Bodensteiner K J, Sawyer H R, Moeller C L, Kane C M, Pau K-Y F, Klinefelter G R, Veeramachaneni D N R
Animal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523-1683, USA.
Toxicol Sci. 2004 Jul;80(1):83-91. doi: 10.1093/toxsci/kfh135. Epub 2004 May 12.
To determine if dibromoacetic acid (DBA) affects ovarian folliculogenesis, four groups of female Dutch-belted rabbits were exposed daily to 0, 1, 5, or 50 mg DBA/kg body weight in drinking water beginning in utero from gestation day 15 throughout life. Functionality of the endocrine axis was assessed by measuring serum concentrations of gonadotropins following an im injection of 10 microg GnRH at 12 (prepubertal; n = 6/dose group) and 24 (postpubertal; n = 10/dose group) weeks of age. A day after GnRH challenge, number of ovulation sites and ovarian weights were determined at necropsy. Left ovaries were processed for histopathology, serially sectioned at 6 microm, and every twelfth section stained with hematoxylin and eosin was evaluated. All healthy follicles were categorized as primordial, primary, small preantral, large preantral, or small antral follicles. The area of each section evaluated was measured and the number of follicles in each category expressed per mm2 unit area. In prepubertal animals, DBA caused a reduction in number of primordial follicles (p < 0.05) and total healthy follicles (p < 0.05) at 50 mg/kg dose level. In adult animals, there were fewer primordial follicles in both the 5 (p < 0.01) and 50 (p = 0.1) mg/kg dose groups. No profound changes in gonadotropin profiles were observed. Although chronic exposure to DBA did not appear to have an effect on late follicular development or ovulation, DBA did reduce the population of primordial follicles. The long-term health consequences of diminished primordial follicles are unknown, but it is very likely that reproductive senescence would occur earlier.
为了确定二溴乙酸(DBA)是否影响卵巢卵泡发生,将四组雌性荷兰带兔从妊娠第15天开始在子宫内直至终生每日经饮水给予0、1、5或50 mg DBA/kg体重。在12周龄(青春期前;每组n = 6)和24周龄(青春期后;每组n = 10)时,通过肌肉注射10 μg促性腺激素释放激素(GnRH)后测量血清促性腺激素浓度来评估内分泌轴的功能。GnRH激发后一天,在尸检时确定排卵点数量和卵巢重量。将左侧卵巢进行组织病理学处理,连续切片,厚度为6微米,对每十二张苏木精和伊红染色的切片进行评估。所有健康卵泡分为原始卵泡、初级卵泡、小窦前卵泡、大窦前卵泡或小窦卵泡。测量每个评估切片的面积,并以每平方毫米单位面积表示每个类别中的卵泡数量。在青春期前动物中,50 mg/kg剂量水平的DBA导致原始卵泡数量(p < 0.05)和总健康卵泡数量(p < 0.05)减少。在成年动物中,5 mg/kg(p < 0.01)和50 mg/kg(p = 0.1)剂量组的原始卵泡数量均较少。未观察到促性腺激素水平有显著变化。虽然长期接触DBA似乎对卵泡后期发育或排卵没有影响,但DBA确实减少了原始卵泡的数量。原始卵泡减少对长期健康的影响尚不清楚,但很可能生殖衰老会更早发生。