Department of Animal Science, University of California, Davis, CA 95616-8521, USA.
Toxicol Sci. 2011 Feb;119(2):380-90. doi: 10.1093/toxsci/kfq337. Epub 2010 Nov 8.
In this study, we quantified the effects of in utero exposure to the herbicide atrazine on subsequent mammary gland development. Atrazine was administered to pregnant female Long Evans rats from gestation days 13-19 at doses of 0, 6.5, 50, or 100 mg/kg/day. A pair-fed control group was yoked to the high-dose atrazine-treated group. Litter size was standardized to 10 pups on postnatal day (PND) 4. Whole mounts of the left fourth mammary gland and histologic sections of the right fourth gland were obtained from a subgroup of offspring on PND1, 21, 33, on day of vaginal opening (VO), or around PND65 at diestrus. A blinded, quantitative analysis of key morphological features in mammary gland whole mounts (ductal elongation, ductal network area, epithelial area, terminal end bud [TEB] incidence, and epithelial density) as well as epithelial proliferation within different parenchymal structures was conducted. There was no effect of atrazine exposure on any of the measures of mammary gland development at the maternal dose of 6.5 mg/kg/day. On PND1, ductal elongation was increased by approximately 20% (p < 0.05) in the female offspring born to dams exposed to 50 and 100 mg/kg/day atrazine, coincident with decreased epithelial proliferation in the 100 mg/kg/day group at this age. These differences were not present on PND21, or thereafter. An increased incidence of TEB in the mammary glands from females that were born to both the pair-fed and 50 mg/kg/day-treated dams at the time of VO indicated that this response was a specific result of maternal caloric restriction. Collectively, these data indicate that maternal atrazine exposure has no long-term effects on mammary gland development in female offspring beyond a transitory response to high doses at PND1.
在这项研究中，我们定量评估了孕期暴露于除草剂莠去津对随后乳腺发育的影响。从妊娠第 13 天到第 19 天，给怀孕的 Long Evans 大鼠喂食莠去津，剂量分别为 0、6.5、50 或 100mg/kg/天。一组配对喂食的对照组与高剂量莠去津处理组相匹配。产后第 4 天（PND），每组 10 只幼崽。从小鼠 PND1、21、33、阴道开口（VO）当天或发情期（PND65 左右）获得左第四乳腺的全乳标本和右第四乳腺的组织学切片。对乳腺全乳标本（导管伸长、导管网络面积、上皮面积、终末芽（TEB）发生率和上皮密度）以及不同实质结构内上皮增殖的关键形态特征进行盲法、定量分析。在母体 6.5mg/kg/天的莠去津暴露剂量下，没有观察到乳腺发育的任何指标受到莠去津暴露的影响。在 PND1，50 和 100mg/kg/天莠去津处理组的母鼠所生雌性后代的导管伸长增加了约 20%（p<0.05），同时在这个年龄组的 100mg/kg/天组中上皮增殖减少。在 PND21 或之后，这些差异并不存在。在 VO 时，来自配对喂食和 50mg/kg/天处理组母鼠所生雌性后代的乳腺 TEB 发生率增加，表明这种反应是母体热量限制的特定结果。总的来说，这些数据表明，母体莠去津暴露对雌性后代乳腺发育没有长期影响，超过了 PND1 时高剂量的短暂反应。
