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ToxSci Advance Access originally published online on December 26, 2006
Toxicological Sciences 2007 96(2):218-226; doi:10.1093/toxsci/kfl196
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Perspectives: The Possible Influence of Assisted Reproductive Technologies on Transgenerational Reproductive Effects of Environmental Endocrine Disruptors

Thomas M. Price*,1, Susan K. Murphy{dagger} and Edward V. Younglai{ddagger}

* Division of Reproductive Endocrinology {dagger} Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University, Durham, North Carolina 27710 {ddagger} Department of Obstetrics and Gynecology, Reproductive Biology Division, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada L8N 3Z5

1 To whom correspondence should be addressed at 5704 Fayetteville Road, Durham, NC 27713. Fax: (919) 484-0461. E-mail: price067{at}mc.duke.edu.

Received September 27, 2006; accepted December 21, 2006


  Abstract

Demasculinization by environmental endocrine-disrupting chemicals (EDCs) is observed in many animal species but less evident in humans. Rodent studies with gestational exposure to either the fungicide vinclozolin or the insecticide methoxychlor demonstrate impaired male fertility with abnormal DNA methylation patterns in spermatozoa. Once established, these epigenetic changes may be permanent and thus paternally passed to subsequent generations. Conclusive evidence of a similar phenomenon in humans has not been established, but several observations bring up the possibility. Some, but not all, studies show an increase in male genital abnormalities after prenatal EDC exposure. Other studies demonstrate sperm abnormalities in males with EDC contact, although it is unclear as to whether this is due to prenatal or postnatal exposure. Although not examined in males with EDC exposure, one study shows gamete DNA methylation abnormalities in males with severe oligospermia. A subsequent study failed to corroborate these findings. The use of assisted reproductive techniques including intracytoplasmic sperm injection has removed natural selection barriers thus enabling reproduction in males that would otherwise be sterile. This review explores the hypothesis that prenatal EDC exposure results in transgenerational male reproductive abnormalities propagated by the use of assisted reproductive technologies.

Key Words: endocrine-disrupting chemicals; DNA methylation; imprinting; assisted reproductive technologies; intracytoplasmic sperm injection.


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