Effects Of Swainsonine-induced Glycosylation Mutation On Reproductive Hormone Secretion In Mice

Swainsonine is the main component of locoweed toxic alkaloids,when livestock feed locoweed lead after swainsonine poisoning,symptoms will stumble,weight loss and movement disorders.Swainsonine poisoning mainly due to the occurrence of extensive degeneration of animal tissue,it is due to inhibition of swainsonine glucosidase activity,causing N-glycan processing disorder,abnormal levels of glycosylation,mannose-rich the large accumulation of oligosaccharides in the cell,the disorder in many biological processes.Swainsonine effect on reproduction mainly: dams poisoning can cause infertility,reproductive hormone secretion disorder,ovarian tissue degeneration or apoptosis luteal cells;pregnant dams abortion occurs,the stillbirth,teratogenic,frail fetus,leading to reproductive performance.Glycosylation exists widely in all stages of the body,and gonadotropins belong to glycoprotein hormones.The level of glycosylation plays a decisive role in its normal activity and half-life.At the same time,gonadotropin receptors also have a glycosylated structure,and their function is restricted by the level of glycosylation.Reproductive hormones and their receptors are of decisive significance for the maintenance of normal pregnancy,and abnormalities of the two will inevitably cause reproductive disorders.So swainsonine how it affects the processing of N-glycans;how swainsonine affect the regulation of livestock reproductive hormone secretion;how swainsonine affect the secretion and expression of pregnant dams reproductive hormone receptors? Thus,this test was conducted by intraperitoneal injection of Swainsonine exposed mice to establish models poisoning,pregnancy record 6 d,11 d,16 d reproductive index mice,embryos pregnancy,embryo weight and the like.The survival rate and body weight of the pups were recorded at 0 d,7 d,and 14 d after delivery.The liver,spleen,ovary,placenta,and fetus(including the uterus)of mice at 6 days,11 days,and 16 days during pregnancy were collected for pathological observation.The blood and pituitary tissues of mice at 6 d,11 d,and 16 d during pregnancy were collected,and the glycosyltransferase activity,expression level,and monosaccharide level were measured by ELISA and Western Blot;the pituitary gland of the infected mice was selected,and the changes and changes of the sugar chain structure in the pituitary tissue were detected by MALDI-TOF-MS mass spectrometry.The blood and ovaries of mice at 6 d,11 d,and 16 d during pregnancy were collected,and the levels of reproductive hormones and their receptors and steroid rate-limiting enzyme proteins and genes were detected by ELISA,Western Blot,and quantitative PCR.Results of test one: The reproductive index,the number of pregnant embryos,the weight of embryos,the survival rate of the pups,and the weight of the mice in the swainsonine test group were decrease than normal group(P <0.05).Histopathological results in the experimental group: inflammatory reactions in the liver and spleen;hyperemia in early embryos,and hypoplasia in late embryos.Placental villous plate dysplasia;a large amount of glycan deposits in the lamina propria of endometrium;abnormal numbers of ovarian follicles and corpus luteum;Results of test two: Compared with the control group,the sugar chain structure of the pituitary gland in the test group changed,the number of composite glycosides gradually decreased,and the number of hybrid glycosides increased.The pituitary glycosyltransferase activity and protein expression of mice in the experimental group were decrease than normal group(P <0.05).The blood glucose level of mice in the test group was significantly lower than that in the control group(P <0.05);Results of test three: The activity of reproductive hormones was decrease than normal group(P <0.05).The expression levels of genes and proteins of reproductive hormone receptors in the experimental group were decrease than normal group(P <0.05).The expression levels of genes and proteins of sex steroid rate-limiting enzymes in the experimental group were decrease than normal group(P <0.05).Conclusion: Swainsonine inhibits the activity of key enzymes in N-glycan processing,causes abnormal synthesis of N-glycan,inhibits gonadotropin secretion,and further affects hormone activity by inhibiting reproductive hormone receptors.At the same time,bitter stigmatin causes disorder of sex steroid hormone secretion by inhibiting the rate-limiting enzymes of sex steroid hormone synthesis,eventually causing disorder of the body’s reproductive hormone secretion,and the reproductive performance of mice decreases.