Diet-Induced Obesity Alters Granulosa Cell Transcriptome and Ovarian Immune Environment in Mice

Obesity affects female reproductive performance by impairing the ovarian and uterine environments. Using a diet-induced obesity mouse model, we examined whether a high-fat diet (HFD) regimen affects the gene expression profile in ovarian granulosa cells (GCs) and whether short-term HFD has similar effects on gene expression as long-term HFD. C57BL/6J mice were fed a HFD or normal diet (ND) for 16-18 weeks (long-term group) or 4 weeks (short-term group). GCs were collected from each group of mice for RNA-sequencing. RT-PCR and immunofluorescence staining were performed to validate the results. RNA-sequencing analyses of the GCs revealed that several immediate early genes, including <i>early growth response 1</i> (<i>Egr1</i>), an important mediator of ovulation, were significantly downregulated in HFD GCs. <i>Protein tyrosine phosphatase receptor type C</i> (<i>Ptprc</i>) and <i>hematopoietic type prostaglandin D synthase</i> (<i>Hpgds</i>), both of which are associated with increased inflammation, were significantly upregulated in HFD GCs. Downregulation of <i>Egr1</i> was also confirmed in the GCs of short-term HFD mice, suggesting that it constitutes an early change in response to a HFD. Increased expression of several transcription factors in HFD GCs suggests that a HFD may affect the overall transcriptional landscape. The results may indicate possible modulation of the immune environment in HFD ovaries. These results provide novel insights into the molecular changes in GCs in obese environments.