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ToxSci Advance Access originally published online on June 8, 2006
Toxicological Sciences 2006 93(1):164-171; 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

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

Mingyue Ma1, Tomoko Kondo, Susumu Ban, Tomohiro Umemura, Norie Kurahashi, Makoto Takeda and Reiko Kishi

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

Received April 24, 2006; accepted June 1, 2006

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 h/day, 5 contiguous days/week from postnatal days (PNDs) 22 to 41 and to PND 84. The onset of puberty was determined by daily examination for vaginal opening (VO) and first estrous cycle. Reproductive function was evaluated by observing estrous cyclicity from PNDs 49 to 84. Upon completion of exposure, the rats were sacrificed at PND 42 and PNDs 85–88 during the diestrous stage. DEHP exposure advanced the age of VO and first estrous cycle, and serum cholesterol, luteinizing hormone, 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 the onset of puberty and alter postpubertal reproductive functions.

Key Words: DEHP; female; reproductive functions; inhalation.


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