| Polycystic ovary syndrome(PCOS)is an endocrine disease caused by many factors.It not only affects women’s fertility and metabolism,but also causes endometrial thickening and increases the risk of cancer.The pathogenesis of PCOS was not clear,the main viewpoints were: the effect of hyperandrogen on the hypothalamus pituitary ovary axis;exposed to environmental toxins;genetic factors and susceptible gene variation.Animal models for PCOS research included rodents,sheep and rhesus monkeys,which is a non-human primates,at present.Rhesus monkey was a suitable animal model to study PCOS disease,because its genes,menstrual cycle,reproductive characteristics and other aspects were closest to human beings,and there were also natural PCOS characteristics.However,because of its high price and long birth cycle,it was not feasible to use them for animal model of PCOS.Because of the rodents small size and short reproductive cycle,they have been the most widely used animal model of PCOS at present.Since no naturally occurring rodent PCOS animal model had been found,the most commonly methods were to inhibit the construction with androgen or aromatase.It is necessary to build a natural,genetic,high success rate and stable animal model.When our research group used borderline hypertensive rat(BHR)to establish the animal model of preeclampsia,we had a discovery.We found that the reproductive capacity of the female BHR decreased,some female BHR even losed the reproductive capacity.Further study found that there were polycystic ovaries(PCO)like changes in the female BHR with infertile,but there were no mature follicles in the ovary.BHR was the offspring of female Spontaneously hypertensive rat(SHR)with male Wistar Kyoto(WKY).BHR has the genetic gene of maternal spontaneous hypertension.We propose a hypothesis that the female BHR with PCO was a naturally occurring PCOS rodent models.If the hypothesis was true,the female BHR will become the appropriate model for the study of PCOS genetic phenotype.The BHR pups were separated from their nursing mother rats on the 21 st day after birth,especially the female pups were selected for feeding.The female BHRs were weighed from 21 days of birth,once a week until the end of the experiment.From 11 weeks of age after birth,the female BHR were made vaginal smears every day until the end of the experiment to identify its estrous cycle.At the age of 12 weeks after the birth of BHR,the ovaries,uterus,adipose tissue and blood samples were collected during the estrus interval.The indexes to be observed include weight and weight growth,Body mass index(BMI),clitoris length,distance from vagina to anus,estrus cycle,weight of ovary and uterus,length of uterus,morphological change of ovary and uterus,changes in the size of peritoneal adipocytes,the size of gonad,and serum sex hormone levels.A total of 46 female BHR were divided into two groups: 25 in normal group(54.3%)and 21 in PCO group(45.7%).The grouping was based on the results of pathological of BHR ovaries.In the normal group,body length was 18.5(18.3,18.7)cm,body weight was 164.0(158.4,167.1)g,BMI was(4.9±0.3)kg/m2,clitoral length was 0.5(0.5,0.6)cm,vaginal opening distance from anus was 1.2(1.0,1.2)cm,ovarian weight was 104.8(100.0,110.0)mg.In the PCO group,body length was 19.3(19.0,19.9)cm,body weight was 190.7(184.4,196.8)g,BMI was(5.1±0.3)kg/m2,clitoral length was 0.7(0.7,0.8)cm,vaginal opening distance from anus was 1.4(1.3,1.5)cm,ovarian weight was 130.3(126.4,139.0)mg.Compared with the above indexes,female rats in the PCO group were increased(P<0.01).In the normal group,uterine length was 3.5(3.4,3.5)cm,the difference in uterine length between the left and right sides was 0.5(0.4,0.5)cm.In the PCO group,uterine length was 3.0(2.9,3.3)cm,the difference in uterine length between the left and right sides was 0.1(0.0,0.2)cm,were lower than that in normal group(P<0.001).There were no difference in cervical length and uterine weight between the two groups(P>0.05).The weight gain of the PCO group were higher than that of normal group between 21-84 days after birth(P<0.05).Female BHR in the normal group had regular estrus cycle,with an average of 4～5 days.Female BHR in the PCO group,the oestrus cycle was not regular,the diestrus interval was prolonged or remained in the diestrus interval.The serum testosterone(T)level of the normal group was(1.4 ± 0.8)ng/m L,and that of PCO group was(3.2 ± 0.4)ng/m L.The serum T level of the PCO group was 2 times higher than that of normal group(P<0.01).The serum estrone(E),luteinizing Hormone(LH)and LH/FSH(follicle Stimulating Hormone)of the normal group were as follows: 39.3(26.4,42.9)pg/m L,235.6(135.0,268.8)pg/m L,33.9±3.4.The serum E,LH and LH/FSH of the PCO group were as follows: 48.3(40.0,56.2)pg/m L,283.1(237.0,361.5)pg/m L,52.9±3.8.The levels of T,E,LH and LH/FSH of the PCO group were higher than those in the normal group(P<0.05).In the normal group,normal follicles were found in ovaries,while in PCO group,multiple and enlarged follicles and atretic follicles were found.The epithelial layer of endometrium of the PCO group was thicker than that of the normal group.In the PCO group,the columnar cells were abnormal in shape and arranged irregularly,and there were no cilia on the surface of endometrial layer.The adipocytes of peritoneum and gonad of the PCO group were larger than that in the normal group.The above results showed that the changes of the BHR with PCO in estrus cycle,pathological index,sex hormone biochemical index and body apparent index were consistent with the characteristics of PCOS animal model.The female BHR with PCO could be used as an animal model of PCOS to study etiology and molecular mechanism. |
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