The Influence Of Intrauterine Chronic Hypoxia On The Renal Structure And Tissue RAS In Adult Mouse Offspring

Objectives The aim of the study was to investigate the influence of intrauterine chronic hypoxia on the renal structure and tissue RAS in adult mouse offspring,and to explore the possible mechanism of chronic intrauterine hypoxia on the renal structural abnormalities of adult offspring.It aimed to provide experimental and theoretical basis for the prevention of related “the fetal Origins of adult diseases”,so as to improve the level of perinatal health care and prenatal and postnatal care for pregnant women.Methods 1.When the C57BL/6 mice were mated,twenty pregnant mcie were randomly assigned to the normal control group(group A)and the intrauterine chronic hypoxia group(group B),each group contained ten C57BL/6 pregnant mice.Group B was placed in the hypoxic chamber,where the oxygen concentration was controlled at(10±1)%.Group A was placed in a hypoxic chamber of the same specification but the air was continuously supplied.The rest conditions were the same as those of group B.After maintaining the state for 3 hours per day,the mice were removed and placed in the air.This process was repeated until delivery,and a model of C57BL/6 pregnant mice intrauterine chronic hypoxia was established.2.After pregnancy,pregnant mice were randomly kept with 3 male pups per litter(30 in group B and 30 in group A,60 in total),then weighed and recorded.3.The offspring mice were kept under the same conditions until 3 months old and 6 months old.Eight mice were randomly selected from each group and weighed.Retained urine to detect urine protein,taking blood after anesthesia to detect serum creatinine and blood urea.After the mice were killed by cervical dislocation,both kidneys were quickly obtained,one side(left side)kidney tissue was made into a wax block to make a pathological section.Then,the whole kidney tissue was observed by HE staining,the glomerular morphology was observed by PAS staining,the renal interstitial was observed by Masson staining.The renal local renin RAS components of the other side(right side)which contained angiotensin ACE,ACE2,Agtr1,Mas R,were detected by Q-PCR and Western Blot;then renal Ang II and Ang-(1-7)concentration were detected by ELISA.Results 1.When compared with the normal control group,the birth weight of the offspring mice that came from the intrauterine chronic hypoxia group significantly decreased,but there were no significant differences in body and kidney weight as well as the ratio of kidneyto-body weight between the normal control group and the intrauterine chronic hypoxia group for both 3-month-old offspring mice and 6-month-old offspring mice.2.When compared with the normal control group,there were no significant differences in the urine protein as well as the serum creatinine and blood urea between the normal control group and the intrauterine chronic hypoxia group for both 3-month-old offspring mice and 6-month-old offspring mice.3.For 3 –month-old offspring mice,the renal structure of the intrauterine chronic hypoxia group showed a few of certain changes.HE staining,PAS staining,and Masson staining were used to observe glomerulosclerosis and dilatation of the renal tubule,further studies showed that the intrauterine chronic hypoxia group had significantly higher Ang?and Ang(1-7)concentrations in kidney tissue,the expression of ACE m RNA and protein in kidney tissue also significantly increased,but the expression of ACE2 m RNA and protein in kidney tissue significantly decreased,when compared with the normal control group.4.For 6 –month-old offspring mice,the renal structure of the intrauterine chronic hypoxia group showed a few of certain changes,HE staining,PAS staining,and Masson staining were used to observe glomerulosclerosis and dilatation of the renal tubule,HE staining,PAS staining,and Masson staining were used to observe glomerulosclerosis and dilatation of the renal tubule,but the degree of these changes was less than 3 months-old-group,further studies showed that the intrauterine chronic hypoxia group had slightly higher Ang(1-7)concentrations in kidney tissue,the expression of ACE2 m RNA and protein in kidney tissue significantly decreased,when compared with the normal control group.Conclusion Intrauterine chronic hypoxia affects local RAS in the kidneys of adult offspring,leading to imbalance of renal RAS homeostasis,which may cause certain damage to its kidney structure.