This Article Free Full Text (Free PDF) Free References 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 Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Barlow, N. J. Articles by Foster, P. M.D. Search for Related Content PubMed PubMed Citation Articles by Barlow, N. J. Articles by Foster, P. M.D. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB DIBUTYL PHTHALATE Social Bookmarking                         What's this?

Pathogenesis of Male Reproductive Tract Lesions from Gestation Through Adulthood Following in Utero Exposure to Di(n-butyl) Phthalate

CT Centers for Health Research, Six Davis Drive, PO Box 12137, Research Triangle Park, North Carolina 27709-2137, USA

Paul M.D. Foster

CT Centers for Health Research, Six Davis Drive, PO Box 12137, Research Triangle Park, North Carolina 27709-2137, USA

Di(n-butyl) phthalate (DBP) acts as an antiandrogen by decreasing fetal testicular testosterone synthesis when male rats are exposed in utero. DBPexposed male rats develop malformations of the reproductive tract secondary to the reduced fetal androgen levels. However, these malformations and the associated histologic lesions have only been described in adult rats. The objective of this study was to describe the male reproductive tract lesions in fetal, early postnatal, and young adult male rats following DBP exposure in utero. Pregnant Sprague-Dawley rats were exposed to 500 mg/kg/day DBP by gavage on gestation days (GD) 12 to 21. Male reproductive tracts were examined on GD 16 to 21 and on postnatal days (PND) 3, 7, 16, 21, 45, and 70. In the fetal testes, large aggregates of Leydig cells, multinucleated gonocytes, and increased numbers of gonocytes were first detected on GD 17 and increased in incidence to 100% by GD 20 and 21. These lesions resolved during the early postnatal period, while decreased numbers of spermatocytes were noted on PND 16 and 21. On PND 45, there was mild degeneration of the seminiferous epithelium, which progressed to severe seminiferous epithelial degeneration on PND 70. On PND 70, the degeneration was concurrent with ipsilateral malformed epididymides, which caused obstruction of testicular fluid flow and secondary pressure atrophy in the seminiferous tubules. In the fetus, the epididymal lesion was observed as decreased coiling of the epididymal duct. The decreased coiling progressed into the early postnatal period and adulthood, at which time malformed epididymides were apparent. As the animals were only dosed in utero, these findings indicate that DBP can initiate fetal testicular and epididymal changes that may not manifest as clear malformations until adulthood. The pathogenesis of lesion development from the fetus to the adult is important for comparison of antiandrogens with differing modes of action.

Key Words: Phthalate • di(n-butyl) • male reproductive development • in utero exposure • reproductive tract malformations • antiandrogen.

Toxicologic Pathology, Vol. 31, No. 4, 397-410 (2003)
DOI: 10.1080/01926230390202335


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				A. Lehraiki, C. Racine, A. Krust, R. Habert, and C. Levacher Phthalates Impair Germ Cell Number in the Mouse Fetal Testis by an Androgen- and Estrogen-Independent Mechanism Toxicol. Sci., October 1, 2009; 111(2): 372 - 382. [Abstract] [Full Text] [PDF]

				C. E. Talsness, A. J. M. Andrade, S. N. Kuriyama, J. A. Taylor, and F. S. vom Saal Components of plastic: experimental studies in animals and relevance for human health Phil Trans R Soc B, July 27, 2009; 364(1526): 2079 - 2096. [Abstract] [Full Text] [PDF]

				G. R Hutchison, H. M Scott, M. Walker, C. McKinnell, D. Ferrara, I. K. Mahood, and R. M Sharpe Sertoli Cell Development and Function in an Animal Model of Testicular Dysgenesis Syndrome Biol Reprod, February 1, 2008; 78(2): 352 - 360. [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]

				P. Howroyd, R. Hoyle-Thacker, O. Lyght, D. Williams, and E. Kleymenova Morphology of the Fetal Rat Testis Preserved in Different Fixatives Toxicol Pathol, February 1, 2005; 33(2): 300 - 304. [Abstract] [Full Text] [PDF]