Estrogenic action by tris(2,6-dimethylphenyl) phosphate impairs the development of female reproductive functions
Estrogenic action by tris(2,6-dimethylphenyl) phosphate impairs the development of female reproductive functions
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三(2,6-二甲基苯基)磷酸酯的雌激素作用会损害女性生殖功能的发育
DOI：
10.1016/j.envint.2020.105662
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发表时间：
2020
影响因子：
11.8
通讯作者：
Maekawa Fumihiko
中科院分区：
文献类型：
--
作者：
Sano Kazuhiro;Matsukami Hidenori;Suzuki Go;Htike Nang Thinn Thinn;Morishita Masahiro;Win-Shwe Tin-Tin;Hashimoto Shunji;Kawashima Takaharu;Isobe Tomohiko;Nakayama Shoji F.;Tsukahara Shinji;Maekawa Fumihiko
在发育过程中暴露于具有雌激素样活性的环境化学品被怀疑会永久损害妇女的健康。在这项研究中，小鼠模型被用来评估是否三（2，6-二甲基苯基）磷酸盐（TDMPP），一种化学与推定的雌激素样作用，损害大脑的性别分化。从妊娠第14天（GD）至分娩，对母鼠皮下给予TDMPP和17β-雌二醇（E2）作为阳性对照或芝麻油作为阴性对照，并从出生后第0天至第9天（PND）对幼仔皮下给予TDMPP和17β-雌二醇（E2）作为阴性对照。在TDMPP和E2治疗组中发现了性早熟、不规则的发情周期和降低的脊柱前凸反应。围产期脑内有一定量的TDMPP及其代谢产物，治疗后雌性小鼠下丘脑性二型核团雄性化。实验证据表明，TDMPP直接进入胎儿和新生儿脑，从而引起与性别相关的脑结构的变化，损害女性生殖功能。
Developmental exposure to environmental chemicals with estrogen-like activity is suspected to permanently impair women’s health. In this study, a mouse model was used to evaluate whether tris(2,6-dimethylphenyl) phosphate (TDMPP), a chemical with a putative estrogen-like action, impairs sexual differentiation of the brain. Either TDMPP and 17β-estradiol (E2) as positive controls or sesame oil as a negative control were administered subcutaneously to dams from gestational day (GD) 14 to parturition, and to pups from postnatal day (PND) 0 to 9. Precocious puberty, irregular estrous cycles, and a lowered lordosis response were found in the TDMPP- and E2-treated groups. A certain amount of TDMPP and its metabolites in the perinatal brain and the masculinization of sexual dimorphic nuclei in the hypothalamus of female mice after treatment were also detected. The experimental evidence demonstrates that TDMPP directly enters the fetal and neonatal brain, thereby inducing changes of sex-related brain structures and impairing female reproductive functions.