摘要目的:探讨生命早期饮水型砷暴露对雌性小鼠乳腺发育的影响。方法:选取健康、性成熟的C57BL/6J小鼠，按照雌雄比2∶1合笼，确认怀孕后，采用随机数字表法将孕鼠分为对照组（饮用双蒸水）和低、高剂量砷暴露组（饮水砷暴露剂量分别为0.5、5.0 mg/L），每组10只。饮水砷暴露时间从怀孕第0天至仔鼠出生后第28天。砷暴露结束后处死雌性仔鼠，每组10只，剥离乳腺进行全组织染色，评价仔鼠的乳腺发育情况，并进行乳腺发育指标的定量分析；制作乳腺组织石蜡切片，利用免疫组织化学染色法检测增殖细胞相关抗原Ki67的表达。结果:对照组和低、高剂量砷暴露组仔鼠体重以及肝脏、肾脏和乳腺脏器系数比较，差异无统计学意义（ F=1.018、1.033、1.764、0.199， P均> 0.05）。与对照组比较，低、高剂量砷暴露组仔鼠有较多的导管终末乳芽（TEB）形成，乳腺导管的分支较多，纵向生长能力较强。定量分析结果显示，低、高剂量砷暴露组仔鼠的TEB数量（11.83 ± 4.40、11.00 ± 3.74）显著多于对照组（4.00 ± 1.83， P均< 0.05），乳腺导管长度[（6.43 ± 1.08）、（6.08 ± 1.74）mm]明显长于对照组[（3.71 ± 0.61）mm， P均< 0.05]，乳腺导管与淋巴结距离[（0.58 ± 1.12）、（- 0.02 ± 1.57）mm]明显小于对照组[（- 2.67 ± 0.87）mm， P均< 0.05]；低剂量砷暴露组仔鼠的平均最大TEB面积[（0.04 ± 0.01）mm 2]明显大于对照组[（0.02 ± 0.01）mm 2， P < 0.05]。低、高剂量砷暴露组仔鼠乳腺组织TEB内Ki67的染色强度与对照组相比显著增强。 结论:生命早期无机砷暴露促进了雌性小鼠TEB的发育、乳腺导管的延伸以及TEB内细胞的增殖，提示生命早期无机砷暴露能够影响乳腺发育。

abstractsObjective:To investigate the effects of drinking water-borne arsenic exposure on mammary gland development of female mice in early life.Methods:Healthy and sexually mature C57BL/6J mice were paired according to the female to male ratio of 2∶1. After confirmation of pregnancy, female mice were randomly divided into control (drinking double distilled water), low- (0.5 mg/L) and high- (5.0 mg/L) dose arsenic exposure groups, 10 mice in each group. The exposure time of arsenic in drinking water ranged from day 0 of pregnancy to day 28 after birth. At the end of arsenic exposure, female offspring (10 mice in each group) were sacrificed and mammary glands were dissected for whole tissue staining to evaluate the development of mammary glands and quantitative analysis of mammary gland development indexes. The expression of proliferating cell associated antigen Ki67 was detected by immunohistochemistry.Results:There were no significant differences in body weight and organ coefficients of liver, kidney and mammary glands between female offspring in low- and high-dose arsenic exposure groups and control group ( F=1.018, 1.033, 1.764, 0.199, P > 0.05). Compared with control group, low- and high- dose arsenic exposure groups showed more terminal end buds (TEB) and ductal branches as well as stronger longitudinal growth ability in mammary gland morphological analysis. Quantitative analysis results showed that the numbers of TEB in the low- and high-dose arsenic exposure groups (11.83 ± 4.40, 11.00 ± 3.74) were significantly higher than that in the control group (4.00 ± 1.83, P < 0.05). The ductal lengths in the low- and high-dose arsenic exposure groups [(6.43 ± 1.08), (6.08 ± 1.74) mm] were also significantly longer than that in the control group [(3.71 ± 0.61) mm, P < 0.05]. The distance of leading edge of ducts to the midpoint of lymph nodes in the low- and high-dose arsenic exposure groups [(0.58 ± 1.12), (- 0.02 ± 1.57) mm] was significantly shorter than that in the control group [(- 2.67 ± 0.87) mm, P < 0.05]. The mean maximum area of TEB in the low-dose arsenic exposure group [(0.04 ± 0.01) mm 2] was significantly larger than that in the control group [(0.02 ± 0.01) mm 2, P < 0.05]. Immunohistochemistry staining indicated strong staining of Ki67 within TEB in the low- and high-dose arsenic exposure groups. Conclusion:Early life inorganic arsenic exposure promotes the development of TEB, ductal extension and cell proliferation within TEB in female mice, indicating that early life arsenic exposure alters mammary gland development.