HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 73/5/908    most recent biolreprod.105.042382v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Thompson, C. J. Articles by Gaido, K. W. Search for Related Content PubMed PubMed Citation Articles by Thompson, C. J. Articles by Gaido, K. W. Agricola Articles by Thompson, C. J. Articles by Gaido, K. W.

Differential Steroidogenic Gene Expression in the Fetal Adrenal Gland Versus the Testis and Rapid and Dynamic Response of the Fetal Testis to Di(n-butyl) Phthalate¹

CIIT Centers for Health Research,³ Research Triangle Park, North Carolina 27709 Sanofi-Aventis Pharmaceuticals,⁴ Bridgewater, New Jersey 08807 National Institute for Statistical Sciences,⁵ Research Triangle Park, North Carolina 27709

The phthalate ester di(n-butyl) phthalate (DBP) causes feminization of male rats upon in utero exposure by repressing expression of genes required for testicular steroidogenesis. Previous work in our laboratory has shown that repression of gene expression and steroidogenesis in the fetal testis is apparent within a few hours of DBP exposure. The purpose of this study was to determine the precise timing of DBP-associated gene expression changes in the fetal testis using transcriptional profiling and to determine whether DBP exerts similar effects on steroidogenesis in the fetal adrenal. A DBP time-course experiment showed that testicular steroidogenesis was decreased within 1 h of DBP exposure and that this decrease preceded the repressed transcription of Star (steroidogenic acute regulatory protein); Scarb1 (scavenger receptor class B, member 1; also know as Sr-b1); Cyp11a1 (cytochrome P450, family 11, subfamily a, polypeptide 1; also known as P450_SCC); and Cyp17a1 (cytochrome P450 family 17, subfamily a, polypeptide 1; also known as Cyp17). Gene expression profiling demonstrated rapid (within 1 to 3 h) and transient induction of immediate early genes in the fetal testis after administration of DBP to the pregnant dam. There was a statistically insignificant decrease in corticosterone production by the fetal adrenal after in utero exposure to DBP from Gestation Day 12 to Gestation Day 19. The extent of steroidogenesis diminution was much less in the adrenal than in the testis (approximately 45% decrease in the adrenal versus 87% decrease in the testis) and expression of genes required for steroidogenesis in the adrenal was unaffected by DBP. Together, these studies demonstrate that DBP initiates a rapid and dynamic change in gene expression in the fetal testis that likely plays a role in the reduction in steroidogenesis that is unique to the fetal testis relative to the steroidogenically active fetal adrenal.

adrenal, adrenal gland, cholesterol, Cyp11a1 (P450_SCC), Cyp17a1, fetal development, male reproduction, male reproductive tract, phthalate esters, reproductive development, scavenger receptor, Steroid acute regulatory protein (Star), steroidogenesis, testis, testosterone, toxicology

² Correspondence: Kevin W. Gaido, CIIT Centers for Health Research, P.O. Box 12137, Research Triangle Park, NC 27709. FAX: 919 558 1300; gaido{at}ciit.org

This article has been cited by other articles:

				K. J. Johnson, S. M. McCahan, X. Si, L. Campion, R. Herrmann, and J. S. Barthold The orl Rat with Inherited Cryptorchidism Has Increased Susceptibility to the Testicular Effects of In Utero Dibutyl Phthalate Exposure Toxicol. Sci., October 1, 2008; 105(2): 360 - 367. [Abstract] [Full Text] [PDF]

				A. J. Kuhl, S. M. Ross, and K. W. Gaido CCAAT/Enhancer Binding Protein {beta}, But Not Steroidogenic Factor-1, Modulates the Phthalate-Induced Dysregulation of Rat Fetal Testicular Steroidogenesis Endocrinology, December 1, 2007; 148(12): 5851 - 5864. [Abstract] [Full Text] [PDF]

				K. J Johnson, J. B Hensley, M. D Kelso, D. G Wallace, and K. W Gaido Mapping Gene Expression Changes in the Fetal Rat Testis Following Acute Dibutyl Phthalate Exposure Defines a Complex Temporal Cascade of Responding Cell Types Biol Reprod, December 1, 2007; 77(6): 978 - 989. [Abstract] [Full Text] [PDF]

				S. Plummer, R. M. Sharpe, N. Hallmark, I. K. Mahood, and C. Elcombe Time-Dependent and Compartment-Specific Effects of In Utero Exposure to Di(n-butyl) Phthalate on Gene/Protein Expression in the Fetal Rat Testis as Revealed by Transcription Profiling and Laser Capture Microdissection Toxicol. Sci., June 1, 2007; 97(2): 520 - 532. [Abstract] [Full Text] [PDF]

				D. Pignatelli, F. Xiao, A. M Gouveia, J. G Ferreira, and G. P Vinson Adrenarche in the rat. J. Endocrinol., October 1, 2006; 191(1): 301 - 308. [Abstract] [Full Text] [PDF]

				S. A. Lahousse, D. G. Wallace, D. Liu, K. W. Gaido, and K. J. Johnson Testicular Gene Expression Profiling following Prepubertal Rat Mono-(2-ethylhexyl) Phthalate Exposure Suggests a Common Initial Genetic Response at Fetal and Prepubertal Ages Toxicol. Sci., October 1, 2006; 93(2): 369 - 381. [Abstract] [Full Text] [PDF]

				D. V. Henley and K. S. Korach Endocrine-Disrupting Chemicals Use Distinct Mechanisms of Action to Modulate Endocrine System Function Endocrinology, June 1, 2006; 147(6): s25 - s32. [Abstract] [Full Text] [PDF]

				P Froment, F Gizard, D Defever, B Staels, J Dupont, and P Monget Peroxisome proliferator-activated receptors in reproductive tissues: from gametogenesis to parturition. J. Endocrinol., May 1, 2006; 189(2): 199 - 209. [Abstract] [Full Text] [PDF]

				R. M. David Proposed Mode of Action for In Utero Effects of Some Phthalate Esters on the Developing Male Reproductive Tract Toxicol Pathol, April 1, 2006; 34(3): 209 - 219. [Abstract] [Full Text] [PDF]