The injections of mitochondrial fusion promoter M1 during proestrus disrupt the progesterone secretion and the estrous cycle in the mouse

Abstract

After ovulation, the mitochondrial enzyme CYP11A1 cleavage the cholesterol into pregnenolone for progesterone synthesis, suggesting that mitochondrial dynamics play a vital role in the female reproductive system. The changes in the mitochondria dynamics throughout the ovarian cycle have been reported in literature, but the correlation to its role in the ovarian cycle remains unclear. In this study, mitochondrial fusion promotor, M1, was used to study the impact of mitochondria dynamics in the female reproductive system. Our results showed that M1 treatment in mice can lead to the disruptions of estrous cycles in vagina smears. The decrease in serum LH was recorded in the animal. And the inhibitions of progesterone secretion and ovulations were observed in ovarian culture. Although no significant changes in mitochondrial networks were observed in the ovaries, significant up-regulation of mitochondrial respiratory complexes was revealed in M1 treatments through transcriptomic analysis. In contrast to the estrogen and steroid biosynthesis up-regulated in M1, the molecules of extracellular matrix, remodeling enzymes, and adhesion signalings were decreased. Collectively, our study provides novel targets to regulate the ovarian cycles through the mitochondria. However, more studies are still necessary to provide the functional connections between mitochondria and the female reproductive systems.