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Abstract

Transgenerational effects of environmental toxins require either a chromosomal or epigenetic alteration in the germ line. Transient exposure of a gestating female rat during the period of gonadal sex determination to the endocrine disruptors vinclozolin (an antiandrogenic compound) or methoxychlor (an estrogenic compound) induced an adult phenotype in the F1 generation of decreased spermatogenic capacity (cell number and viability) and increased incidence of male infertility. These effects were transferred through the male germ line to nearly all males of all subsequent generations examined (that is, F1 to F4). The effects on reproduction correlate with altered DNA methylation patterns in the germ line. The ability of an environmental factor (for example, endocrine disruptor) to reprogram the germ line and to promote a transgenerational disease state has significant implications for evolutionary biology and disease etiology.
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References and Notes

1
V. Rakyan, E. Whitelaw, Curr. Biol.13, R6 (2003).
2
R. Barber, M. A. Plumb, E. Boulton, I. Roux, Y. E. Dubrova, Proc. Natl. Acad. Sci. U.S.A.99, 6877 (2002).
3
I. D. Morris, Int. J. Androl.25, 255 (2002).
4
C. M. Foran, B. N. Peterson, W. H. Benson, Toxicol. Sci.68, 389 (2002).
5
C. DeRosa, P. Richter, H. Pohl, D. E. Jones, J. Toxicol. Environ. Health B Crit. Rev.1, 3 (1998).
6
V. K. Rakyan et al., Proc. Natl. Acad. Sci. U.S.A.100, 2538 (2003).
7
P. Hajkova et al., Mech. Dev.117, 15 (2002).
8
G. Durcova-Hills, J. Ainscough, A. McLaren, Differentiation68, 220 (2001).
9
W. Reik, J. Walter, Nat. Rev. Genet.2, 21 (2001).
10
A. Jost, S. Magre, R. Agelopoulou, Hum. Genet.58, 59 (1981).
11
M. Buehr, S. Gu, A. McLaren, Development117, 273 (1993).
12
G. Majdic, M. R. Millar, P. T. Saunders, J. Endocrinol.147, 285 (1995).
13
H. O. Goyal et al., Anat. Rec.249, 54 (1997).
14
W. R. Kelce, E. Monosson, M. P. Gamcsik, S. C. Laws, L. E. Gray Jr., Toxicol. Appl. Pharmacol.126, 276 (1994).
15
A. M. Cummings, Crit. Rev. Toxicol.27, 367 (1997).
16
K. W. Gaido et al., Endocrinology140, 5746 (1999).
17
W. R. Kelce, C. R. Lambright, L. E. Gray Jr., K. P. Roberts, Toxicol. Appl. Pharmacol.142, 192 (1997).
18
J. S. Fisher, Reproduction127, 305 (2004).
19
R. E. Chapin et al., Fundam. Appl. Toxicol.40, 138 (1997).
20
A. S. Cupp et al., J. Androl.24, 736 (2003).
21
M. Uzumcu, H. Suzuki, M. K. Skinner, Reprod. Toxicol.18, 765 (2004).
22
B. S. Shi, Z. N. Cai, J. Yang, Y. N. Yu, Mutat. Res.556, 1 (2004).
23
H. Dong et al., Biochemistry43, 15922 (2004).
24
A. Tokumura, J. Cell. Biochem.92, 869 (2004).
25
We acknowledge the technical contributions of I. Sadler-Riggleman, S. Rekow, and B. Johnston and the assistance of H. Suzuki with the methylation PCR procedure. This research was supported in part by a grant to M.K.S. from the U.S. Environmental Protection Agency's Science to Achieve Results (STAR) program involving endocrine disruptors.

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Published In

Science
Volume 308Issue 57273 June 2005
Pages: 1466 - 1469
PubMed: 15933200

History

Received: 2 December 2004
Accepted: 22 March 2005

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Authors

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Matthew D. Anway
Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, WA 99164–4231, USA.
Andrea S. Cupp*
Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, WA 99164–4231, USA.
Mehmet Uzumcu
Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, WA 99164–4231, USA.
Michael K. Skinner
Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, WA 99164–4231, USA.

Notes

‡ To whom correspondence should be addressed. E-mail: [email protected]

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Science
Volume 308|Issue 5727
3 June 2005
Submission history
Received:2 December 2004
Accepted:22 March 2005
Published in print:3 June 2005
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