The Effect Of Methoxychlor On Endometrial Morphology And It's Regulation On The Expression Of ERα,IGF-1 In Mouse

Endometrial paraplasm and endometrial cancer are the most frequent diseases in female reproductive system,and their morbidity rates are constantly increasing,which threaten female healthy seriously. It is well known that the progression from normal endometrium to endometrial adenocarcinoma is through under the control of inheritance,estrogen,progesterone,growth factors,oncogenes,et al.Many studys discover that environmental endocrine-disrupting chemicals (EDCs) may mimic,or modulate the synthesis,release,transport,metabolism and binding or elimination of natural estrogen. They may cause harmful effects on fertility and fecundability,birth defects,metabolic disorder,reproductive system cancer,especially whose potential hazardous effects on endometrial diseases have been noted.The potential hazardous effects of estrogen-like chemicals may cause endometrial cancer. EDCs include persistent pollutants,agrochemicals and widespread industrial compounds.Methoxychlor (MXC) is an insecticide developed to replace dichlorodiphenyltrichloroethane. Investigations find the residue of MXC located not only in soil,river,but also in body of human and wildlife,particularly in blood serum,lipid-rich tissues,liver. We have found that MXC have estrogenic effects in rat,which make uterine quality increase.EDCs have been shown to mimic estregon by interacting with estrogen receptor(ER)and eliciting responses generally attributed to estregon,leading to concern for their potentials to disrupt the female reproductive systems. It is generally accepted that estrogens exerts its effects in target organs by binding to ER and modulating the expression of various proteins such as growth factors. In the uterus,one such growth factor is IGFs. The IGF system consists of two ligands,IGF-1 and IGF-2;two cell-membrane receptors,IGF-1 receptor (IGF-1R) and IGF-2 receptor (IGF-2R);and six high-affinity IGF binding proteins,IGFBP-1 through-6. The IGF pathway components are thought to regulate cell proliferation and differentiation in autocrine and paracrine manner. The effects of IGF-1 on cell proliferation are mediated by the activation of the IGF-1R. Many epidemiologic studies investigate various kind of factors stimulate IGF-1 gene expression in the uterus and has been shown to induce endometrial proliferation in mouse uterine epithelial cells. Evidences has been mounting that the overexpression of IGF-1 may be linked to a high rate of endometrial cancer.The purpose of this study is to investigate the effect of MXC on endometrial morphology the expression of ERα,IGF-1 in mouse. The main research findings of our research are as follows:1. 7-week old mature female mice were randomly divided into 4 groups and treated with corn oil,MXC of 50,100,200mg/kg,respectively. After the treatment for 30d , the endometrial thickness , the size of gland and glandularlumen were measured from routine histological slides using computerized image analysis. The SP immunohistochemical techniques was employed to semiquantitative analysis the ERα. Compared with control,there are significantly difference in the endometrial thickness,the size of gland and glandularlumen,the total area of glandular cells,the average height of glandular epithelium in the other groups (P<0.05). Moreover,The expression of ERαin the groups of 100 , 200mg/kg were significantly increased than control group(P<0.05) .2. IGF-1 expression in mouse uterus was tested with immunochemistry method and semiquantitative analysis. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of mRNA isoforms of IGF-1 in mouse uterus. Compared with control,The positive rate of IGF-1 protein in the groups of 100 , 200mg/kg were significantly increased respectively(P<0.05). Moreover,The expression of IGF-1 mRNA in the groups of 100,200mg/kg were higher than that of the controls(P<0.05) .In our research,we found that with long-term exposure (intraperitoneal injection) to MXC,intense changes were found in the mouses,including an increase in the endometrial thickness,the size of gland,glandularlumen,the total area of glandular cells,the average height of glandular epithelium and ERα(P<0.05). The expression of IGF-1 in mouse endometrium was up regulated(P<0.05). IGF-1 mRNA expression level was closely related to endometrium hyperplasia with exposure to MXC. It is indicated that the overexpression of ERα,IGF-1 may play a crucial role in the origin and development.