Effect Of Quercetin On Rat Reproductive Development And Genistein And Quercetin On Mice Ovary And Serum Hormone And Blood Fat

Premature ovarian failure(POF)is the loss of function of the ovaries before age 40 for the patients who have a normal menarche or delayed adolescent age and normal female secondary sexual characteristics.It,due to a multitude of undetermined causes,is a syndrome in young women characterized by persistent amenorrhea and genital atrophy.The patients have menopausal levels of follicle stimulating hormone(FSH)and luteinizing hormone(LH),but low estrogen levels.In contrast with natural menopause,POF sufferers demonstrate ovarian follicle depletion or destruction and loss of eggs or infertility resulted in ovarian failure.In recent years,the academic researchers pay close attention to the effect of phytoestrogen in the occurrence and development of estrogen-related tumors.Population epidemiological datas and animal studies demonstrated that low-dose of diethylstilbestrol(DES)exposure could lead to a variety of diseases of the female reproductive system including uterine leiomyoma.Moreover,low-dose of DES in the early development of exposure was considered more directly related to the occurrence of uterine leiomyoma.So many animal experiment results support the hypothesis that at equal effect similar to DES,exposure to envronmental endocrine disruptors during early development periods can result in uterine leiomyoma which are not manifested until later in life.Among many recognized phytoestrogens,genistein(Gen)and quercetin(Que),a representative of the flavonoid,are present in human diet and have estrogen-like effects.The effect of Gen and Que on pregnant women,infants,and post-menopausal women should get more and more attention in recent years.They may bring about women's health hazards,especially in menopausal breast cancer and uterine leiomyoma.So it is very important to clarify dietary phytoestrogens exposure for the women of premature ovarian failure in the occurrence and development of estrogen-related tumors.Therefore,the specific aim of our study,establishing the autoimmune premature ovarian failure as a model by using Zona pellucida3(ZP3),is to investigate the mechanism of tumor development,consequently to provide theoretical guidance for phytoestrogens risk assessment.The main contents of this study are as follows:1.The effect of quercetin exposure during perinatal period on female rat reproduction and growth of their offspringIn this study,we applied a perinatal rat model to investigate reproductive changes of female rat that exposed to different doses of quercetin in the gestation and lactation and the development and growth of their offspring.The mother rats and their offspring were examined for growth indices,reproductive capacity,and pup survival and anogenital distance(AGD)at regular time intervals during the administration period.The results showed that there is no difference between quercetin group and control group on maternal body weight,reproductive capacity and pup survival.The AGD and body weight of male pups,whose mother rats exposed to low-and middle-dose quercetin,were significantly decreased but the AGD and body weight of female pups have no difference comparing to the control group.Thus it can be seen that quercetin has estrogen and anti-estrogen effect,greater impacts in male pups,but no reproductive and developmental toxicity.2.The effect of quercetin exposure for zona pellucida-induced autoimmune premature ovarian failure mouse model on ovary and levels of serum hormones and blood lipidIn this study,we established animal model of autoimmune POF by hypodermic injection of ZP3 in both hind footpads of BALB/c mice,and the model mices were exposed to different doses of quercetin which aims to investigate the effect of Que on ovarian morphology and levels of serum hormones and blood lipid.The results showed that the mices at low-dose(5 mg/kg)of Que could be significantly reduced body weight and increased AGD which may lead to female pseudohermaphroditism.And in this group the autoimmune oophoritis(AOS)is more serious than middle-and high-doses of Que.On the contrary,for the mices who exposed to middle-dose of Que(25 mg/kg),the body weight was greatly increased and AGD was decreased comparing to control group.Moreover,in the blood lipid,the levels of total cholesterol,total triglyceride,low-density lipoprotein cholesterol were greatly reduced and the level of high density lipoprotein cholesterol was increased comparing to model group;in the ovarian morphology,the proportions of growing follicles and mature follicles were increased,the proportions of atretic follicle and primordial follicles were decreased,and the incidence of AOS was reduced.3.The effect of genistein exposure for zona pellucida-induced autoimmune premature ovarian failure mouse model on ovary and levels of serum hormones and blood lipidIn this study,we established animal model of autoimmune POF by hypodermic injection of ZP3 in both hind footpads of BALB/c mice,and the model mices were exposed to different doses of genistein which aims to investigate the effect of Gen on ovarian morphology and levels of serum hormones and blood lipid.The results showed that the mices at low-dose(5 mg/kg)of Gen could be significantly reduced body weight and increased AGD which may lead to female pseudohermaphroditism.And in this group the autoimmune oophoritis(AOS)is more serious than middle-and high-doses of Gen.On the contrary,for the mices who exposed to high-dose of Gen(45 mg/kg),the body weight was greatly increased and AGD was decreased comparing to control group.Moreover,in the blood lipid,the levels of total cholesterol,total triglyceride,low-density lipoprotein cholesterol were greatly reduced and the level of high density lipoprotein cholesterol was increased comparing to model group;in the ovarian morphology,the proportions of growing follicles and mature follicles were increased,the proportions of atretic follicle and primordial follicles were decreased,and the incidence of AOS was reduced.All above,these studies not only provided a new therapeutic strategy for the patients with premature ovarian failure,but also provided theoretical guidance for the safety of a diet rich in phytoestrogens.This has a great significance for the application and market value of phytoestrogens in the future.