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Effects Of Levonorgestrel And Quinestrol On The Expression Of CYP1A2 Of Brandt’s Voles

Posted on:2017-04-11Degree:MasterType:Thesis
Country:ChinaCandidate:Z H JiFull Text:PDF
GTID:2283330485986612Subject:Cell biology
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Rodents damage the grain crops, grassland and spread disease, the fertility control technology is one of the most effective pest control technology. Levonorgestrel is a kind of synthetic progesterone; Quinestrol is a kind of synthetic estrogen. It has proved that they can make different degrees of reproductive suppression effect on a variety of rodents.The contraceptive can not only make animals sterile but also be toxic, high dose will cause rodents poisoning death. Therefore, accurate estimation of sterile toxicity is particularly important. CYP1A2 is a cytochrome P450 (cytochrome P450) molecular, responsible for activation of some drugs, the substances before becoming toxic and carcinogenic in vivo, oral contraceptives can inhibit the activation of CYP1A2. Brandt’s voles (Lasiopodomys brandtii) mainly distributed in Lake Baikal of Russia, Northern and Eastern of Mongolian, Heilongjiang, Jilin, Liaoning, Hebei et al. It can destroy grassland vegetation, graze the crop, and spread disease, resulting in serious rodent damage.In this study, Brandt voles, as the research object, are taken L-Q(1:1) and its composition by gavage.Through identificating changes of multiplication and reproductive systems by paraffin, measuring hormones related to reproductive by ELISA, identificating CYP1A2 mRNA expression level by quantitative PCR test, we want to select a P450 molecular which can indicate the toxicity of the three components. The main research in this paper is as follows:1) Effects of the contraceptive on the multiplication of the Brandt voles; 2) Effects of the contraceptive on the reproductive structure system of the Brandt voles; 3) Effects of the contraceptive on the regulation of the reproductive hormones; 4) Effects of the contraceptive on the expression of CYP1A2.Based on the research, the results are as follows:1) Q significantly reduced the body weight of the Brandt voles, while L did not. The most significant reduction was at 14d after lavage. L, Q, and L-Q all played a role in inhibiting the reproduction of the mice, the rate of pregnancy was almost 0, only group L had a fetal, and the gestation period was prolonged, the number of litter reduced, the fetus was not formed, the uterus was red and swollen. While in the control group, the pregnancy rate was 85.7%, the average litter size was 4.86±0.53, significantly higher than that of the drug group.2) The contraceptive had obvious effect on the uterus of the female, but had no significant effect on the ovary, Q can significantly reduced the uterine weight, while group L was not significant. In the treatment group, the morphology of the uterus was thin, and easy to break, but the regularity was not strong. The contraceptive had obvious effect on testis and epididymis, Q can significantly reduce the weight of testis and epididymis, while group L and L-Q were not significant. Sections showed that the seminiferous tubules decreased significantly in the male testis and epididymis, Lumen became empty, the number of sperm cells decreased, apoptosis, and Q group was the most significant than L group and L-Q group.3) The two contraceptive had obvious effects on FSH, but had no significant effect on estradiol, testosterone and corticosterone. Compared with the control group, the FSH of L-Q group was lower; L and Q had no great changes. Two factor variance concluded L was the main function factors, Q is not significant, and there is no interaction between the two. That is to say L can significantly inhibit the expression of follicle stimulating hormone, Q and L on the expression of estradiol, testosterone, and corticosterone did not work.4) The contraceptive has a significant impact on CYP1A2, Q can significantly inhibit the expression of CYP1A2, while L can not, but the two have significant interaction. Group Q had a serious liver injury, it’s appearance look like erosion and water filling, there are a lot of necrotic areas, the color became dark, surface became rough. The liver slice showed the enlarged liver cells, tissue edema, hepatic cell staining shallow, accompanied by bleeding condition, decreasing liver density, increasing lacuna. The results of the other two groups were not significant.The conclusions of this study are as follows:1) Q at a dose of 2 mg/kg could inhibit the body weight of Brandt’s voles; both L and Q could reduce the rate of pregnancy and litter size, they all played a role that made Brandt’s voles infertility.2) Q was a male sterile agent, inhibiting the formation of sperm in testis and the maturation of sperm in the epididymis. L was a female sterile agents, inhibiting the secretion of FSH.3) Q was more toxic, it showed the inhibition to the mRNA expression of CYP1A2 and significant liver damage.
Keywords/Search Tags:Brandt’s voles, Levonorgestrel, Quinestrol, Multiplication, Reproductive system, Gender hormone, CYP1A2
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