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Effect of Dietetic Obesity on Testicular Transcriptome in Cynomolgus Monkeys
Yanru Zhang1, Jia Qi1, Juan Zhao1,2
1Laboratory Animal Center, Xi'an Jiaotong University Health Science Centre, Xi'an 710061, China.
Abstract:
Obesity is a metabolic disorder resulting from behavioral, environmental and heritable causes, and can have a negative impact on male reproduction. There have been few experiments in mice, rats, and rabbits on the effects of obesity on reproduction, which has inhibited the development of better treatments for male subfertility caused by obesity. Nonhuman primates are most similar to human beings in anatomy, physiology, metabolism, and biochemistry and are appropriate subjects for obesity studies. In this investigation, we conducted a transcriptome analysis of the testes of cynomolgus monkeys on high-fat, high-fructose, and cholesterol-rich diets to determine the effect of obesity on gene expression in testes. The results showed that the testes of obese monkeys had abnormal morphology, and their testes transcriptome was significantly different from that of non-obese animals. We identified 507 differentially abundant genes (adjusted p value < 0.01, log2 [FC] > 2) including 163 up-regulated and 344 down-regulated genes. Among the differentially abundant genes were ten regulatory genes, including IRF1, IRF6, HERC5, HERC6, IFIH1, IFIT2, IFIT5, IFI35, RSAD2, and UBQLNL. Gene ontology (GO) and KEGG pathway analysis was conducted, and we found that processes and pathways associated with the blood testes barrier (BTB), immunity, inflammation, and DNA methylation in gametes were preferentially enriched. We also found abnormal expression of genes related to infertility (TDRD5, CLCN2, MORC1, RFX8, SOHLH1, IL2RB, MCIDAS, ZPBP, NFIA, PTPN11, TSC22D3, MAPK6, PLCB1, DCUN1D1, LPIN1, and GATM) and down-regulation of testosterone in monkeys with dietetic obesity. This work not only provides an important reference for research and treatment on male infertility caused by obesity, but also valuable insights into the effects of diet on gene expression in testes.
Insights
Obesity negatively impacts male fertility. Transcriptome analysis in obese monkeys revealed abnormal testicular morphology and gene expression changes, including pathways related to immunity and DNA methylation, offering insights into male subfertility.
Area of Science:
- Reproductive Biology
- Metabolic Disorders
- Genomics
Background:
- Obesity, a metabolic disorder with diverse causes, adversely affects male reproductive health.
- Previous studies on obesity's reproductive effects in rodents are limited; nonhuman primates offer greater physiological similarity to humans.
- Understanding diet-induced obesity's impact on testicular gene expression is crucial for addressing male subfertility.
Purpose of the Study:
- To investigate the effects of a high-fat, high-fructose, and cholesterol-rich diet on testicular gene expression in cynomolgus monkeys.
- To identify differentially abundant genes and enriched pathways in the testes of obese monkeys compared to non-obese controls.
Main Methods:
- Transcriptome analysis of testicular tissue from cynomolgus monkeys fed obesogenic diets.
- Identification of differentially abundant genes using adjusted p-value < 0.01 and log2 [FC] > 2 thresholds.
- Gene Ontology (GO) and KEGG pathway analysis to determine functional enrichment.
Main Results:
- Obese monkeys exhibited abnormal testicular morphology and significant differences in testicular transcriptome compared to non-obese counterparts.
- 507 differentially abundant genes were identified, including 163 up-regulated and 344 down-regulated genes, with notable regulatory genes identified.
- Enriched pathways included those related to the blood-testes barrier (BTB), immunity, inflammation, and DNA methylation. Genes associated with infertility and reduced testosterone levels were also observed.
Conclusions:
- Diet-induced obesity significantly alters testicular gene expression and morphology in nonhuman primates.
- Key pathways affected include those regulating immune response, inflammation, and gamete DNA methylation, potentially contributing to male infertility.
- This study provides a valuable reference for understanding and treating male subfertility linked to obesity and dietary factors.
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