Detection Of Changes In Sox9 Expression And The Effect On Pancrease Development Induced By Intrauterine Growth Restriction

Aims: To investigate the changes in pancreatic structure and Sox9 expression in intrauterine growth retardation(IUGR)and the effect on the development of pancrease cells.Methods: Selecting eighty virgin female Wistar rats weighing 250–300 g and 15 healthy male Wistar rats weighing 300–320 g.Wistar rats(1:4 [male:female])were mated overnight.Pregnant rats were randomly fed a standard or low-protein diet and their offspring were labeled as the control(CON)or IUGR group,respectively.The offspring of rats on days 15.5、18.5 gestation and the newborn weights were recorded and pancreases were collected.The body weights below the mean values of the body weights of the control group by > 2SD were regarded as IUGR rats.Histopathologic and ultrastructural changes were noted by HE staining and transmission electron microscopy,respectively.The expression of m RNA was detected by RT-PCR,protein expression was determined by Western blot 、 immunohistochemical staining,and immunofluorescence double staining.Results:(1)The pancreatic acinar and duct structure gradually formed the typical endocrine and exocrine structures.The ultrastructure of the pancreas showed that the mitochondria and the zymogen granules became larger.The expression of Sox9 protein was mainly expressed in the pancreatic duct during the development period and the level of expression was significantly decreased gradually(P <0.01).The co-expression of Sox9 and Pdx1 protein decreased gradually.(2)Embryonic(E15.5-E18.5)and newborn rats(P1)weighing < 0.222 g,1.251 g,and 5.17 g,respectively,were considered to be IUGR.The offspring of mother rats that were fed a low-protein diets had lower birth weights compared with the offspring of mothers who ate a normal diet.The incidence of IUGR groups was 40%、53%、and 84%,respectively.Compared with the CON group,the number of pancreatic acinar、duct,and islet structure were lower in the IUGR group.The expression of Sox9 and Pdx1 m RNA was decreased(P<0.05).The expression of Sox9 protein in the pancreatic duct was decreased(P< 0.05).The co-expression of Sox9 and Pdx1 was decreased.Conclusion: Sox9 was highly expressed in the developmental stage,which indicated that Sox9 mainly regulates the development of pancreatic progenitor cells.IUGR can cause the decreased expression of Sox9 in pancreatic progenitor cells,which affects the development of pancreatic endocrine cells and leads to pancreas structural damage.