Exposure of Adult Female Mice to Low Doses of di(2-ethylhexyl) Phthalate Alone or in an Environmental Phthalate Mixture: Evaluation of Reproductive Behavior and Underlying Neural Mechanisms.
Exposure of Adult Female Mice to Low Doses of di(2-ethylhexyl) Phthalate Alone or in an Environmental Phthalate Mixture: Evaluation of Reproductive Behavior and Underlying Neural Mechanisms.
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DOI：
10.1289/ehp7662
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发表时间：
2021-01
影响因子：
10.4
通讯作者：
Mhaouty-Kodja S
中科院分区：
文献类型：
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作者：
Adam N;Brusamonti L;Mhaouty-Kodja S
我们以前已经表明，成年雄性小鼠暴露于低剂量的普遍存在的内分泌干扰物，邻苯二甲酸二（2-乙基己基）酯（DEHP），改变求偶行为。在雌性小鼠中分析了成年小鼠单独暴露于低剂量DEHP或环境邻苯二甲酸酯混合物对发情周期、生殖行为和潜在神经结构的影响。两个月大的C57 BL/6 J雌性动物经口暴露于单独的DEHP（0、5或）或邻苯二甲酸酯混合物中的DEHP（）6周。在完整小鼠中分析了发情周期，并在雌二醇和孕酮引发的卵巢切除小鼠中测量了行为[脊柱前凸，嗅觉偏好，伴侣偏好，刺激雄性超声发声（USV）的能力]。用免疫组织化学方法对雌激素受体（ER）和孕激素受体（PR）在大鼠行为神经结构中的表达进行了研究。单独或混合暴露于DEHP延长了发情周期持续时间，发情前期较短，发情期和发情后期较长。在正常的激素水平下，单独或混合接触DEHP的女性表现出嗅觉偏好的改变。观察到较低的脊柱前凸行为和吸引和刺激求偶USVs的雄性排放的能力，可能是由于暴露的雌性中的信息素排放的修改。行为改变与PR表达神经元数量减少有关，而性行为背后的神经回路没有变化。两种DEHP剂量之间观察到的大多数效应相当，并且由混合物中的DEHP驱动。暴露于环境剂量的DEHP单独或混合物改变了小鼠雌性性行为的几个组成部分，可能是通过选择性破坏神经PR信号。与先前报道的雄性小鼠的脆弱性一起，这一发现表明邻苯二甲酸酯暴露对有性生殖的重大影响，包括具有类似神经调节过程的其他物种。https://doi.org/10.1289/EHP7662
We have previously shown that adult male mice exposure to low doses of an ubiquitous endocrine disruptor, di(2-ethylhexyl) phthalate (DEHP), alters courtship behavior. The effects of adult exposure to low doses of DEHP alone or in an environmental phthalate mixture on estrous cyclicity, reproductive behavior, and underlying neural structures were analyzed in female mice. Two-month-old C57BL/6J females were exposed orally for 6 wk to DEHP alone (0, 5 or ) or to DEHP () in a phthalate mixture. Estrous cyclicity was analyzed in intact mice, and behavior [lordosis, olfactory preference, partner preference, ability to stimulate male ultrasonic vocalizations (USVs)] was measured in ovariectomized mice primed with estradiol and progesterone. Immunohistochemical studies were conducted in the neural structures involved in behavior for estrogen receptor (ER) and progesterone receptor (PR). Exposure to DEHP alone or in mixture lengthened the estrous cycle duration, with a shorter proestrus and longer estrus and metestrus stages. Under normalized hormonal levels, females exposed to DEHP alone or in mixture exhibited altered olfactory preference. A lower lordosis behavior and ability to attract and stimulate male emission of courtship USVs was observed, probably due to modifications of pheromonal emission in exposed females. The behavioral alterations were associated with a lower number of PR-expressing neurons, without changes in , in the neural circuitry underlying sexual behavior. The majority of effects observed was comparable between the two DEHP doses and were driven by DEHP in the mixture. Exposure to environmental doses of DEHP alone or in mixture altered several components of female sexual behavior in mice, probably through selective disruption of neural PR signaling. Together with the previously reported vulnerability of male mice, this finding suggests a major impact of exposure to phthalates on sexual reproduction, including in other species with similar neural regulatory processes. https://doi.org/10.1289/EHP7662