Biol Reprod Keystone Symposia Conference on Frontiers in Reproductive Biology & Regulation of Fertility.
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BOR - Papers in Press, published online ahead of print May 18, 2005.
Biol Reprod 2005, 10.1095/biolreprod.104.037184
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BIOLOGY OF REPRODUCTION 73, 482–490 (2005)
DOI: 10.1095/biolreprod.104.037184
© 2005 by the Society for the Study of Reproduction, Inc.

Exposure In Utero to Di(n-Butyl) Phthalate Alters the Vimentin Cytoskeleton of Fetal Rat Sertoli Cells and Disrupts Sertoli Cell-Gonocyte Contact1

Elena Kleymenova 2, 3, Cynthia Swanson 3, Kim Boekelheide 4, and Kevin W. Gaido 3

CIIT Centers for Health Research,3 Research Triangle Park, North Carolina 27709 Brown University,4 Providence, Rhode Island 02912

Di(n-butyl) phthalate (DBP) is commonly used in personal care products and as a plasticizer to soften consumer plastic products. Male rats exposed to DBP in utero have malformations of the male reproductive tract and testicular atrophy characterized by degeneration of seminiferous epithelium and decreased sperm production. In the fetal testis, in utero exposure to DBP reportedly resulted in reduced testosterone levels, Leydig cell aggregates, and multinucleated gonocytes (MNG). We investigated whether exposure in utero to DBP affects rat fetal Sertoli cells and compromises interactions between Sertoli and germ cells in the developing testis. Histological examination showed that MNG occurred at low frequency in the normal fetal rat testis. Exposure in utero at the dose level of DBP above estimated environmental or occupational human exposure levels significantly increased the number of these abnormal germ cells. Postnatally, MNG exhibited aberrant mitoses and were detected at the basal lamina. MNG were not apoptotic in the fetal and postnatal rat testes, as indicated by TUNEL. Sertoli cells in DBP-exposed fetal testis had retracted apical processes, altered organization of the vimentin cytoskeleton, and abnormal cell-cell contacts with gonocytes. The effect of DBP on Sertoli cell morphology at the level of light microscopy was reversed after birth and cessation of exposure. Our data indicate that fetal Sertoli cells are targeted by exposure in utero to DBP and suggest that abnormal interactions between Sertoli and germ cells during fetal life play a role in the development of MNG.

embryo, male sexual function, Sertoli cells, testis, toxicology

1 Supported by the American Chemistry Council's Long-Range Research Initiative, NIH R01 grant ES 05033 (K.B.) and EPA STAR grant R830766 (K.G.). This article does not necessarily reflect the views or policies of these organizations.

2 Correspondence: Elena Kleymenova, CIIT Centers for Health Research, 6 Davis Dr., Research Triangle Park, NC 27709. FAX: 919 558 1300; ekleymenova{at}ciit.org






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Copyright © 2005 by the Society for the Study of Reproduction.