Perinatal exposure of female rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin induces central precocious puberty in the offspring

Perinatal exposure of female rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin induces central precocious puberty in the offspring
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DOI:
10.1677/joe-08-0062
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发表时间:
2008-05-01
影响因子:
4
通讯作者:
Tohyama, Chiharu
Tohyama, Chiharu
中科院分区:
医学2区
文献类型:
--
作者:
Kakeyama, Masaki;Sone, Hideko;Tohyama, Chiharu

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在胎儿和新生儿时期暴露于2,3,7,8-四氯二苯并-对-二恶英(TCED)已被证明会改变后代以后的发育。在这项研究中,我们确定围产期暴露于低剂量的TCDD是否会影响Long-Evans hooded大鼠雌性后代的青春期开始。在妊娠第15天,妊娠雌性大鼠通过管饲法以0(溶剂)、200或800 ng/kg b. xv的单次剂量给予TCDD。在母鼠以200或800 ng/kg b.w.剂量给予TCDD后所生的雌性后代中,阴道张开和第一次发情比赋形剂处理的动物所生的后代早4-7天发生。卵巢重量增加也加速后,暴露于TCDD的剂量依赖性方式。接下来,我们检查了卵巢代偿性肥大(OCH)作为垂体和下丘脑中LH/GnRH产生系统成熟的指标。暴露于TCDD加速发病OCH的雌性后代在剂量依赖性的方式。特别是,暴露于800 ng/kg b.w.四氯二苯并对二恶英的母鼠所生的后代。在出生后第27-30天观察到肥大,其特征在于超排卵和半卵巢切除术后剩余卵巢重量的显著增加,这比赋形剂处理的母鼠所生的后代早10天。这些结果表明,围产期暴露于低剂量的TCDD诱导性早熟,包括早熟的下丘脑-垂体轴,性腺和生殖器,在雌性Long-Evans hooded大鼠。
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCED) during the fetal and neonatal periods has been indicated to alter the development of the offspring later in life. In this study, we determined whether perinatal exposure to a low dose of TCDD affects the onset of puberty in the female offspring of Long-Evans hooded rats. On day 15 of gestation, pregnant female rats were administered TCDD by gavage at a single dose of 0 (vehicle), 200, or 800 ng/kg b.xv. In the female offspring born to dams administered with TCDD at either 200 or 800 ng/kg b.w. the vaginal opening and first estrus occurred similar to 4-7 days earlier than in the offspring born to vehicle-treated animals. The ovarian weight gain was also accelerated following exposure to TCDD in a dose-dependent manner. We next examined the ovarian compensatory hypertrophy (OCH) as an indicator of the maturation of the LH/GnRH-generating system in the pituitary and the hypothalamus. Exposure to TCDD accelerated the onset of OCH in the female offspring in a dose-dependent manner. In particular, in the offspring born to the dams exposed to TCDD at 800 ng/kg b.w. hypertrophy, which is characterized by hyperovulation and a marked increase in the weight of the remaining ovary after hemi-ovariectomy, was observed on postnatal days 27-30, which was 10 days earlier than in the offspring born to the vehicle-treated dams. These results indicate that perinatal exposure to a low dose of TCDD induces precocious puberty, including early maturation of the hypothalamic-pituitary axis, the gonads and genitals, in female Long-Evans hooded rats.