| BackgroundReproductive system infection and male infertility is one of the many problems that men face.Infection with different pathogens can interfere with all aspects of male reproduction and lead to infertility.Antibiotics can eliminate pathogens in the reproductive organs and accessory gonads,but antibiotics alone cannot prevent long-term infertility that accompany reproductive inflammation.Previous studies have revealed that lipopolysaccharide(LPS)-induced inflammation adversely affects the male reproductive system through multiple pathways,thereby reducing fertility.Lycopene(LYC)plays a protective role in diseases due to its strong antioxidant capacity,but its role in inflammation-related infertility is poorly studied.The aim of this study was to evaluate the effects of LYC on LPS-induced reproductive damage in male rats.At the same time,the effects of LYC on the plasma and testis of LPS-induced male rats were analyzed by lipidomics and transcriptome analysis to explore the therapeutic mechanism of inflammation-related infertility.MethodsForty male SD rats were rando mly divided into 4 groups:control group,oil group,LPS-group and LYC-group.Rats in the LPS-group and LYC-group were given a single intraperitoneal injection of LPS solution(5mg/kg).24 hours later,rats in the LYC-group were administered with oral LYC solution(5mg/kg)for 4 weeks.Samples were obtained for sperm motility,sperm count,and histological observation of the testis and epididymis.Cytokine levels in serum,testis and epididymis,and indicators of oxidative status were measured.Liquid chromatography-mass spectrometry(LC-MS)was used to detect plasma samples,multivariate statistical analysis was used to screen differential lipids,and the characteristics of plasma lipidomes were evaluated.LC-MS was conducted to analyze the effect of LYC on lipid metabolism in the testis of male rats induced by LPS.RNA sequencing was used to quantitatively analyze gene expression in the testis.The different expressed genes related to the changes in testicular lipid metabolism were identified.Furthermore,bioinformatics analysis was used to screen the key signaling pathways.Spearman’s rank correlation was used to evaluate the correlation between plasma differential lipids and serum cytokines,testicular and epididymal cytokines,and oxidative status indicators.Results1.LYC restored LPS-induced histological and functional injury of testis and epididymis.Meanwhile,LYC significantly reduced LPS-induced overproduction of cytokines in the body,testis and epididymis,ameliorated the elevation of lipid peroxidation products,and improved antioxidant enzyme activity and antioxidant defense capacity,2.LYC changed plasma lipid content and composition,and affected lipid metabolic pathways.These changes were related to anti-inflammatory and anti-oxidation effects.3.LYC-treatment altered testicular lipid metabolism.Combined with RNA sequencing analysis,key signaling pathways related to lipid metabolism were identified,partially explaining the changes in testicular lipid content and composition.4.Correlation analysis found that plasma differential lipids were strongly correlated with cytokines and oxidation status indicators,and sereval lipids could be used as potential biomarkers.ConclusionLYC is an alternative supplement for the treatment stratery of inflammatory injury of the testis and epididymis,which improves the current basic treatment of inflammation-related infertility.Transcriptome and lipidomics analyses reveal the underlying mechanism of LYC on LPS-induced testicular injury,providing new insights and therapeutic targets for the study of the therapeutic mechanism of inflammation-related infertility.The screened plasma differential lipids are potential biomarkers and new therapeutic targets for the treatment of male reproductive tract infection and inflammatory infertility. |
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