Abstract Rhesus macaques ( Macaca mulatta , RMs) are widely used in sexual maturation studies due to their high genetic and physiological similarity to humans. However, judging sexual maturity in captive RMs based on blood physiological indicators, female menstruation, and male ejaculation behavior can be inaccurate. Here, we explored changes in RMs before and after sexual maturation based on multi-omics analysis and identified markers for determining sexual maturity. We found that differentially expressed microbiota, metabolites, and genes before and after sexual maturation showed many potential correlations. Specifically, genes involved in spermatogenesis ( TSSK2 , HSP90AA1 , S OX5 , SPAG16 , and SPATC1 ) were up-regulated in male macaques, and significant changes in gene ( CD36 ), metabolites (cholesterol, 7-ketolithocholic acid, and 12-ketolithocholic acid), and microbiota ( Lactobacillus ) related to cholesterol metabolism were also found, suggesting the sexually mature males have stronger sperm fertility and cholesterol metabolism compared to sexually immature males. In female macaques, most differences before and after sexual maturity were related to tryptophan metabolism, including changes in IDO1 , IDO2 , IFNGR2 , IL1Β , IL10 , L-tryptophan, kynurenic acid (KA), indole-3-acetic acid (IAA), indoleacetaldehyde, and Bifidobacteria , indicating that sexually mature females exhibit stronger neuromodulation and intestinal immunity than sexually immature females. Cholesterol metabolism-related changes ( CD36 , 7-ketolithocholic acid, 12-ketolithocholic acid) were also observed in female and male macaques. Exploring differences before and after sexual maturation through multi-omics, we identified potential biomarkers of sexual maturity in RMs, including Lactobacillus (for males) and Bifidobacterium (for females) valuable for RM breeding and sexual maturation research. 

Multi-omics analysis reveals changes in tryptophan and cholesterol metabolism before and after sexual maturation in captive macaques

The prevalence of diabetes mellitus has been increasing for decades worldwide. To develop safe and potent therapeutics, animal models contribute a lot to the studies of the mechanisms underlying its pathogenesis. Dietary induction using is a well-accepted protocol in generating insulin resistance and diabetes models. In the present study, we reported the multi-omics profiling of the liver and sera from both peripheral blood and hepatic portal vein blood from Macaca fascicularis that spontaneously developed Type-2 diabetes mellitus with a chow diet (sDM). The other two groups of the monkeys fed with chow diet and high-fat high-sugar (HFHS) diet, respectively, were included for comparison. Analyses of various omics datasets revealed the alterations of high consistency. Between the sDM and HFHS monkeys, both the similar and unique alterations in the lipid metabolism have been demonstrated from metabolomic, transcriptomic, and proteomic data repeatedly. The comparison of the proteome and transcriptome confirmed the involvement of fatty acid binding protein 4 (FABP4) in the diet-induced pathogenesis of diabetes in macaques. Furthermore, the commonly changed genes between spontaneous diabetes and HFHS diet-induced prediabetes suggested that the alterations in the intra- and extracellular structural proteins and cell migration in the liver might mediate the HFHS diet induction of diabetes mellitus.

Fancheng Tan

Papers

Multi-Omics Comparison of the Spontaneous Diabetes Mellitus and Diet-Induced Prediabetic Macaque Models