Effects Of AKR7A5 Gene Knockout On The Development In Male Mice

Aldo-keto reductase(AKR)7A5 is a member of the superfamily of aldo-keto reductases(AKRs),which can reduce a variety of aldehydes or ketones in the body to the corresponding less toxic or non-toxic ones.alcohol,thereby protecting the body from damage by toxic aldehydes or ketones.Using the AKR7A5 gene knockout mouse model,the liver and kidney tissue cell morphology and organ coefficients of wild-type mice and AKR7A5 gene knockout mice were analyzed,and an acute alcoholic liver injury model was constructed to analyze related enzyme activities and protein profiles,revealing the effects of AKR7A5 gene on liver and kidney function in mice;The preliminary epididymal differential proteomics studies in the laboratory suggest that AKR7A5 may play an important role in the testis,The study revealed the effect of AKR7A5 gene on the reproductive system of male mice by studying the cell morphology and organ coefficient of testis and epididymis in mice,and measuring sperm motility and fertility.In this paper,the effects of AKR7A5 gene on the development of male mice were studied through the two parts of liver,kidney and reproductive system.The results were as follows:1.AKR7A5 knockout homozygous mice were successfully bred by co-caging AKR7A5 knockout heterozygous mice;analysis of the growth curves of mice from 1～40days after birth showed that AKR7A5 knockout and wild-type mice were the overall trend of changes in body weight was the same.2.The testicular and epididymal coefficients of mice were measured,and it was found that there was not statistically significant between the AKR7A5 gene knockout type and the wild-type mice(P>0.05).The testis and epididymal tissue sections showed that the testis and epididymal cells of the two groups of mice were normal;sperm the motility assay found that the epididymal sperm concentration,total number of linear forward migration,linear motility sperm(PM),forward motility sperm ratio(PR),and average curvilinear velocity(VCL)in AKR7A5 knockout mice were significantly lower than those in wild-type mice(P<0.01),the proportion of immotile sperm(IM)was significantly higher than that of wild-type mice(P<0.01).The 4-month fertility test showed that the average litter size,litter size and litter size of AKR7A5 knockout mice were significantly higher than those of wild-type mice(P<0.01).There was no significant difference in wild-type mice(P>0.05);however,the total litter size was significantly lower than those in wild-type mice(P<0.01).3.Determination of the coefficients of the heart,liver,spleen,lung and kidney of the mice showed that the AKR7A5 gene knockout type was not statistically significant compared with the wild-type mice(P>0.05).Pathological section results showed that AKR7A5 gene knockout mice’s liver and kidney tissues have certain cell necrosis.4.The model of acute alcohol liver injury in mice was successfully constructed,and the mice were divided into 4 groups according to whether alcohol was intragastric or not,namely,knockout blank group and wild-type blank group(fed with water),knockout treatment group and wild-type treatment group(fed with alcohol).Liver morphology observation showed that the liver color of wild-type blank group was normal as jujube red,while the liver color of the other three groups became light yellow.Enzyme activity assay showed that compared with wild-type blank group,the levels of alkaline phosphatase(AKP)and glutamic-oxalacetic transaminase(GOT)in wild-type treatment group were significantly increased(P<0.01),and the levels of glutathione GSH and lipid oxidation(MDA)were significantly decreased(P<0.01).In the determination of AKP and GSH enzyme activities,the change trend of the knockout blank group was consistent with that of the wild-type treatment group,which had statistical significance.The protein concentration of treatment group was higher than that of control group(P<0.05),and the activity of glutamic-pyruvic transaminase(GPT)showed no significant difference among all groups.The protein profile results showed that the difference proteins between the wild-type treatment group and the wild-type blank group were mainly concentrated in retinol metabolism,steroid hormone biosynthesis,RNA transport,arachidonic acid metabolism,ribosomes,lysosomes,splicing the biological processes are mainly concentrated in the metabolic process of monocarboxylic acid and protein transport;the difference proteins between the knockout blank group and the wild type blank group are mainly concentrated in peroxisomes,lysosomes,chemical carcinogenesis,ribosomes,RNA degradation,Metabolic pathways,biological processes are mainly concentrated in purine nucleotide metabolism and protein transport;the difference proteins between the knockout treatment group and the knockout blank group are mainly concentrated in terpenoid backbone biosynthesis,galactose metabolism,metabolic pathways,ribosomes,Lysosomes,spliceosomes,and biological processes are mainly concentrated in fatty acid metabolism and transport of organic matter and nitrogen complexes.In conclusion,we speculated that AKR7A5 gene has a certain role in the reproductive capacity and antioxidant damage of liver and kidney tissues of male mice.