Exposure to DEHP decreased four fatty acid levels in plasma of prepartum mice.
Exposure to DEHP decreased four fatty acid levels in plasma of prepartum mice.
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DOI：
10.1016/j.tox.2013.04.010
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发表时间：
2013-07-05
期刊：
影响因子：
4.5
通讯作者：
Nakajima T
中科院分区：
文献类型：
--
作者：
Nakashima R;Hayashi Y;Md K;Jia X;Wang D;Naito H;Ito Y;Kamijima M;Gonzalez FJ;Nakajima T
母体暴露于邻苯二甲酸二（2-乙基己基）酯（DEHP）可降低糖尿病小鼠的血浆甘油三酯。为了鉴定所涉及的脂肪酸（FA）种类并了解潜在机制，用含0%、0.01%、0.05%或0.1% DEHP的饲料处理妊娠Sv/129野生型（mPPARα）、过氧化物酶体增殖物激活受体α-null（Pparα-null）和人源化PPARα（hPPARα）小鼠。在妊娠第18天与胎仔一起解剖母鼠，并在出生后第2天与新生儿一起解剖母鼠。测量母体血浆和野生型后代肝脏中的n-3/n-6多不饱和、饱和和单不饱和FA，以及母体肝脏中FA去饱和和延长的代表性酶。妊娠对照mPPARa小鼠的血浆亚油酸、α-亚麻酸、棕榈酸和油酸水平高于Ppara-null和hPPARα小鼠。DEHP暴露仅显著降低妊娠mPPARα小鼠中这四种FA的水平。妊娠小鼠血浆中多种脂肪酸的水平高于产后小鼠，且与基因型无关，而胎儿肝脏中脂肪酸的水平低于幼鼠。DEHP暴露轻微增加了胎仔的肝脏花生四烯酸、α-亚麻酸、棕榈油酸和油酸，但在幼崽中没有。然而，DEHP暴露并未明显影响所有母鼠肝脏中FA去饱和酶1和2以及延伸酶2和5的表达。总之，妊娠mPPARα小鼠血浆中碳链较短的四种FA水平高于其他基因型小鼠，DEHP暴露仅降低了mPPARα小鼠的这些特定FA浓度，与甘油三酯水平相似。
Maternal exposure to di(2-ethylhexyl) phthalate (DEHP) decreased the plasma triglyceride in prepartum mice. To identify the fatty acid (FA) species involved and to understand the underlying mechanisms, pregnant Sv/129 wild-type (mPPARα), peroxisome proliferator-activated receptor α-null (Pparα-null) and humanized PPARα (hPPARα) mice were treated with diets containing 0%, 0.01%, 0.05% or 0.1% DEHP. Dams were dissected on gestational day 18 together with fetuses, and on postnatal day 2 together with newborns. n-3/n-6 polyunsaturated, saturated, and monounsaturated FAs in maternal plasma and in liver of wild-type offspring, and representative enzymes for FA desaturation and elongation in maternal liver, were measured. The plasma levels of linoleic acid, α-linolenic acid, palmitic acid and oleic acid were higher in the pregnant control mPPARa mice than in Ppara-null and hPPARα mice. DEHP exposure significantly decreased the levels of these four FAs only in pregnant mPPARα mice. Plasma levels of many FAs were higher in pregnant mice than in postpartum ones in a genotype-independent manner, while it was lower in the livers of fetuses than pups. DEHP exposure slightly increased hepatic arachidonic acid, α-linolenic acid, palmitoleic acid and oleic acid in fetuses, but not in pups. However, DEHP exposure did not clearly influence FA desaturase 1 and 2 nor elongase 2 and 5 expressions in the liver of all maternal mice. Taken together, the levels of plasma four FAs with shorter carbon chains were higher in pregnant mPPARα mice than in other genotypes, and DEHP exposure decreased these specific FA concentrations only in mPPARα mice, similarly to triglyceride levels.
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