The Effect And Mechanism Of Adenosine In The Quality Of Oocyte And Embryo Development

Infertility affects about 10-15% of couples of reproductive age with little change in incidence in the last two decades.Although the in vitro fertilization-embryo transfer(IVF-ET)has made major strides in correcting this condition,there is still plenty of room to improve.Among of those,predict oocyte quality and embryo development reliably and precisely may be a direction.The development of noninvasive omics technology provides a new idea to solve this problem.So we decide to explore the metabolites relevant the high-quality embryos and the effect and mechanism during the embryo development by metabonomics technology.We screened 16 metabolites from the cumulus cells(CCs)corresponding different people high-quality embryo rate.The result showed that adenosine was highly expressed in the CCs,which from the people with the high-quality embryo rate is lower,and adenosine was close to embryo quality,therefore we take it do the further study.We examined the adenosine levels in oocyte and CCs from mice having X-ray or chemotherapy drugs.Results showed that adenosine piled up in both of them,this was consistent with the data in people.Furthermore,the changed m RNA levels in equilibrative nucleoside transporters(ENTs)and concentrative nucleoside transporters(CNTs)indirectly proved the appearance of adenosine concentration difference at inside and outside of cell,there were disorder of adenosine transport by membranes,and caused the incline of adenosine in extracellular environment.Also,adenosine was added in MII culture solution,we found the oocyte quality and embryo development changed,and oxidative stress of oocyte ameliorated,which demonstrated the protection of adenosine contents to oocytes in extracellular environment.But,the m RNA levels of Ents and Cnts in oocytes after adding adenosine did not change obviously,and the adenosine content had not significant upregulate,which proved adenosine does not enter cell by transporters.Next,it is reported that there are adenosine receptors including A1、A2A、A2B and A3,and adenosine works through receptors.In sum,our data suggests that exogenous adenosine works through surface receptor on oocytes.In this study,we screened the adenosine related to high-quality embryo rate in CCs by metabonomics.Then the animal tests confirmed the protection of adenosine to oocyte quality and embryo development,and the expression of transporter gene showed that adenosine works through surface receptor.These open a new area for the application of non-invasive metabonomics to forecast oocyte quality and embryo development,which provided theoretical basis and clinical translation support.