Abstract
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.
Highlights
Obesity is one of the modern health risks worldwide with increasing prevalence in all societies
More than 6.5 billion bases were read in the raw data ranging from 6.5 (C2) to 8.1 (O2) billion bases across samples, whereas above 6.4 billion bases in the trimmed data ranging from 6.4 (C2) to 8.0 (O2)
It causes the depletion of testosterone by activation of cholesterol metabolism for producing bile acids in the liver to meet the excessive fat digestion and high conversion of testosterone to estradiol in the testis
Summary
Obesity is one of the modern health risks worldwide with increasing prevalence in all societies. It has been substantially increased over the last four decades [1,2]. Obesity is considered a vital predisposing risk factor for various chronic diseases, such as type-2 diabetes, insulin resistance, hypertension, dyslipidemia, chronic inflammation, cancer, cardiovascular diseases, and infertility [5,6,7,8]. These obesity-associated metabolic disorders are involved in increased mortality and morbidity rates [5]. It is well established that there are several important signaling pathways linking obesity to the immune system [9]
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