ToxSci Advance Access published online on May 2, 2003
Toxicological Sciences, doi:10.1093/toxsci/kfg096
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 CIIT Centers for Health Research, Research Triangle Park, North Carolina 27709-2137, USA
* To whom correspondence should be addressed. E-mail: katie_turner{at}merck.com.
Linuron is a herbicide with weak androgen receptor (AR) antagonist activity. Exposure to linuron from gestation day (GD) 12 to 21 perturbs androgen-dependent male reproductive development. In utero exposure to 50 mg/kg/day linuron induces malformations of the epididymis and the vas deferens. The objective of this study was to identify alterations in gene expression within the testis and epididymis associated with abnormal Wolffian duct development and to correlate changes in gene expression with the gross morphology of the affected epididymides. Pregnant Sprague-Dawley rats were administered either corn oil vehicle or linuron (50 mg/kg/day) by gavage from GD 12 to 21 (n=3-6 controls, n=5-10 linuron-treated dams per time point). Changes in gene expression were evaluated in testes on GD 21 and in epididymides on GD 21 and postnatal day (PND) 7 using cDNA microarrays and confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) analyses. RNA was isolated from intact epididymides with reduced or no ductal coiling from the linuron groups, and epididymides with noncontiguous ducts were excluded. In the fetal testis, exposure to linuron did not result in reduced mRNA expression of the AR or that of several steroidogenic enzymes, supporting the hypothesis that linuron does not reduce fetal testosterone production. Linuron induced a significant decrease in AR mRNA expression in GD 21 epididymides. Significant changes in mRNA expression in GD 21 and PND 7 epididymides were also identified in the epidermal growth factor (EGF), insulin-like growth factor 1 (IGF-1), bone morphogenetic protein (BMP), fibroblast growth factor (FGF), and Notch signaling pathways. These pathways are involved in tissue morphogenesis. Changes in the expression of AR and IGF-1 receptor were detected by immunostaining in malformed epididymides from linuron-exposed rats. Linuron induced changes in epididymal gene expression suggestive of altered paracrine interactions between the mesenchyme and epithelial cells during development. The EGF, Notch, IGF-1, BMP4, and FGF signaling pathways may be involved in normal testosterone-mediated development of the Wolffian duct.
© 2003 Society of Toxicology
Reproductive and Developmental Toxicology
Altered Gene Expression During Rat Wolffian Duct Development in Response to in Utero Exposure to the Antiandrogen Linuron
2 National Institutue of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Tomaszewski, A. Joseph, D. Archambeault, and H. H.-C. Yao Essential roles of inhibin beta A in mouse epididymal coiling PNAS, July 3, 2007; 104(27): 11322 - 11327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Welsh, P. T. K. Saunders, and R. M. Sharpe The Critical Time Window for Androgen-Dependent Development of the Wolffian Duct in the Rat Endocrinology, July 1, 2007; 148(7): 3185 - 3195. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Tian, N. Washizawa, L. H. Gu, M. S. Levin, L. Wang, D. C. Rubin, S. Mwangi, S. Srinivasan, Y. Gao, D. P. Jones, et al. Stimulation of colonic mucosal growth associated with oxidized redox status in rats Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2007; 292(3): R1081 - R1091. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Anway, C. Leathers, and M. K. Skinner Endocrine Disruptor Vinclozolin Induced Epigenetic Transgenerational Adult-Onset Disease Endocrinology, December 1, 2006; 147(12): 5515 - 5523. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-S. Chang, M. D. Anway, S. S. Rekow, and M. K. Skinner Transgenerational Epigenetic Imprinting of the Male Germline by Endocrine Disruptor Exposure during Gonadal Sex Determination Endocrinology, December 1, 2006; 147(12): 5524 - 5541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Welsh, P. T. K. Saunders, N. I. Marchetti, and R. M. Sharpe Androgen-Dependent Mechanisms of Wolffian Duct Development and Their Perturbation by Flutamide Endocrinology, October 1, 2006; 147(10): 4820 - 4830. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. A. Henderson, G. M Cooke, and B. Robaire Region-specific expression of androgen and growth factor pathway genes in the rat epididymis and the effects of dual 5{alpha}-reductase inhibition. J. Endocrinol., September 1, 2006; 190(3): 779 - 791. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Bowman, K. J. Turner, M. Sar, N. J. Barlow, K. W. Gaido, and P. M. D. Foster Altered Gene Expression During Rat Wolffian Duct Development following Di(n-Butyl) Phthalate Exposure Toxicol. Sci., July 1, 2005; 86(1): 161 - 174. [Abstract] [Full Text] [PDF]
|
|