Effects Of VDR On Reproduction And Lipid Metabolism And Regulates The Expression Of Related Genes In Male Mice

Vitamin D receptor?VDR?is a nuclear transcription factor and belongs to steroid hormone/thyroid hormone receptor superfamily.VDR was found to be expressed by different germ cells such as Leydig cells,supporting cells and sperm cells.It shows the close relationship between VDR and male reproduction.In this study,significantly reduced reproductive performance and less adipose tissue around testis were found in VDR^-/-male mice.Based on previous studies,we speculate that VDR affects the lipid metabolism in reproductive system and reproductive system of mice.In this experiment,VDR^-/-male mice were used as study object,and WT male mice were used as controls.HE staining and oil red O staining were used to reveal the microstructure of the reproductive system.And the results were used to evaluate the effects of VDR on male reproduction and lipid metabolism.The physiological mechanism of reproductive decline and abnormal lipid metabolism in VDR^-/-male mice was studied through sperm quality evaluation,serum androgen and lipid content analysis.The pathways and genes related to lipid metabolism were screened from RNA-seq data and were used to study the molecular mechanisms of VDR affecting reproductive and lipid metabolism from the tissue,cellular,and molecular levels.Our research results will provide theoretical basis for the treatment of male reproductive disorders and the study of pathological mechanism.The main experimental results obtained in this study are as follows:1.VDR^-/-male mice were found to have abnormal reproductive system development and significantly reduced reproductive performance.The decrease of sperm quality,androgen synthesis,abnormal reproductive system and lipid metabolism may be the reasons for the decrease of reproductive performance in VDR^-/-male mice.2.The argument that VDR may affect lipid metabolism in male mice has been confirmed by the fact that VDR^-/-male mice have fewer lipids in their blood and fewer lipid droplets in Leydig cells.PPAR and four others significantly altered pathways and four genes related to lipid metabolism,including Fabp4,SCD-1,Angptl4 and LPL,affected by VDR,were screened from RNA-seq data and qPCR validation.Our study suggests that VDR may regulate lipid metabolism in mice by affecting the expression of genes related to PPAR pathway.3.The cAMP-PKA signaling pathway may be involved in the regulation of androgen synthesis by VDR.The molecular mechanism of VDR regulating lipid metabolism pathway may be that it inhibits the transcription of LPL and promotes the transcription of FABP4,Angptl4,SCD-1 and FKBP51.4.The protein interaction between FKBP51 and VDR was verified by Co-IP.The expression level of FKBP51 is positively correlated with VDR,and FKBP51 has the same effect on androgen synthesis pathway as VDR.The results of this study indicate that FKBP51may bind to VDR protein and participate in the regulation of male reproduction.