School of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea; Department of Life Science, Chung-Ang University, Seoul 156-756, Republic of Korea.
School of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
Environ Toxicol Pharmacol. 2014 Nov;38(3):845-51. doi: 10.1016/j.etap.2014.10.008. Epub 2014 Oct 22.
Simazine is a suspected endocrine disruptor and the second most commonly detected pesticide in surface and groundwater worldwide. We evaluated the toxicity of simazine in female mouse offspring with in utero and lactational exposure to the agent. Pregnant mice were exposed to environmentally relevant doses (from 5 to 500μg/kg) of simazine via oral administration, and their female offspring were then analyzed. The female offspring showed shortened anogenital distance and decreased whole body, ovarian, and uterine weights. Their ovaries showed increased apoptotic granulosa cells. In addition, expression of critical genes involved in regulation of cellular apoptosis and proliferation was significantly downregulated in the ovaries of simazine-exposed mice. Moreover, in vitro exposure of human granulosa cell-derived KGN cells to simazine (0.003-1nM) resulted in decreased viability and proliferation. Thus, the present study demonstrates that maternal exposure to low doses of simazine impairs normal development of female offspring via disturbance of cellular apoptosis and proliferation.
西玛津是一种疑似内分泌干扰物，也是世界范围内地表水和地下水中检测到的第二大农药。我们评估了西玛津对经母体宫内和哺乳期暴露于该物质的雌性小鼠后代的毒性。通过口服给予怀孕小鼠环境相关剂量（5 至 500μg/kg）的西玛津，并对其雌性后代进行分析。雌性后代的肛门生殖器距离缩短，全身、卵巢和子宫重量减轻。它们的卵巢中出现凋亡的颗粒细胞增多。此外，西玛津暴露组小鼠卵巢中与细胞凋亡和增殖调控相关的关键基因表达明显下调。此外，西玛津（0.003-1nM）对人卵巢颗粒细胞衍生的 KGN 细胞的体外暴露导致细胞活力和增殖降低。因此，本研究表明，母体暴露于低剂量的西玛津通过干扰细胞凋亡和增殖而损害雌性后代的正常发育。
