Enriched expression of lipid biosynthetic genes in follicle‐depleted mouse ovaries

Abstract

An ovary‐intact mouse model for menopause has been developed using the chemical 4‐vinylcyclohexene diepoxide (VCD) which causes gradual ovarian failure (OF) by accelerating follicular atresia. This study was designed to compare gene expression in residual ovarian tissue of VCD‐treated mice to that of cycling controls while taking into consideration potential direct effects of VCD dosing. Mice were dosed daily (20d) with vehicle (sesame oil; n=12) or VCD (i.p; n=30). On d105, VCD‐treated mice were divided into 2 groups (n=10/group): follicle‐depleted (FD) and follicle‐depleted + VCD (VCD) and dosed for 15d. Ovaries were collected 24h after last day of the second VCD dosing and processed for microarray analysis (n=4/group). The abundance of mRNAs encoding fatty acid binding protein 3 (Fabp3), branched chain aminotransferase 2 (Bcat2), panthotenate kinase 4 (Pank4), enoyl CoA hydratase 1 (Echs1) and acetyl‐CoA dehydrogenase (Acadl) was greater (P<0.05) in FD and VCD compared to cycling controls. There were no differences (P>0.05) in expression of all genes between FD and VCD. Enriched expression of genes involved in lipid biosynthesis suggests a role for residual ovarian tissue in the regulation of cholesterol, lipids and fatty acids. Moreover, there was no evidence for direct effects of VCD on residual ovarian tissue, thus furthering the VCD‐treated mouse as a relevant model for menopause (AG021948).