title: Inutero exposure to diisononyl phthalate caused testicular dysgenesis of rat fetal testis.
abstract: 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 3β-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.
authors.affiliation: Center of Scientific Research, The 2nd Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Linxi
authors.initials: L
authors.lastname: Li
authors.affiliation: Center of Scientific Research, The 2nd Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Tiao
authors.initials: T
authors.lastname: Bu
authors.affiliation: Department of Anesthesiology, The 2nd Affiliated Hospital & Research Academy of Reproductive Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Huina
authors.initials: H
authors.lastname: Su
authors.affiliation: Department of Anesthesiology, The 2nd Affiliated Hospital & Research Academy of Reproductive Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Zhichuan
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, The 2nd Affiliated Hospital & Research Academy of Reproductive Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Yuyuan
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Anesthesiology, The 2nd Affiliated Hospital & Research Academy of Reproductive Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Gaolong
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The 2nd Affiliated Hospital & Research Academy of Reproductive Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Danyan
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, The 2nd Affiliated Hospital & Research Academy of Reproductive Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Shan
authors.affiliation: Department of Anesthesiology, The 2nd Affiliated Hospital & Research Academy of Reproductive Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Renai
authors.initials: R
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, The 2nd Affiliated Hospital & Research Academy of Reproductive Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Junwei
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Guoxin
authors.initials: G
authors.lastname: Hu
authors.affiliation: Department of Anesthesiology, The 2nd Affiliated Hospital & Research Academy of Reproductive Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. Electronic address: lianqingquanmz@163.com.
authors.forename: Qingquan
authors.initials: Q
authors.lastname: Lian
authors.affiliation: 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.
authors.forename: Ren-Shan
authors.initials: RS
authors.lastname: Ge
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000818:Animals; D003893:Desmin / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006059:Gonadal Dysgenesis / Q000139:chemically induced* / Q000473:pathology; D007985:Leydig Cells / Q000187:drug effects; D008297:Male; D010795:Phthalic Acids / Q000633:toxicity*; D010968:Plasticizers / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000187:drug effects; D013739:Testosterone / Q000378:metabolism
chemical_list: D003893:Desmin; D010795:Phthalic Acids; D010968:Plasticizers; D013739:Testosterone; C012125:diisononyl phthalate; D015096:3-Hydroxysteroid Dehydrogenases
keywords: Diisononyl phthalate; Fetal Leydig cell; Gonocyte multinucleation; Leydig cell aggregation; Testicular dysgenesis