Mitigating Age-Related Ovarian Dysfunction with the Anti-Inflammatory Agent MIT-001.

Ovarian aging is a major obstacle in assisted reproductive medicine because it leads to ovarian dysfunction in women of advanced age. Currently, there are no effective treatments to cure age-related ovarian dysfunction. In this study, we investigated the effect of MIT-001 on the function of aged ovaries. Young and old mice were utilized in this study. MIT-001 was intraperitoneally administered, and the number of follicles and oocytes was analyzed. Each group was then retrieved for RNA and protein isolation. Total RNA was subjected to mRNA next-generation sequencing. Protein extracts from ovarian lysates were used to evaluate various cytokine levels in the ovaries. MIT-001 enhanced follicles and the number of oocytes were compared with non-treated old mice. MIT-001 downregulated immune response-related transcripts and cytokines in the ovaries of old mice. MIT-001 modulates the immune complex responsible for generating inflammatory signals and has the potential to restore the function of old ovaries and improve female fertility.

Lovastatin, an Up-Regulator of Low-Density Lipoprotein Receptor, 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 the low-density lipoprotein receptor (LDLR) enhances oogenesis and follicular development in mouse ovaries. This study investigated whether upregulation of LDLR expression using lovastatin enhances ovarian activity in mice. We performed superovulation using a hormone and used lovastatin to upregulate LDLR. We histologically analyzed the functional activity of lovastatin-treated ovaries and investigated gene and protein expression of follicular development markers, using RT-qPCR and Western blotting. Histological analysis showed that lovastatin significantly increased the numbers of antral follicles and ovulated oocytes per ovary. The in vitro maturation rate was 10% higher for lovastatin-treated ovaries than for control ovaries. Relative LDLR expression was 40% higher in lovastatin-treated ovaries than in control ovaries. Lovastatin significantly increased steroidogenesis in ovaries and promoted the expression of follicular development marker genes such as anti-Mullerian hormone, Oct3/4, Nanog, and Sox2. In conclusion, lovastatin enhanced ovarian activity throughout follicular development. Therefore, we suggest that 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.