - Testosterone/metabolism OTO - NOTNLM OT - Diisononyl phthalate OT - Fetal Leydig cell OT - Gonocyte multinucleation OT - Leydig cell aggregation OT - Testicular dysgenesis EDAT- 2014/12/03 06:00 MHDA- 2015/04/30 06:00 CRDT- 2014/12/03 06:00 PHST- 2014/08/26 00:00 [received] PHST- 2014/11/15 00:00 [revised] PHST- 2014/11/21 00:00 [accepted] PHST- 2014/12/03 06:00 [entrez] PHST- 2014/12/03 06:00 [pubmed] PHST- 2015/04/30 06:00 [medline] AID - S0378-4274(14)01476-3 [pii] AID - 10.1016/j.toxlet.2014.11.024 [doi] PST - ppublish SO - Toxicol Lett. 2015 Jan 22;232(2):466-74. doi: 10.1016/j.toxlet.2014.11.024. Epub 2014 Nov 22.