title: Effects of in Utero Exposure to Dicyclohexyl Phthalate on Rat Fetal Leydig Cells.
abstract: Dicyclohexyl phthalate (DCHP) is one of the phthalate plasticizers. The objective of the present study was to investigate the effects of DCHP on fetal Leydig cell distribution and function as well as testis development. Female pregnant Sprague Dawley dams orally received vehicle (corn oil, control) or DCHP (10, 100, and 500 mg/kg/day) from gestational day (GD) 12 to GD 21. At GD 21.5, testicular testosterone production, fetal Leydig cell number and distribution, testicular gene and protein expression levels were examined. DCHP administration produced a dose-dependent increase of the incidence of multinucleated gonocytes at ≥ 100 mg/kg. DCHP dose-dependently increased abnormal fetal Leydig cell aggregation and decreased fetal Leydig cell size, cytoplasmic size, and nuclear size at ≥ 10 mg/kg. DCHP reduced the expression levels of steroidogenesis-related genes (including Star, Hsd3b1, and Hsd17b3) and testis-descent related gene Insl3 as well as protein levels of 3β-hydroxysteroid dehydrogenase 1 (HSD3B1) and insulin-like 3 (INSL3) at ≥ 10 mg/kg. DCHP significantly inhibited testicular testosterone levels at ≥ 100 mg/kg. The results indicate that in utero exposure to DCHP affects the expression levels of fetal Leydig cell steroidogenic genes and results in the occurrence of multinucleated gonocytes and Leydig cell aggregation.
authors.affiliation: The Second Affiliated Hospital &amp; Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China. yaoyao_0111@126.com.
authors.forename: Xiaoheng
authors.initials: X
authors.lastname: Li
authors.affiliation: The Second Affiliated Hospital &amp; Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China. xminch@163.com.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325000, China. hgx@wzmc.edu.cn.
authors.forename: Guoxin
authors.initials: G
authors.lastname: Hu
authors.affiliation: The Second Affiliated Hospital &amp; Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China. lilinxi1234@163.com.
authors.forename: Linxi
authors.initials: L
authors.lastname: Li
authors.affiliation: The Second Affiliated Hospital &amp; Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China. suhuina1988@163.com.
authors.forename: Huina
authors.initials: H
authors.lastname: Su
authors.affiliation: The Second Affiliated Hospital &amp; Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China. wyy19880119@163.com.
authors.forename: Yiyan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Second Affiliated Hospital &amp; Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China. gerenshan2@163.com.
authors.forename: Dongxin
authors.initials: D
authors.lastname: Chen
authors.affiliation: The Second Affiliated Hospital &amp; Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China. flower3377@163.com.
authors.forename: Qiqi
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: The Second Affiliated Hospital &amp; Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China. dishboy@163.com.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325000, China. gravity172@gmail.com.
authors.forename: Junwei
authors.initials: J
authors.lastname: Li
authors.affiliation: Taizhou Hospital of Zhejiang Province, Taizhou 317000, China. wangmc@enzemed.com.
authors.forename: Mingcang
authors.initials: M
authors.lastname: Wang
authors.affiliation: The Second Affiliated Hospital &amp; Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China. lianqingquanmz@163.com.
authors.forename: Qingquan
authors.initials: Q
authors.lastname: Lian
authors.affiliation: The Second Affiliated Hospital &amp; Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China. r_ge@yahoo.com.
authors.forename: Ren-Shan
authors.initials: RS
authors.lastname: Ge
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000187:drug effects*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D007985:Leydig Cells / Q000187:drug effects*; D008297:Male; D010795:Phthalic Acids / Q000009:adverse effects*; D010968:Plasticizers / Q000009:adverse effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000187:drug effects* / Q000254:growth & development*; D013739:Testosterone / Q000378:metabolism*
chemical_list: D010795:Phthalic Acids; D010968:Plasticizers; D013739:Testosterone; C032279:phthalic acid
keywords: Leydig cell aggregation; dicyclohexyl phthalate; fetal Leydig cell; testosterone