Subchronic Exposure to Di(2-ethylhexyl) Phthalate and Diisononyl Phthalate During Adulthood Has Immediate and Long-Term Reproductive Consequences in Female Mice
Subchronic Exposure to Di(2-ethylhexyl) Phthalate and Diisononyl Phthalate During Adulthood Has Immediate and Long-Term Reproductive Consequences in Female Mice
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DOI：
10.1093/toxsci/kfz013
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发表时间：
2019-04-01
影响因子：
3.8
通讯作者：
Flaws, Jodi A.
中科院分区：
文献类型：
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作者：
Chiang, Catheryne;Flaws, Jodi A.
邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种用于各种消费品的增塑剂。这是令人担忧的，因为DEHP是一种内分泌干扰物和卵巢毒物。邻苯二甲酸二异壬酯（DiNP）是一种DEHP替代品，由于其作为DEHP替代品的使用量增加，因此是一种正在上升的人类毒物。然而，关于成年期DEHP或DiNP暴露对女性生殖的影响知之甚少。因此，本研究检验了成年期DEHP或DiNP暴露对小鼠雌性生殖产生长期影响的假设。成年雌性CD-1小鼠（39-40天）经口给予溶剂对照（玉米油）、DEHP（20 μ g/kg/天-200 mg/kg/天）或DiNP（20 μ g/kg/天-200 mg/kg/天），持续10天。给药后即刻以及给药后3个月和9个月时，将雌性小鼠与未给药雄性小鼠配对进行繁殖试验。给药后即刻，DEHP和DiNP不会影响生育能力。给药后3个月，DiNP（20和100微克/公斤/天以及200毫克/公斤/天）显着扰乱了动情周期，DiNP和DEHP（20微克/公斤/天）显着降低了雌性怀孕的能力。在给药后9个月，DiNP显著破坏了发情周期（100 μ g/kg/天），减少了交配时间（100 μ g/kg/天-200 mg/kg/天），并临界降低了产生后代的雌性百分比（20 mg/kg/天）。在给药后9个月，DEHP（200 μ g/kg/天和200 mg/kg/天）和DiNP（100 μ g/kg/天和20和200 mg/kg/天）增加了雄性偏向窝仔的数量。这些数据表明，DEHP和DiNP暴露对女性生殖具有长期影响，即使在停止暴露后很长时间。
Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in a variety of consumer products. This is concerning because DEHP is an endocrine disruptor and ovarian toxicant. Diisononyl phthalate (DiNP) is a DEHP replacement that is a rising human toxicant due to its increased use as a DEHP substitute. However, little is known about the effects of DEHP or DiNP exposure during adulthood on female reproduction. Thus, this study tested the hypothesis that DEHP or DiNP exposure during adulthood has long-term consequences for female reproduction in mice. Adult female CD-1 mice (39-40 days) were orally dosed with vehicle control (corn oil), DEHP (20 mu g/kg/day-200 mg/kg/day), or DiNP (20 mu g/kg/day-200 mg/kg/day) for 10 days. Females were paired with untreated male mice for breeding trials immediately post-dosing and again at 3 and 9 months post-dosing. Immediately post-dosing, DEHP and DiNP did not affect fertility. At 3 months post-dosing, DiNP (20 and 100 mu g/kg/day and 200 mg/kg/day) significantly disrupted estrous cyclicity, and DiNP and DEHP (20 mu g/kg/day) significantly reduced the ability of females to get pregnant. At 9 months post-dosing, DiNP significantly disrupted estrous cyclicity (100 mu g/kg/day), reduced time to mating (100 mu g/kg/day-200 mg/kg/day), and borderline reduced percent of females who produced offspring (20 mg/kg/day). At 9 months post-dosing, DEHP (200 mu g/kg/day and 200 mg/kg/day) and DiNP (100 mu g/kg/day and 20 and 200 mg/kg/day) increased numbers of male-biased litters. These data show that DEHP and DiNP exposure has long-term consequences for female reproduction, even long after cessation of exposure.