The Mechanism Study Of Premature Ovarian Failure

ObjectivePremature ovarian failure refers to development of amenorrhoea due to cessation of ovarian function before the age of 40 years. The diagnosis is based on elevated FSH levels and low E2 levels. In these years , nearly 2-fold age-specefic increase in mortality rate has been reported, omen with POF often present with infertility and sex steroid deficiency, then this disease is an important reason to effect women's health implications. So many studies had done to assess the incidence and medical intervention of POF.The incidence of POF is not well established,and has not appropriate medical intervention for this.In early studies, the known causes include:①genetic aberrations, the overall incidence of family with POF case to be 10%.②autoimmune ovarian damage, as suggested by the observed, association of POF with other autoimmune disorders, such as autoimmune thyroiditis, addison's disease, rheumatoid arthritis , systemic lupus erythematosus(SLE), diabetes and etc. .③cigarette smoking often cause women experience menopause earlier. Women with depression have also been reported to have an increased risk for developing POF.④environmental factors like virus infections , toxins and surgery on ovarian are all associated with POF.Ovarian tissue in human is difficult to acquie, so animal model is an ideal way to access the incidence , diagnosis and interventions of POF.4-vinylcyclohexene diepoxide (VCD) , metabolite of VCH(4-vinylcyclohexene) ,which is produced during the manufacture of rubber tires, flame retardants, insecticides, plasticizers, and antioxidants. It is difficult to avoid exposuring to these toxicants in woman worked in the related factory.Overseas experiments indicate that dosing with VCD causes gradual ovarian failure in rat. As a result, the animal undergoes ovarian failure, but retains residual ovarian tissue. It is not found in domestic literature.The animal experiment and a retrospective study on clinical patients are made in this article to access the effects of industrial chemicals and surgery on ovarian function in order to establish a suitable animal model and study further the incidence, diagnosis and intervention of POF.Methods1. Female SD rats(35-days) were taken, intraperitoneal injection three chemicals identically, such as VCD, sesame oil and physiological saline were emploided , then observe the variety of estrous cycle in these three groups.2. Acquiring rat's peripheral blood in these three groups after intraperitoneal injection 20-days, 40-days, 60-days, to test the diversity of hormone levels(FSH,LH,E2,P).3. Acquiring rat's ovarian and uterus after intraperitoneal injection VCD 20-days, 40-days, 60-days to make section, then observe the diversity of histology in rat 's ovarian and uterus, and count the quantity of apoptosis cells and ovarian follicles.4. Observing the expression of caspase3 in rat's ovarian after intraperitoneal injection VCD 20-days, 40-days, 60-days by immunity staining.5. A retrospective study on 67 women with ovarian endometriomas (previously diagnosed by open or laparoscopic surgery) receiving COH for IVF—ET regarding their outcomes of assisted reproduction was made to access the effect of surgery on ovarian.Result1. At 60th-day After intraperitoneal injection VCD, estrous cycle is disorder in 75% rats, and the volume of ovarian and uterus in 60-days group are all atrophied compared with the control group. 2. At 60th-day After intraperitoneal injection VCD, the level of FSH in rat's peripheral blood were significantly higher than in the control group(P<0.05).3. The number of primordial follicle and growing follicle in rat's ovarian with VCD injection were significantly fewer than in the control group (p<0.01).4. Caspase3 was expressed in nucleus of oocyte and granulose cell, sometimes it was expressed in both cytoplasm and nucleus. The number of Caspase3-stain cells and apoptosis index(AI) of resting follicles in VCD experimental groups were all increased than the corresponding control group (p<0.01).5. The level of FSH in the serum of surgery group is higher than that of no- surgery group(p<0.05), but the quantity of antral follicles and the volume of ovarian are significant fewer than in control group (p<0.05).Conclusion1. VCD could induce Premature Ovarian Failure in rat , and this can be an appropriate animal model to study the incidence of POF.2. VCD may activated apoptosis by caspase3 to induce POF in rat.3. Both laparoscopic and open cystectomy of ovarian endometriomas may cause damage to ovarian function.