article · International Journal of Molecular Sciences
Obesity induced by a high-fat diet alters gene expression in rat testicular tissue, pointing to clear mechanisms for male infertility. Transcriptome profiling identified 136 differentially expressed genes, with 107 upregulated and 29 downregulated. Upregulated genes include those linked to lipid metabolism, immune response, and aromatase. Increased aromatase activity accelerates the conversion of testosterone to estradiol, depressing the hormone ratio required for normal fertility. Conversely, genes critical to male reproduction, cell adhesion, and olfactory reception are downregulated. Suppression of cadherin junction components promotes the premature release of sperm from Sertoli cells. Furthermore, reduced expression of olfactory receptor genes hinders the chemotactic capacity of sperm to navigate towards the oocyte for fertilisation. These coordinated shifts demonstrate how high-fat diets disrupt testicular cholesterol processing, hormonal balance, and sperm development.
Obesity is a major worldwide health concern frequently linked to male reproductive problems. By identifying the exact molecular pathways disrupted in testicular tissue, this research explains how diet-induced obesity causes male infertility through specific biochemical disruptions, including altered hormone levels, defective sperm maturation, and reduced sperm tracking capability.
This early-stage research provides biological insights that could inform future diagnostic markers for obesity-related reproductive dysfunction and guide the development of anti-obesity drugs. The identified genes offer potential targets for pharmaceutical and diagnostic researchers investigating metabolic disorders and male infertility. As the evidence is restricted to an animal model, any commercial therapeutic or diagnostic application remains at a very early stage of research and development.
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Obesity is a worldwide life-threatening metabolic disorder, associated with various chronic diseases, including male infertility. Obesity was induced by high fat diet (HFD), and testis RNA was used for the transcriptome analysis using RNAseq via Illumina NovaSeq 6000 System and NovaSeq 6000 Kit. Gene expression level was estimated as FPKM (Fragments Per Kilobase of transcript per Million mapped reads). Differential expressed genes (DEGs) were annotated against gene ontology (GO) and KEGG databases. More than 63.66 million reads per sample were performed with 100 bp cutoff and 6 Gb sequencing depth. Results of this study revealed that 267 GO terms (245 biological processes (BP), 14 cellular components (CC), eight molecular functions (MF)), and 89 KEGG pathways were significantly enriched. Moreover, total numbers of 136 genes were differentially expressed (107 upregulated, 29 downregulated) with |FC| ≥ 2 and bh adjusted <0.05. Interesting DEGs were detected, including obesity and lipid metabolism-related genes, immune response-related genes, cytochrome P450 genes, including aromatase were upregulated, whereas genes related to male fertility and fertilization, cell adhesion, and olfactory receptors were downregulated. The combined expression pattern of the DEGs in obese animals indicated an increase in cholesterol metabolism. Furthermore, high aromatase activity enhances the testosterone turnover into estradiol and lowers the testosterone/estradiol (T/E) ratio, which ultimately reduces fertility. In addition, downregulation of cadherens junction components genes leads to the pre-mature release of sperm from Sertoli cells resulting in the reduction of fertility. Moreover, the downregulation of olfactory receptor genes reduces the chemotaxis capacity of sperms in tracking the oocyte for fertilization, which reduces male fertility. Furthermore, various obesity molecular markers were detected in our transcriptome. The results of this study will enhance our understanding of the molecular network of obesity development, development of obesity novel molecular diagnosis markers, molecular bases of obesity-induced infertility, and the development of anti-obesity drugs.
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DOI: 10.3390/ijms21186493
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