| The mammalian ovary is a heterogeneous organ contains follicles at different developmental stages.Ovulation and steroid hormones synthesis are the main functions of ovary.After sexual maturation,under the influence of the hypothalamicpituitary-ovarian axis,the primordial follicles are periodically activated and developed to complete the process of ovulation.Changes in the internal and external environment can affect the homeostasis of ovarian microenvironment,causing abnormal development of oocytes and follicles,which subcutaneously leads to ovulation disorders and female infertility.Heavy metals generally have a long half-life and difficult to be degraded and are prone to bioaccumulation after entering the environment.Cadmium(Cd)is a kind of heavy metal that coexists with zinc in nature.It is often discharged into the environment as a by-product during zinc smelting,causing water and soil pollution.Due to its special physical and chemical properties,cadmium is often used in nuclear reactor control,alloy manufacturing,electroplating and rechargeable batteries.Taking in the contaminated water or food through digestive tract,inhaling the cadmiumcontaining dust and smoke(such as cigarette smoke),touching the cadmiumcontaining products are the main route of cadmium exposure.After entering the human body,cadmium is mainly metabolized in the liver and kidney,and reaches the various organs including the ovary through the blood it is difficult to be metabolized.It often reaches the organs including the ovary through the blood circulation,but the low clearance rate will ultimately result in the accumulation of cadmium in human body.There are few studies on the effects of cadmium on female reproductive system,and there is no unified conclusion on the underlying mechanisms.Melatonin(Mel),which chemical structure is N-acetyl-5-methoxytryptamine,is a hormone secreted mainly by vertebrate pineal gland.Peripheral tissues such as retina,gut,ovary,and placenta can also produce this indoleamine.Its main function is to regulate the biological rhythm.Melatonin also modulates oxidative stress,endoplasmic reticulum stress,inflammation and apoptosis in different disorders,which can attenuate various organic disorders.However,there is no relevant study on the protective effect of melatonin on the cadmium-exposed ovaries.PurposeThe aim of this study was to investigate the underlying mechanism of Cd-induced ovary dysfunction,and the possible protective effect of melatonin,which suggests the potential clinical application of melatonin in the protection of ovarian function.Method1.Cadmium chloride was injected intraperitoneally to construct a mouse model of cadmium exposure,and the morphology and structure of the ovary were observed.2.Some cadmium-exposed mice were treated with melatonin at the same time to observe the morphology of the ovaries.The ovulation function of each group was observed after ovulation induction treatment;3.Evaluated the ER stress in the ovaries through the Western Blotting and RT-qPCR.4.Evaluate the level of apoptosis in the ovaries through the Western Blotting and Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL)assay Results1.Exposure to cadmium chloride resulted in the loss of body weight,irregular of estrous cycle,disruption of ovarian structure and dysfunction of ovulation, the apoptosis level was also increased in the Cd-treated mice;2.The addition of melatonin attenuated the pressure in endoplasmic reticulum,ameliorated the cell apoptosis in ovarian tissues,the number of ovulated oocytes was increased significantly compared with the mice that treated with cadmium chloride alone.Conclusion1.The application of melatonin can improve the abnormality of ovarian tissue and ovulation disorders in mice caused by cadmium chloride;2.The underlying mechanisms may associate with the effects of melatonin alleviating the increase of endoplasmic reticulum pressure in ovarian tissue caused by cadmium chloride,thereby improving ovarian tissue apoptosis. |
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