| Objective: To determine the content of sex hormones and the protein expression of TGF-?1 in Hypothalamic-pituitary-ovarian on model of fluorosis,and to explore its mechanism.Methods:120 female rats were divided into 4 groups: control group(common feed),low fluoride group(content of fluorosis:25mg/Kg),middle fluoride group(content of fluorosis:50mg/Kg),high fluoride group(content of fluorosis:100mg/Kg);30 rats in each group were treated with sodium fluoride.The rats were fed continuously for 5 months;Ten female rats of each group were sacrificed at 3months,4 months and 5 months respectively during the estrus cycle;weighing and fixing the organization of hypothalamus-pituitary-ovary.Serum and left femur were collected.Tissues were sampled when the rats were terminated and the urine of the rats was collected.Observing the occurrence of dental fluorosis.HE was used to observe the pathological changes of hypothalamus-pituitary-ovary.Sex hormones were measured by the method of RIA.Timmunohistochemical method was used to detect the expression of TGF-beta 1 in the hypothalamus-pituitary-ovary of female rats.Results:1.Establishment of fluorosis animal model: The growth state of the rats in the experimental group decreased with the exposure time,and the weight increased more slowly than the control group(P<0.05).No obvious dental fluorosis occurred in the control group.Different degrees of dental fluorosis occurred in the other groups and the degree of dental fluorosis in the other groups was increased with the increase of the dose(P<0.05).The results showed that the bone fluoride in the fluoride group were higher than those in the control group(P <0.05).The degree of bone fluoride and urine Fluoride in the other groups was increased with the increase of the dose and exposure time.The combination of dental fluorosis and urinary fluoride and bone fluoride were considered to be successful in this study.2.Effects of fluoride onhypothalamus-pituitary-ovary in female rats: There was no significant difference in the organ coefficients of hypothalamus and pituitary in female rats in each exposure group(P>0.05);HE staining showed slight edema but no other significant pathological changes in the hypothalamus and pituitary;the tissue morphology,corpus luteum,the number of primordial follicles and primary / secondary follicles decreased significantly and the number of atresia follicles increased in ovarian.The Ovarian organ coefficient was higher the control group with long-term exposure(P<0.05).3.Effects of fluoride on the hypothalamus-pituitary-ovarian gonadal hormone in female rats: The levels of GnRH and LH in the serum of female rats in the middle fluoride group and the high fluoride group were higher than those in the control group and the low fluoride group.The levels of FSH in the serum of female rats in each exposure group was statistically significant in the 150 days(P <0.05).And the levels of of GnRH,FSH and LH in serum increased with the exposure time(P <0.05).the levels of E2,INH,P in serum in different groups decreased gradually with the increase of exposure dose and prolongation of exposure time,while the levels of T increased gradually(P <0.05).4.Effects of fluoride on the expression of TGF-?1in Hypothalamic-pituitary-ovarian in female rats:The expression of TGF-?1 in the hypothalamus of each exposure group was statistically significant only 150 days(P<0.05),which was increased in the hypothalamus with exposure dose and decreased first and then increased with the prolongation of exposure time.The expression of TGF-?1 in the pituitary of female rats was statistically significant in 120 days and 150days(P<0.05).which was decreased in the pituitary with exposure dose and time.The expression of TGF-?1 in ovarian in the 90 days,120 days and 150 days was statistically significant(P<0.05),and which was affected to decrease by the dose of exposure and exposure time.Conclusion:1.Fluorosis can lead to changes of the ovarian in hypothalamus-pituitary-ovarian.2.Fluorosis can lead to the increasing of GnRH ? FSH ? LH ? T and the decreasing of INH ? P ? E2 in hypothalamus-pituitary-ovarian in female rats.3.Fluorosis can lead to the increasing expression of TGF-?1 in Hypothalamus and the decreasing expression of TGF-?1 in pituitary and ovary in female rats,and which mainly influence the changes ofreproductive endocrine hormones by mediating TGF-?1expression in the ovary. |
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