Objective: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.