Joint MiRNA/mRNA expression profiling reveals changes consistent with development of dysfunctional corpus luteum after weight gain.

摘要: Obese women exhibit decreased fertility, high miscarriage rates and dysfunctional corpus luteum (CL), but molecular mechanisms are poorly defined. We hypothesized that weight gain induces alterations in CL gene expression. RNA sequencing was used to identify changes the transcriptome vervet monkey (Chlorocebus aethiops) during gain. 10 months of high-fat, high-fructose diet (HFHF) resulted a 20% for HFHF animals vs. 2% controls (p = 0.03) 66% increase percent fat mass group. Ovulation confirmed at baseline after intervention all animals. were collected on luteal day 7–9 based follicular phase estradiol peak. 432 mRNAs 9 miRNAs differentially expressed response diet. Specifically, miR-28, miR-26, let-7b previously shown inhibit sex steroid production human granulosa cells, up-regulated. Using integrated miRNA expression analysis, we demonstrated 52 coordinately regulated mRNA targets corresponding opposite miRNA. 2 miR-28 miR-26 down-regulated, including genes linked development, steroidogenesis, cell proliferation survival. To best our knowledge, this is first report dietary-induced responses ovulating ovary developing adiposity. The observed diet-induced consistent with development provide new mechanistic insights characteristic obese women. MiRNAs may represent novel biomarkers obesity-related subfertility potential avenues therapeutic intervention.