Mechanism Of C-phycocyanin Protects Against Low Fertility In Natural Aging Female Mice

The adjustment of birth control policy in China is significance to families planning on delivering the second baby.However,lots of mothers that compliance the policy are older than the best childbearing age.Women over 35 years have higher rates of infertility,largely due to declined number of follicles and deterioration of oocyte quality.Gradual accumulation of oxidative stress damage is considered to be one of the main mechanisms of ovarian aging.Ovarian reactive oxygen species(ROS)with age accumulate continuously and affect the quality of oocyte.Accumulation of ROS inside cells could be prevented by the administration of anti-oxidant medicine.C-Phycocyanin(PC)is a kind of Phycobiliprotein enriched in Spirulina,which has been used as anti-oxidant,anti-inflammatory and radical scavenging.In our previous study,we observed a significant increase in litter size after PC administration in D-galactose-induced aging mice.Further,data obtained with in vivo approach showed that PC can improve oocyte quality,inhibit ROS production,normalize mitochondria distribution,and prevent oocyte apoptosis.Meanwhile,transcriptomics analysis shows that PC can restore some genes expression profile in the ovary in PC administrated mice.However,it is still not known if PC has similar function in natural aging mice.Neither is known about the detailed mechanism of PC's rescue function.By employing the model of natural aging ICR female mice,we investigate PC's effect on ovary and oocyte quality,litter size,as well as offspring development.Moreover,the mechanisms of PC's function in improving fertility were illustrated by testing ovarian antioxidant activity telomere length,telomerase activity and oocyte ROS level,mitochondrial function,apoptosis.Our results showed that PC could improve ovary weight coefficient in aged mice.PC could also increase superoxide dismutase(SOD)activity and decrease methane dicarboxylic aldehyde(MDA)content,and prevent telomere shortening.Meanwhile,PC could significantly promote germinal vesicle breakdown(GVBD),the first polar body(PB1)extrusion,inhibit DNA double-strand breaks and restore the H3K4me2 level in the(Germinal vesicle)GV oocytes.Moreover,PC could facilitate oocytes maturation and fertilization potential.PC has the ability to restore the disordered spindle-chromosome complexs(SCCs),normalize mitochondria distribution as well as decrease the ROS levels and oocytes apoptosis in natural aging mice oocytes,and consequently improve fertility.Overall,our study demonstrated that impaired reproductive capability in aging female mice can be partially rescued by PC through ROS elimination mechanism.This study provides the fundamental data for the application of PC in cure of aging associated female degenerative reproduction.