Skip Navigation


ToxSci Advance Access originally published online on May 2, 2003
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Tables
Right arrow All Versions of this Article:
74/1/114    most recent
kfg096v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (16)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Turner, K. J.
Right arrow Articles by Foster, P. M. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Turner, K. J.
Right arrow Articles by Foster, P. M. D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Toxicological Sciences 74, 114-128 (2003)
Copyright © 2003 by the 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

Katie J. Turner1, Barry S. McIntyre2, Suzanne L. Phillips, Norman J. Barlow2, Christopher J. Bowman and Paul M. D. Foster2

CIIT Centers for Health Research, Research Triangle Park, North Carolina 27709-2137

Linuron is an herbicide with weak androgen receptor (AR) antagonist activity. Exposure to linuron from gestation days (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 receptors 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.

Key Words: linuron; androgen receptor antagonist; Wolffian duct development; epididymis.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
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]

Home page
 EndocrinologyHome page
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]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
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]

Home page
 EndocrinologyHome page
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]

Home page
 EndocrinologyHome page
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]

Home page
 EndocrinologyHome page
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]

Home page
 J EndocrinolHome page
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]

Home page
 Toxicol SciHome page
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]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.