| Over a long period of time, the health risk assessment of chemical pollutants was based on their oncogenic potentials. In the past decades, scientists acknowledged that the effect of toxic chemicals could produce profound harmful outcome to reproduction and development of human being and animals. And this may be one of the reasons related to sterility, miscarriage, malformation and malfunction of newborn animals. This reproductive index is more sensitive than others for screening toxic chemicals. Extensive studies had been conducted in this area since then and the assessment of chemicals on the reproduction and development has been routinely used in drug and pollutants analysis and evaluation process in west countries. China experienced a high rate of economic growth in past decades, in which inevitably with a rapid growth of using numeric of new chemicals and increasing of waste drainage. Establishment of relevant assessment system is a prerequisite for guaranteeing the newly introduced material shall not jeopardize our public health. Utilizing an EPA scientists recommended Early Pregnancy Protocol, use NIH mouse as test animal, a TCDD toxicity model for early pregnant mouse was made for establishing an early pregnancy toxicity screening system. TCDD was initially chosen in this study since it represents a group of very toxic chemicals existed in wide range of environment. Another reason is that although the reproductive toxic effects of TCDD is most intensively investigated, the effects on early pregnancy (before implantation) has not been examined in spite of evident showing that this is the most sensitive stage.Three parts of studies are reported in this thesis:Part one: Early Pregnancy Protocol. In this part a series of experiments are Included: 1. Dose-response evaluation. Groups of pregnant NIH mice were dosed orally with 0, 2.0, 50 and 100 ng·kg-1·d-1 of TCDD on days 1-8 of early pregnancy. The animals were sacrificed on day 9,the numbers of embryo implantation sites, the weight of embryo were recorded. 2. Pre- versus Post- implantation Analysis. The pregnant animals were dosed with same amount of TCDD but on days 1-3 and 4-8 of early pregnancy respectively, the numbers of embryo implantation sites, the weight of embryo were recorded. 3. Decidua cell response. Groups of pseudo-pregnant NIH mice were dosed orally with same amount of TCDD on Days 1-8,1-3 and 4-8 of early pregnancy. The animals were sacrificed on day 9,and the weights of the uterus of pseudo-pregnant mice were recorded. 4.Embryo Transport Rate Analysis. The pregnant animals were dosed with same amount of TCDD but on days 1-3, animals were sacrificed on day 1,day 2,and day 3 to check the position of embryo.The results showed that the number of implantation sites decreased significantly(P＜0.05) with the occurrence of post-implant embryo death and retardation of embryo development when the mice were dosed with 50 and 100 ng·kg-1·d-1 TCDD; And this treatment inhibited uterus deciduas growth of pseudo-pregnant mice significantly (P＜0.01). Pre- versus Post-implantation analysis revealed that pre-implantation stage is more sensitive than post-implantation stage. The embryo transport rate was not changed in TCDD treated animals. But the embryo in the oviduct was observed to be un-synchronization in development with a proportion of embryo loss. A groups of TCDD treated animals was allowed to had the fetus until d18. The survival rate was compared with d9 data. The result showed that the d18 survival rate is significantly lower than d9, TCDD caused development retardation and death of post-implantation embryos. Part two: Mechanism of TCDD toxicity on early pregnant mouse: 1.Reproductive hormones. Progesterone and estrogen are the dominant hormone in embryo implantation process and sustaining the post-implanted embryo development and growth. Changes of cycling hormones in pregnant mouse may be key important in interpreting the harmful effects of TCDD. The serum of experiment animals in the PPP were collected when the mouse was...
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