The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada H3G 1A4.
Toxicol Appl Pharmacol. 2013 Jan 1;266(1):95-100. doi: 10.1016/j.taap.2012.10.027. Epub 2012 Nov 8.
Di-(2-ethylhexyl) phthalate (DEHP) is used industrially to add flexibility to polyvinyl chloride (PVC) polymers and is ubiquitously found in the environment, with evidence of prenatal, perinatal and early infant exposure in humans. In utero exposure to DEHP decreases circulating testosterone levels in the adult rat. In addition, DEHP reduces the expression of the angiotensin II receptors in the adrenal gland, resulting in decreased circulating aldosterone levels. The latter may have important effects on water and electrolyte balance as well as systemic arterial blood pressure. Therefore, we determined the effects of in utero exposure to DEHP on systemic arterial blood pressure in the young (2month-old) and older (6.5month-old) adult rats. Sprague-Dawley pregnant dams were exposed from gestational day 14 until birth to 300mg DEHP/kg/day. Blood pressure, heart rate, and activity data were collected using an intra-aortal transmitter in the male offspring at postnatal day (PND) 60 and PND200. A low (0.01%) and high-salt (8%) diet was used to challenge the animals at PND200. In utero exposure to DEHP resulted in reduced activity at PND60. At PND200, systolic and diastolic systemic arterial pressures as well as activity were reduced in response to DEHP exposure. This is the first evidence showing that in utero exposure to DEHP has cardiovascular and behavioral effects in the adult male offspring.
邻苯二甲酸二(2-乙基己基)酯(DEHP)在工业上用于增加聚氯乙烯(PVC)聚合物的柔韧性,并且在环境中普遍存在,人类在产前、围产期和婴儿早期都有接触 DEHP 的证据。在子宫内暴露于 DEHP 会降低成年大鼠循环中的睾丸激素水平。此外,DEHP 会降低肾上腺中的血管紧张素 II 受体的表达,导致循环中的醛固酮水平降低。后者可能对水和电解质平衡以及全身动脉血压有重要影响。因此,我们确定了子宫内暴露于 DEHP 对年轻(2 个月大)和老年(6.5 个月大)成年大鼠的全身动脉血压的影响。妊娠的 Sprague-Dawley 母鼠从妊娠第 14 天到出生时每天接受 300mg DEHP/kg 的暴露。在出生后第 60 天(PND60)和第 200 天(PND200),通过主动脉内传送器收集雄性后代的血压、心率和活动数据。在 PND200 时,使用低(0.01%)盐和高盐(8%)饮食来挑战动物。子宫内暴露于 DEHP 导致 PND60 时的活动减少。在 PND200 时,暴露于 DEHP 会导致收缩压和舒张压以及活动降低。这是首次表明子宫内暴露于 DEHP 会对成年雄性后代的心血管和行为产生影响的证据。