Manservisi Fabiana, Gopalakrishnan Kalpana, Tibaldi Eva, Hysi Albana, Iezzi Manuela, Lambertini Luca, Teitelbaum Susan, Chen Jia, Belpoggi Fiorella
Cesare Maltoni Cancer Research Center, Ramazzini Institute, Bologna, Italy(1).
Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, NY, United States.
Reprod Toxicol. 2015 Jul;54:110-9. doi: 10.1016/j.reprotox.2014.12.013. Epub 2014 Dec 29.
The aim of the study is to determine whether low doses of "endocrine disrupting chemicals" (EDCs) affect the development and proliferative activity of the mammary glands (MGs). Adult parous/nulliparous female Sprague-Dawley (SD) rats were treated from post-natal day (PND) 1 until PND 180 with diethylphthalate (DEP), methylparaben (MPB), triclosan (TCS) and a mixture at doses comparable to human exposure. The doses (mg/kg b.w./day) were: DEP=0.173; MPB=0.105; TCS=0.05. EDC treatment resulted in mortality rates >20% in pups as early as lactation day 7. Significant morphological/histological changes were observed at the end of lactation in the MGs of EDC-treated dams. The total transcriptome profile as well as lactation-related genes in MGs also corroborate the morphological findings as more profound gene expression changes are present only at the weaning period. The study highlights the heightened sensitivity of the MGs during critical windows of exposure, particularly pregnancy and lactation, with an impact on pups' survival.
本研究的目的是确定低剂量的“内分泌干扰化学物质”(EDCs)是否会影响乳腺(MGs)的发育和增殖活性。将成年经产/未产雌性斯普拉格-道利(SD)大鼠从出生后第1天(PND 1)至第180天用邻苯二甲酸二乙酯(DEP)、对羟基苯甲酸甲酯(MPB)、三氯生(TCS)以及与人暴露剂量相当的混合物进行处理。剂量(mg/kg体重/天)分别为:DEP = 0.173;MPB = 0.105;TCS = 0.05。EDC处理导致幼崽早在哺乳期第7天的死亡率>20%。在哺乳期结束时,观察到经EDC处理的母鼠的乳腺出现了显著的形态学/组织学变化。乳腺的总转录组图谱以及与泌乳相关的基因也证实了形态学发现,因为只有在断奶期才出现更深刻的基因表达变化。该研究强调了乳腺在关键暴露窗口期,特别是妊娠和哺乳期的高度敏感性,这对幼崽的存活有影响。