The Predictive Role Of ADAMTS1 And HSPG2 MRNA Levels In Human Cumulus Cells For Oocyte Developmental Competence

Objective:The aim of this study was to determine the correlation of the expression level of ADAMTS1 and HSPG2 in the cumulus cells(CCs)and controlled ovarian hyperstimulation(COH)outcomes,and to explore whether it could be used as a potential biomarker.Methods:The experiments are divided into 3 parts in this study.The first part is basic research on C57BL/6 mice.CCs in different timepoints after h CG injection(0h,4h,8h,12 h and 16h)were collected to perform RT-PCR.At the same time,si RNA was used to interfere the expression of ADAMTS1,the RT-PCR was used to test the relationship of ADAMTS1 and HSPG2.The second and third parts are retrospective analysis of human cumulus cells.Women with PCOS(N=45)and normal ovulatory controls(N=103)undergoing IVF/ICSI were recruited.The relative ADAMTS1 and HSPG2 m RNA levels were measured by quantitative RT-PCR.Moreover,correlations of ADAMTS1 and HSPG2 levels with COH outcomes were analyzed.Results:1.During mice ovulation,the m RNA level of ADAMTS1 was increased and reached a peak at 12 h after injecting h CG and then was significantly decreased,whereas the expression pattern of HSPG2 was opposite to ADAMTS1 with the lowest level at 12 h.2.The PCOS group compared with normal ovulatory women had lower ADAMTS1 and higher HSPG2 expression levels with a significantly lower fertilization rate(64.345 ± 0.359% vs.85.502 ± 0.147%,P<0.0001).3.In normal ovulatory women undergoing COH,a higher expression of ADAMTS1 was associated with higher numbers of matured oocytes,transplantable embryos and good quality embryo number(13.000 ± 0.101 vs.10.692 ± 0.073,P=0.0335;7.137 ± 0.077 vs.5.385 ± 0.059,P=0.0137;3.863 ± 0.053 vs.2.462 ± 0.037,P=0.0097).A lower HSPG2 expression was correlated with more matured oocytes,more transplantable embryo,more good quality embryo,higher transplantable embryo rates and good quality embryo rates(12.192 ± 0.091 vs.11.471 ± 0.089,P=0.0474)(6.962 ± 0.067 vs.5.529 ± 2.471,P=0.045;3.827 ± 0.048 vs.2.471 ± 0.044,P=0.0047;85.217 ± 0.311% vs.68.600 ± 0.545%,P=0.0004;45.850 ± 0.444% vs.29.734 ± 0.436%,P=0.0005).The ROC curve suggests us that co-consideration of ADAMTS1 and HSPG2 in CCs could be potential biomarkers of oocyte quality.Conclusions:In PCOS and normal ovulatory patients,higher ADAMTS1 and lower HSPG2 expression levels in cumulus cells are related to better COH outcomes.ADAMTS1 is positively correlated with oocyte quality,while HSPG2 is negatively correlated with oocyte quality.