Furukawa Satoshi, Hayashi Seigo, Usuda Koji, Abe Masayoshi, Hagio Soichiro, Ogawa Izumi
Biological Research Laboratories, Nissan Chemical Industries, Ltd., 1470 Shiraoka, Minamisaitama, Saitama 349-0294, Japan.
J Toxicol Pathol. 2011 Jun;24(2):95-111. doi: 10.1293/tox.24.95. Epub 2011 Jun 30.
The placenta grows rapidly for a short period with high blood flow during pregnancy and has multifaceted functions, such as its barrier function, nutritional transport, drug metabolizing activity and endocrine action. Consequently, the placenta is a highly susceptible target organ for drug- or chemical-induced adverse effects, and many placenta-toxic agents have been reported. However, histopathological examination of the placenta is not generally performed, and the placental toxicity index is only the placental weight change in rat reproductive toxicity studies. The placental cells originate from the trophectoderm of the embryo and the endometrium of the dam, proliferate and differentiate into a variety of tissues with interaction each other according to the development sequence, resulting in formation of a placenta. Therefore, drug- or chemical-induced placental lesions show various histopathological features depending on the toxicants and the exposure period, and the pathogenesis of placental toxicity is complicated. Placental weight assessment appears not to be enough to evaluate placental toxicity, and reproductive toxicity studies should pay more attention to histopathological evaluation of placental tissue. The detailed histopathological approaches to investigation of the pathogenesis of placental toxicity are considered to provide an important tool for understanding the mechanism of teratogenicity and developmental toxicity with embryo lethality, and could benefit reproductive toxicity studies.
胎盘在孕期短时间内迅速生长，血流丰富，具有多种功能，如屏障功能、营养转运、药物代谢活性及内分泌作用。因此，胎盘是药物或化学物质诱导的不良反应的高度敏感靶器官，已有许多胎盘毒性药物被报道。然而，胎盘的组织病理学检查一般并不进行，在大鼠生殖毒性研究中，胎盘毒性指标仅为胎盘重量变化。胎盘细胞起源于胚胎的滋养外胚层和母体的子宫内膜，按照发育顺序相互作用，增殖并分化为多种组织，从而形成胎盘。因此，药物或化学物质诱导的胎盘病变根据毒物和暴露时间的不同表现出各种组织病理学特征，胎盘毒性的发病机制较为复杂。胎盘重量评估似乎不足以评估胎盘毒性，生殖毒性研究应更加关注胎盘组织的组织病理学评估。详细的组织病理学方法用于研究胎盘毒性的发病机制，被认为是理解致畸性和胚胎致死性发育毒性机制的重要工具，并且可能有益于生殖毒性研究。
