Chen Jiangang, Laughlin Lisa S, Hendrickx Andrew G, Natarajan Kala, Overstreet James W, Lasley Bill L
Center for Health and the Environment, University of California at Davis, One Shields Avenue, Davis, CA 95616-8739, USA.
Toxicology. 2003 Apr 15;186(1-2):21-31. doi: 10.1016/s0300-483x(02)00601-7.
As many as 62% of all human conceptions are lost prior to 12 weeks of pregnancy and it is unknown how many of these losses result from environmental hazards. Previous studies have shown that single doses of 1, 2, and 4 microg/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) administrated orally to cynomolgus macaques during the peri-implantation period leads to early fetal loss (EFL) within 10-20 days. TCDD induced EFL is associated with a reduction in the biological activity of monkey chorionic gonadotrophin (mCG) but no change in the immunoreactive mCG profile. These studies are consistent with either a direct effect of TCDD on differentiation of the trophoblast and an indirect effect on mCG synthesis, or a direct effect on mCG synthesis and secretion independent of trophoblast development. The present study was designed to test the hypothesis that the action of TCDD is directly on mCG synthesis rather than on the differentiation of the trophoblast. Female macaques (Macaca fascicularis) were treated with a single dose of TCDD (4 microg/kg b.wt.) on Gestational Day 20, a stage of pregnancy following initial trophoblast differentiation and invasion. Circulating mCG concentrations were monitored for the next 6 days. Compared to the controls, the peak level of serum bioactive mCG was lower in the treated group (P<0.05), with a decrease observed on the day following exposure. The bioactive/immunoreactive mCG ratio was also lower in the treated group compared to the controls (P<0.05). There was no difference in serum immunoreactive mCG levels between the groups. Histological evaluation of the embryo-placental unit showed increased apoptosis and vascular congestion after treatment but was otherwise grossly normal. Because exposure of the conceptus to TCDD following differentiation of the trophoblast decreased the bioactivity of circulating mCG, we conclude that the action of TCDD in the placenta is directly on mCG synthesis.
多达62%的人类受孕在怀孕12周前就已失败，目前尚不清楚这些失败中有多少是由环境危害导致的。先前的研究表明，在植入期前后给食蟹猴口服单剂量的1、2和4微克/千克2,3,7,8-四氯二苯并对二恶英（TCDD）会导致在10 - 20天内出现早期胎儿丢失（EFL）。TCDD诱导的EFL与猴绒毛膜促性腺激素（mCG）的生物活性降低有关，但免疫反应性mCG谱没有变化。这些研究结果与TCDD对滋养层分化的直接作用以及对mCG合成的间接作用一致，或者与对mCG合成和分泌的直接作用（独立于滋养层发育）一致。本研究旨在检验TCDD的作用直接作用于mCG合成而非滋养层分化这一假设。在妊娠第20天（即初始滋养层分化和侵入后的妊娠阶段）给雌性食蟹猴（食蟹猕猴）单剂量注射TCDD（4微克/千克体重）。在接下来的6天里监测循环中的mCG浓度。与对照组相比，治疗组血清生物活性mCG的峰值水平较低（P<0.05），在接触后的第二天就观察到了下降。治疗组的生物活性/免疫反应性mCG比值也低于对照组（P<0.05）。两组之间血清免疫反应性mCG水平没有差异。对胚胎 - 胎盘单位的组织学评估显示，治疗后细胞凋亡增加和血管充血，但在其他方面大体正常。由于在滋养层分化后使孕体接触TCDD会降低循环中mCG的生物活性，我们得出结论，TCDD在胎盘中的作用直接作用于mCG合成。
