Establishment Of A Rat Model Of Congenital Abnormalities Of The Kidney And The Urinary Tract In Offspring Due To Gestational Diabetes Mellitus

Objective:To explore the feasibility of establishing a rat model of Congenital abnormalities of the kidney and the urinary tract(CAKUT)due to Gestational diabetes mellitus(GDM)by a single intraperitoneal injection of different doses of streptozotocin(STZ).Methods:36 female SD rats and 18 male rats were mated naturally,30 pregnant rats were selected in the order of pregnancy and injected with STZ intraperitoneally on day 1.5 of gestation(E 1.5),and the pregnant rats were divided into 5 groups according to the different dose of STZ:STZ 30mg/kg group,STZ 35 mg/kg group,STZ 40 mg/kg group,solvent control group(injected with the same dose of sodium citrate buffer),and blank control group(not injected with any liquid),each group n=6.the weight and blood glucose of pregnant rats were monitored during pregnancy.On the first day of delivery,the abortion rate of females and the live birth rate of offspring were calculated,and the offspring were dissected to observe the abnormalities of the urinary tract;Hematoxylin-eosin staining of cross sections of offspring rats was performed,renal and ureteral abnormalities were observed and recorded in multiple sections,and the renal cortical thickness of sub-rats was measured.Results:(1)Ureteral effusion was observed in the three groups of STZ 30,35 and 40 mg/kg,in which the total incidence of ureteral dilated effusion was higher than that of the blank control group(P<0.05),reaching more than 70%,and there was no difference in the composition ratio of ureteral effusion between the three groups(P>0.05),The incidence of bilateral ureteral dilatation and effusion in all three groups was more than three times that of unilateral,and microscopic observation(HE staining)showed dilatation and effusion of the ureter and dysplasia of the ureteral wall.(2)Renal dysplasia of the offspring rats was observed microscopically(HE staining)in all three groups of STZ 30,35 and 40 mg/kg,which showed thinning of renal parenchyma and lower renal cortical thickness than that of the blank control group(P<0.05),with a reduction of more than 20%,but there was no difference in renal cortical thickness between the three groups(P>0.05).(3)The blood glucose values of STZ 30,35 and 40 mg/kg groups were higher than those of the blank control group(P<0.05),and all of them reached the modeling standard of 16.7 mmol/L.The mean blood glucose values in the STZ 30 mg/kg group were lower than those in the STZ 40 mg/kg group(P<0.05),and there was no difference between the mean blood glucose values in the STZ 30 mg/kg group and the STZ 35 mg/kg group(P>0.05),and the blood glucose in the STZ 35 mg/kg group was lower than that in the STZ 40 mg/kg group in early pregnancy(P<0.05),and there was no statistical difference in the middle and late pregnancy(P>0.05).(4)The abortion rate of pregnant rats in the STZ 40 mg/kg group was 33.33%,while the abortion rate of the remaining groups was 0.There was no difference in the live birth rate among the three groups of STZ 30,35 and 40 mg/kg(P>0.05),and the live birth rate of all three groups was lower than that of the blank control group(P<0.05),and the weight of the rats in all three groups was lower than that of the blank control group(P<0.05).Conclusions:It is feasible to establish the CAKUT model of GDM rat offspring with a one-time intraperitoneal injection of STZ,and bilateral or unilateral ureteral effusion and renal dysplasia can be observed in the offspring.The modeling scheme of a one-time intraperitoneal injection of STZ 30 mg/kg on gestation day 1.5(E 1.5)in SD rats can produce stable urological malformations in the offspring,as well as ensure safer blood glucose during pregnancy and a lower miscarriage rate,and can be the preferred modeling protocol.