Ma Mingyue, Kondo Tomoko, Ban Susumu, Umemura Tomohiro, Kurahashi Norie, Takeda Makoto, Kishi Reiko
Department of Public Health, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, Japan.
Toxicol Sci. 2006 Sep;93(1):164-71. doi: 10.1093/toxsci/kfl036. Epub 2006 Jun 8.
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.
我们评估了吸入邻苯二甲酸二（2-乙基己基）酯（DEHP）对青春期前雌性大鼠青春期启动及青春期后生殖功能的影响。从出生后第22天至41天以及至第84天，将雌性大鼠分为几组，以0、5和25毫克/立方米的剂量每天6小时、每周连续5天通过吸入给予DEHP。通过每日检查阴道开口（VO）和首次发情周期来确定青春期启动。通过观察出生后第49天至84天的发情周期来评估生殖功能。暴露结束后，在动情间期于出生后第42天以及出生后第85 - 88天处死大鼠。DEHP暴露使VO年龄和首次发情周期提前，并且在25毫克/立方米DEHP组中血清胆固醇、促黄体生成素和雌二醇水平显著升高。在暴露于DEHP的大鼠中更频繁地观察到不规则发情周期，并且成年期暴露于DEHP的大鼠血清胆固醇降低；逆转录聚合酶链反应（RT-PCR）显示，在25毫克/立方米DEHP组中，编码催化睾酮转化为雌二醇的限速酶的芳香化酶mRNA表达升高。这些数据表明，吸入DEHP可能会提前青春期启动并改变青春期后生殖功能。
