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ToxSci Advance Access published online on June 8, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl036
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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
Received April 24, 2006
Accepted June 1, 2006

Reproductive and Developmental Toxicology

Exposure of Prepubertal Female Rats to Inhaled di(2-ethylhexyl)phthalate Affects the Onset of Puberty and Postpubertal Reproductive Functions

Mingyue Ma 1 *, Tomoko Kondo 1, Susumu Ban 1, Tomohiro Umemura 1, Norie Kurahashi 1, Makoto Takeda 1, and Reiko Kishi 1

1 Department of Public Heath, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, Japan

* To whom correspondence should be addressed.
Mingyue Ma, E-mail: mamingy{at}med.hokudai.ac.jp


  Abstract

We evaluated the effects of inhaled di(2-ethylhexyl)phthalate (DEHP) on the onset of puberty and on postpubertal reproductive functions in prepubertal female rats. DEHP was administered by inhalation at doses of 0, 5, and 25 mg/m3 to groups of female rats for 6 hr per day, 5 contiguous days per week from postnatal day (PND) 22 to PND 41 and to PND 84. The onset of puberty was determined by daily examination for vaginal opening and first estrous cycle. Reproductive function was evaluated by observing estrous cyclicity from PND 49 to PND 84. Upon completion of exposure, the rats were sacrificed at PND 42 and PND 85-88 during the diestrous stage. DEHP exposure advanced the age of vaginal opening and first estrous cycle, and serum cholesterol, luteinizing hormone (LH) and estradiol levels were significantly elevated in the 25 mg/m3 DEHP group. Irregular estrous cycles were observed more frequently in DEHP-exposed rats, and serum cholesterol decreased in DEHP-exposed rats in adulthood; RT-PCR showed that the expression of aromatase mRNA, encoding a rate-limiting enzyme that catalyzes the conversion of testosterone to estradiol, was elevated in the 25 mg/m3 DEHP group. These data suggest that inhaled DEHP may advance puberty onset and alter postpubertal reproductive functions.

Keywords: DEHP; Female; Reproductive functions; inhalation.
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