Effects Of Continuous Vitamin Deficiency From Early Life On Renal Function Of Offspring At Different Developmental Stages

Background and Objective: Chronic kidney disease(CKD)is a global public health problem.In some population studies,vitamin D(Vit D)and its active metabolite deficiency are common pathological features of CKD.The VDR receptor is abundant in the kidney and is the traditional target organ of Vit D.At the same time,Vit D deficiency is also an important public health problem worldwide.However,the effects of long-term vitamin D deficiency on kidney development and the mechanism of action are still unclear.The aim of this study was to investigate the effects of continuous vitamin deficiency from early life on renal function of offspring at different growth stages.On GD18,3 weeks(PD21),8 weeks(PD56),20 weeks(PD140),40 weeks(PD280)of different sex offspring mouse kidneys The effects of development and function,as well as the role of Vit D in mouse kidney development and function and related mechanisms.The purpose of this study was to investigate the effects of long-term Vit D deficiency on kidney development and function in different sex mice,and to explore the role of Vit D in mouse kidney development and function and related mechanisms.Methods: Four-week-old healthy and clean-grade ICR(CD-1)female mice were randomly divided into control group(Control)and Vit D-deficient diet-fed group(VDD),which were fed with standard feed and Vit D-deficient feed for 4 weeks respectively.Co-cage with male mice,the day of the vaginal plug was noted with GD0.On GD 18,part of the pregnant mice were sacrificed,the pregnant mice was retained,the sex of the fetus was discriminated and the weight and kidney weight were weighed.After three weeks of caged,according to the different maternal diet groups,the Vit D-deficient diet-fed group of rats continued to receive low Vit D feeding,and were randomly divided into female control group(Control)and female Vit D-deficient diet-fed diet group(VDD)and male control group.(Control)and male Vit D lack feed diet-fed group(VDD),3 weeks(PD21),8 weeks(PD56),20 weeks(PD140),40 weeks(PD280),and sacrificed on PD21,PD56,PD140,PD280,respectively,serum was taken,and the body weight and kidney were weighed.Serum levels of 25(OH)D and renal function were measured.Renal pathology,HE staining,pathological evaluation of renal pathology,renal tissue fibrosis using immunohistochemical staining and Sirius red staining,and we also analyzed the level of renal ?-SMA protein expression.Results: The results showed that serum 25(OH)D levels in the experimental group and PD140 mice were significantly lower than those in the control group.In PD280,serum 25(OH)D levels in male mice were significantly lower than those in the control group.PD140,Vit D deficiency diet feeding group,and the VDR signal of the kidneys of the offspring was significantly down-regulated.Therefore,an animal model of long-term vitamin D deficiency has been successfully established.Further studies have shown that the Vit D deficiency diet feeding group during pregnancy significantly reduced the birth weight(Bw)of the fetus.In PD21,PD56,the weight and kidney weight of male rats in the control group were significantly higher than those in the VDD group,and there was no significant difference in renal coefficient.In PD140,PD280,VDD group,the weight of male mice was significantly higher than that of the control group,and the kidney weight was lower than that of the control group,but the kidney coefficient was significantly higher than that of the control group(P<0.05).In PD21,the weight and kidney weight of the female mice in the control group were significantly higher than those in the VDD group.In the remaining stages,there was no significant difference in body weight,kidney weight and kidney coefficient between the control group and the experimental group.Pathological analysis showed that in PD140,the kidney structure of male mice in VDD group changed slightly,and the kidney structure of female mice in VDD group did not change.At the same time,there was no statistical difference in renal function between control group and experimental group.In PD280,the kidney structure of VDD group of male mice was significantly changed compared with the control group,serum creatinine and uric acid were significantly higher than the control group(P<0.05)and the expression level of VDR in the experimental group was significantly down-regulated,and the fibrosis area,?-SMA protein positive area and expression level were significantly up-regulated.Conclusion: Continuous vitamin deficiency from early life leads to a decrease in birth weight of fetal mice,and causes kidney atrophy in elderly male mice,and pathological changes and renal function damage in the area of renal fibrosis.However,it has less effect on the kidney of female mice.