Abstract：
The present study aims to analyze the effects of developmental exposure to phthalates at environmentally relevant doses on the neural control of male and female reproduction. For this purpose, C57Bl/6J mice were exposed to di-(2-ethylexyl) phthalate (DEHP) alone (5 or 50 μg/kg/d), or DEHP (5 μg/kg/d) in a phthalate mixture. Exposure through diet started 6 weeks before the first mating and lasted until weaning of litters from the second gestation (multiparous dams). Analyses of offspring born from multiparous dams exposed to DEHP alone or in a phthalate mixture showed that females experienced a delayed pubertal onset, and as adults they had prolonged estrous cyclicity and reduced Kiss1 expression in the preoptic area and mediobasal hypothalamus. Male littermates showed a reduced anogenital distance and delayed pubertal onset compared with controls. However, in adulthood the weight of androgen-sensitive organs and hypothalamic Kiss1 expression were unaffected, suggesting normal functioning of the male gonadotropic axis. Developmental exposure to DEHP alone or in a phthalate mixture reduced the ability of intact males and ovariectomized and hormonally primed females to attract a sexual partner and to express copulatory behaviors. In addition, females were unable to discriminate between male and female stimuli in the olfactory preference test. Social interaction was also impaired in females, while locomotor activity and anxiety-like behavior in both sexes were unaffected by the treatment. The sexual deficiencies were associated with reduced expression of the androgen receptor in the preoptic area and progesterone receptor in the mediobasal hypothalamus, the key regions involved in male and female sexual behavior, respectively. Thus, the neural structures controlling reproduction are vulnerable to developmental exposure to phthalates at environmentally relevant doses in male and female mice. Adult females had an impaired gonadotropic axis and showed more affected behaviors than adult males.
摘要：
本研究旨在分析环境相关剂量的邻苯二甲酸酯的发育暴露对男性和女性生殖的神经控制的影响。为此,将C57Bl/6J小鼠单独暴露于邻苯二甲酸二（2-乙基己基）酯（DEHP）（5或50μg/kg/d），或邻苯二甲酸酯混合物中的DEHP（5μg/kg/d）。通过饮食暴露在第一次交配前6周开始，一直持续到第二次妊娠（多胎大坝）断奶。对单独暴露于DEHP或邻苯二甲酸酯混合物中的经产水坝出生的后代的分析表明，雌性经历了青春期的延迟，成年后，他们的发情周期延长，视前区和下丘脑中的Kiss1表达减少。与对照组相比，男性同窝显示出肛门生殖器距离减少和青春期发作延迟。然而,在成年期，雄激素敏感器官的重量和下丘脑Kiss1表达不受影响，表明男性促性腺激素轴的正常功能。单独或在邻苯二甲酸酯混合物中发育暴露于DEHP会降低完整的雄性，卵巢切除和激素灌注的雌性吸引性伴侣和表达交配行为的能力。此外,在嗅觉偏好测试中，女性无法区分男性和女性的刺激。女性的社交互动也受到了损害，而两性的运动活动和焦虑样行为均不受治疗的影响。性缺陷与视前区的雄激素受体和下丘脑中下丘脑的孕激素受体的表达减少有关，涉及男性和女性性行为的关键区域，分别。因此，在雄性和雌性小鼠中，控制生殖的神经结构容易受到环境相关剂量的邻苯二甲酸酯的发育暴露。成年女性的促性腺激素轴受损，受影响的行为比成年男性多。
