Pyrroloquinoline-quinone supplementation restores ovarian function and oocyte quality in a mouse model of advanced maternal age.

Abstract

Natural ovarian aging is one of the major causes for declining fertility in female animals, which has become an insurmountable issue in human reproduction clinics and assisted reproductive technology (ART) procedures. Nevertheless, the molecular basis of oocyte aging remains poorly understood, and feasible improvement strategies are unavailable. In the present study in vivo supplementation of pyrroloquinoline-quinone (PQQ) effectively elevated the fecundity of reproductively aged mice by balancing hormonal secretion, harmonizing the estrus cycle, and eliminating ovarian fibrosis. Moreover, oocyte quality also increased in aged mice after PQQ administration from various aspects, including nuclear and cytoplasmic maturation competency, fertilization capacity and pre-implantation embryonic development potential. Transcriptomic analysis identified target pathways that might mediate PQQ's effects in aged oocytes. Specifically, it was demonstrated that PQQ supplementation restored the mitochondrial dynamics and lysosomal function to remove excessive reactive oxygen species (ROS) and suppress apoptosis in aged oocytes. Jointly, these findings demonstrate PQQ administration is an efficacious method to restore the compromised ovary function and damaged oocyte quality in reproductively aged mice, which might be a potential clinical therapy for women of advanced maternal age with infertility.