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Gonadotropin-mediated miRNA expression at onset of puberty in rhesus monkey is posited to terminate a hypothyroid state of the testis

ABSTRACT: Goal: To identify small RNA associated with the decision of undifferentiated spermatogonia to commit to a pathway of differentiation. Methods: testis small RNA profiles of 6 juvenile wild-type rhesus monkeys (3 vehicle-treated; 3 gonadotropin treated) were generated by deep sequencing, in triplicate, using Ion Torrent. The sequence reads that passed filters were analyzed with miRDeep2, HTSeq counts and edgeR. qRT–PCR validation was performed using SYBR Green assays Results: We mapped about 3 million sequence reads per sample to the rhesus monkey genome (rheMac 2 and rheMac 8.0.1) and identified 932 small RNAs in the testes of wild type monkeys with Bowtie and miRDeep2 workflow. Approximately a combined 7% of unique transcripts showed differential expression between vehicle and gonadotropin treatment for 48 and 96h, with a fold change ≥1.5 and p value <0.05. Altered expression of 12 genes was confirmed with qRT–PCR, substantiating the RNA-seq findings. Conclusions: The testis transcriptome of the juvenile monkey contained 932 non coding smallRNA. Gonadotropin stimulation for 48 h resulted in the commitment of spermatogonia to differentiate and this was associated with the emergence of 51 differentially expressed genes. Funding support: NIH R01 HD072189 to Tony Plant

ORGANISM(S): Macaca mulatta

PROVIDER: GSE118346 | GEO | 2019/08/08

REPOSITORIES: GEO

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Project description:Obesity is associated with a chronic, low-grade, systemic inflammation that may contribute to the development of insulin resistance and type 2 diabetes. Resveratrol, a natural compound with anti-inflammatory properties, is shown to improve glucose tolerance and insulin sensitivity in obese mice and humans. Here we tested the effect of a 2-year resveratrol administration on the pro-inflammatory profile and insulin resistance caused by a high-fat, high-sugar (HFS) diet in white adipose tissue (WAT) from rhesus monkeys. Eighty mg/day of resveratrol for 12-month followed by 480 mg/day for the second year decreased adipocyte size, increased sirtuin 1 expression, decreased NF-kB activation and improved insulin sensitivity in visceral but not subcutaneous WAT from HFS-fed animals. These effects were reproduced in 3T3-L1 adipocytes cultured in media supplemented with serum from monkeys fed HFS +/- resveratrol diets. In conclusion, chronic administration of resveratrol exerts beneficial metabolic and inflammatory adaptations in visceral WAT from diet-induced obese monkeys. Twenty-four adult (7-13 years old) male rhesus monkeys (Macaca mulatta) were housed individually in standard nonhuman primate caging on a 12h light/12h dark cycle, room temperature (78 +/- 2 degrees F), and humidity at 60 +/- 20%. One pairing was maintained throughout the study; all other monkeys had extensive visual, auditory, and olfactory but limited tactile contact with monkeys housed in the same room. Monkeys received 2 meals per day at estimated ad libitum levels throughout the study. Water was always available ad libitum. Monkeys were monitored minimally 3 times daily by trained animal care staff. During baseline assessments, all monkeys were maintained on a commercially available closed formula monkey chow. After baseline assessment, four male rhesus monkeys remained on the healthy standard diet (SD), 10 male rhesus monkeys were begun on a high fat/high sucrose (HFS) diet and 10 male rhesus monkeys were begun on a high fat/high sucrose (HFS) diet plus Resveratrol, 80mg/day. After one year of dietary intervention, the amount of resveratrol was increased to 480mg/day for one additional year. Tissues were then harvested for the array experiments.

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Gonadotropin-mediated miRNA expression at onset of puberty in rhesus monkey is posited to terminate a hypothyroid state of the testis

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