Malformations In gubernacular ligament development induced by DEHP, DBP, and BBP are associated with decreases in insl3 gene expression in the fetal rat testis
Wilson, VS; Lambright, C; Furr, J; Wood, C; Held, G; Gray, LE
HERO ID
675517
Reference Type
Journal Article
Subtype
Abstract
Year
2004
Language
English
| HERO ID | 675517 |
|---|---|
| Material Type | Abstract |
| In Press | No |
| Year | 2004 |
| Title | Malformations In gubernacular ligament development induced by DEHP, DBP, and BBP are associated with decreases in insl3 gene expression in the fetal rat testis |
| Authors | Wilson, VS; Lambright, C; Furr, J; Wood, C; Held, G; Gray, LE |
| Journal | Toxicologist |
| Volume | 78 |
| Issue | 1S |
| Page Numbers | 282 |
| Abstract | Targeted inactivation of the insulin-like hormone 3 (insl3) gene in male mice results in altered gubernacular development, disrupted testis decent, and cryptorchidism. Cryptorchidism is a fairly common human malformation, being displayed in about 3 males per 100 at birth, but only a small percentage has been linked directly to genetic defects. Recently, concern has arisen over the apparent increase in male reproductive health problems and the potential role of endocrine disrupting chemicals in the etiology of these conditions. The phthalate esters (PE) are high production volume, ubiquitous environmental chemicals, some of which alter sexual differentiation, inducing gubernacular agenesis and other male rat reproductive tract malformations. We hypothesized that phthalate-induced gubernacular lesions likely result from an inhibition of Leydig cell insl3 gene expression. Three phthalates, di-n-ethylhexyl phthalate (DEHP), dibutyl phthalate (DBP) and benzyl butyl phthalate (BBP) were administered orally to the dam (750 mg/kg/day) on gestation day (GD) 14 through 18 and the fetal testes examined on GD18 for effects on steroid hormone production and insl3 gene expression. Compared to chemicals like vinclozolin, linuron, and prochloraz that act as AR antagonists and/or inhibit fetal Leydig cell testosterone production, only the three phthalates significantly reduced both ex vivo testosterone production and insl3 gene expression when quantified by real-time rtPCR. Dose response studies with DEHP (0, 100, 300, 600 or 900 mg/kg/day) also showed a dose dependent decrease in both testicular testosterone production and insl3 message levels in the GD18 rat fetus. These results provide the first demonstration of dose dependent PE-induced alteration of insl3 mRNA in the fetal male rat testis. |
| Is Certified Translation | No |
| Dupe Override | No |
| Conference Location | Baltimore, MD |
| Conference Name | Society of Toxicology 43rd Annual Meeting |
| Conference Date | March 21-25, 2004 |
| Comments | Authoring Organization: EASTMAN KODAK OCC HEALTH LAB |
| Is Public | Yes |
| Language Text | English |
| Keyword | Pregnancy; Rats; Animals; Male; Female; Phthalic Acids/*TOXICITY; Diethylhexyl Phthalate/TOXICITY; Dibutyl Phthalate/TOXICITY; Phthalic Acids/TOXICITY; *Prenatal Exposure Delayed Effects; Gestational Age; Testis/*DRUG EFFECTS/METABOLISM/ABNORMALITIES/EMBRYOLOGY; Urogenital Abnormalities/CHEMICALLY INDUCED/*GENETICS; Gene Expression Regulation, Developmental/*DRUG EFFECTS; Dose-Response Relationship, Drug; NO CAS RN; 117-81-7; 84-74-2; 85-68-7 |
| Is Qa | No |