| Objective:To evaluate toxic effects of benzene on reproductive and embryonic development, The reproductive and embryonic developmenalt toxicity were assessed by exposing rats to the different levels of benzene.Methods:The SD rats (clean grade) including both male 36 and female 48, were randomly divided into four groups: placebo group, benzene vapor (BV) 5 mg/m~3 group, BV 10 mg/m~3 group and BV 15 mg/m~3 group. Firstly, the male rats continuous exposed to BV for 7 daily 2hr. Secondly, both male and female rats continuous exposed to BV for 7 daily 2hr when the males exposured to the first 28d. Thirdly, six rats from each group were sacrificed to examine for the different index at the 2d after all exposured to BV, which included not only the serum testosterone levels, the epididymal viscera coefficient, the testicular viscera coefficient and sperm abnormalities of males, but also the serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol levels (EL), ovarian corpus luteum (CL) and viscera coefficient of females. At the same time, the pathological observation on the testis had been also carried out. Finally, all the remaining female rats were co-caged overnight with the remaining male ones at 18:00 pm on the 2d after all exposured to BV, and the vaginal plugs of female rats and the mating rates were examined respectively at 8:00 on the next day. Afterwards, the fecundability and abortion rates of the female rats were observed during 5d, which the time we found the vagina! plugs was regarded as the "zero" day for the gestation. Next, the pregnant rats from each group were treated by BV again from the 6d to 15d. In addition, throughout the experiment period, not only all of the rat and the pregnant ones weights were investigated once weekly and every day respectively, but also the BV poisoning of rat were observed. After a short time (pregnant at 18d), the pregnant rats were sacrificed to investigate the growth and development status of embryos, fetal deaths, fetus resorptions, featus anomalies and placental weights.Results:1. The rats that exposed to BV had less action, less food intake, and bristling hair with poor gloss. There were no significant difference in growth rates for pregnant rats among 0 and 6d (P>0.05). After the pregnant rats from each group exposed to BV, their growth rates among 7 and 9d (pregnant 0-3d) showed no significant difference (P <0.05). However, growth rates of pregnant rats from BV 15 mg/m~3 group were lower than control group among 10 - 12d (P<0.05); in addition, growth rates from BV 10 mg/m~3 and BV 15 mg/m~3 group showed significant difference (P <0.05) bewteen 13 -15d and l6-18d.2. The male rat' epididymal and testicular weights from each group decreased with the increase of BV dose, but their epididymal and testicular viscera coefficient were lower than control group (P<0.05). Futhermore, The female rat'ovarian viscera coefficients from each group were lower than control group (P<0.05).3. Deformity rates of 1.90 %±0.14 %, 2.18 %±0.34 %, 2.83 %±0.26 %, 4.20 %±0.21 % had been obtained from the rats sperm of control, BV 5 mg/m~3, BV 10 mg/m~3 and BV 15 mg/m~3 group, respectively. Furthermore, deformity rates among the four group were statistically significant (F=182.35, P<0.01), which mainly include Big Head, Small head, banana head, hook-type head, double, three, neck bending, neck torsion, body bending, folding tail, short tail and so on.4. Histopathologic studies showed that the morphous and edges of the seminiferous tubule from control rat testes remained regular and intact. Moreover, in the inner wall of seminiferous, the tubule spermatogoniums, primary and secondary spermatocyte were densely clustered together from external to internal directions with clear hiberarchy, and a lot of mature sperm cells could also be seen in the lumen round the middle of seminiferous. However, the tubule from exposed rat testes differed from this pattern. Such as, irregular morphous, quite incomplete edges, different sizes, porous arrangement of cells in the inner wall, degeneration and even loss of spermatogoniums, primary and secondary spermatocyte. In brief, the higher the dose was, the more obvious the pathological damage was.5. The levels of testosterone in serum from exposed rat testes were lower than that from control ones (P<0.05). Though the levels of FSH,LH,E2 in serum from BV 5 mg/m~3 group were no significant difference from control ones (P>0.05), that from BV 10 mg/m~3 and BV 15 mg/m~3 group were lower than that from control ones (F<0.05).Likewise, the placental weights of rats from BV 10 mg/m~3 and BV 15 mg/m~3 group were lower than that from control ones(P<0.05).6. The occurrence probability of fetal deaths and fetus resorptions from BV 10 mg/m and BV 15 mg/m group could be added (P<0.05) though the pregnancy rates of rats from each group were no significant difference (P>0.05). The weights, body and tail length of the fetuses in the rats from BV 10 mg/m~3 and BV 15 mg/m~3 group were lower than that from control ones (P<0.05). Therefore, Benzene can inhibit the growth of fetal rats in vivo with a dose - response relationship.Conclusions:1. Benzene, responsible for reproductive toxicity of rat, can induce change in some index, such as hormone levels, sperm morphology, testis tissue of male rat, and hormone levels of female rat.2. Benzene, also responsible for embryonic development toxicity, can result in adverse pregnancy outcomes, growth and development delay of fetus and even death.
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