Toxic Effects of Lactational Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on Development of Male Reproductive System: Involvement of Antioxidants, Oxidants, and p53 Protein

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent endocrine disruptor compound and induces multiple organ dysfunctions. The effect of TCDD exposure both in adults and in utero has been well established. However, little is known about the effects of TCDD acquired through mother's milk on the development of the male reproductive system. The aim of this study was to investigate the effects and mechanisms of TCDD from lactational exposure. TCDD (1 mu g/kg) was administered to C57BL/6 mouse mothers for 4 days from the day of delivery. On postnatal day 30 (PND 30) and postnatal day 60 (PND 60), body weight, body length, and anogenital distance (AGD) of male offspring were measured. The weights of the testes and epididymides were also measured. Epididymides were used for sperm counts, and testes were used to measure the activity of antioxidant enzymes (SOD, CAT, GPX, GR), the parameters of oxidative stress (hydrogen peroxide, MDA), and testosterone. In addition, expression of p53 and the proapoptotic protein, Bax, were analyzed by Western blot. TCDD exposure decreased body weight, body length, and AGD in both PND 30 and PND 60 groups compared with the control group. The activity of all antioxidant enzymes at PND 60 was decreased after TCDD treatment. TCDD treatment decreased testicular testosterone levels in both the PND 30 and PND 60 groups. The expression of p53 and Bax were also upregulated by TCDD and did not return to normal levels by PND 60. These data suggest that TCDD affects development of male offspring when the mother is exposed to TCDD during lactation. In addition, oxidative stress is a major mediator of TCDD-induced adverse effects, and p53 may play an important role in this mechanism. (C) 2008 Wiley Periodicals, Inc. Environ Toxicol 25: 1-8. 2010.