The effect of lovastatin as up-regulated lipoprotein metabolism enhances follicular development in mouse ovaries.

Ovarian aging hampers in vitro fertilization in assisted reproductive medicine and has no cure. Lipoprotein metabolism is associated with ovarian aging. It remains unclear how to overcome poor follicular development with aging. Upregulation of low-density lipoprotein receptor (LDLR) enhances oogenesis and follicular development in mouse ovaries. Therefore, we investigated whether lovastatin enhances LDLR expression in mouse ovaries and analyzed oogenesis and follicular development in lovastatin-treated mouse ovaries. We performed superovulation using a hormone and used lovastatin to upregulate LDLR. We histologically analyzed functional activity of lovastatin-treated ovaries and investigated gene and protein expression of follicular development markers, using RT-qPCR and western blotting. Relative LDLR expression was 40% higher in lovastatin-treated ovaries than in control ovaries. Histological data reveal significantly increased the antral follicles and ovulated follicles in the Lovastatin treated ovary. Therefore, lovastatin treatment enhanced both the gonadotrophin-independent and -dependent phases upon hormone hyperstimulation as well as gene and protein expression of follicular development and ovarian function markers. Lovastatin significantly increased steroidogenesis in ovaries and promoted expression of follicular development marker genes such as anti-Mullerian hormone, Oct3/4, Nanog, and Sox2. Lovastatin enhanced ovarian activity throughout follicular development. Therefore, upregulation of LDLR may help to improve follicular development in clinical settings. Modulation of lipoprotein metabolism can be used with assisted reproductive technologies to overcome ovarian aging.