The Role Of FABP4 In Follicular Fluid Proinflammatory Environment

Objective:The aim of this study is to investigate the association of fatty acid binding protein4（FABP4）with inflammation and lipid metabolism in follicular fluid,and its potential impact on oocyte function.For the first time,we aimed to investigate the clinical relevance of follicular fluid FABP4 with the pro-inflammatory follicular fluid environment of endometriosis（EMs）patients.Methods:In Part1,patients who received antagonist protocol and in vitro fertilization/intracytoplasmic sperm injection-embryo transfer（IVF/ICSI-ET）due to tubal factor/male factor infertility in the Department of Reproductive Medicine,Affiliated Hospital of Qingdao University from June 2020 to January 2021,were recruited in this study（n=122）.According to the follicular fluid FABP4 level,the patients were divided into three groups:group A(≤24.56ng/m L,P₀～P₂₅);group B(24.56～48.36 ng/m L,P₂₆～P₇₅);Group C(>48.36 ng/m L,P₇₆～P₁₀₀).The follicular fluid monocyte chemoattractant protein-1（MCP-1）,interleukin-6（IL-6）,oxidized low-density lipoprotein（ox-LDL）,low-density lipoprotein cholesterol（LDL-C）,triglyceride（TG）and total cholesterol（TC）levels were compared among three groups.Afterwards,the influencing factors of FF FABP4 and the rate of high-quality embryos were analyzed by multivariate linear regression.In Part2,patients with endometriosis-related infertility（EMs group,n=35）was recruited.Patients in control group（n=66）were matched based on the total dosage of gonadotropin（Gn）and BMI with EMs group by SPSS.The level of FABP4,MCP-1,IL-6,ox-LDL,TC,TG and LDL-C in FF of the two groups were compared between the two groups.The clinical correlation between the factors in FF and the rate of high-quality embryos were analyzed by Spearmen correlation respectively.Results:（1）In part1 study population,the level of FF MCP-1,IL-6,and ox-LDL in group A,B and C increased in turn,and the differences among the three groups were statistically significant.There was no significant difference among the three groups in the concentrations of FF LDL-C,TC and TG.（2）The multivariate linear regression analyses revealed that FF FABP4 was independently and negatively correlated with the total usage of Gn,and was independently and positively correlated with FF MCP-1,FF ox-LDL,while has no independent association with FF TC,TG,LDL-C,BMI or HOMA-IR.（3）In Part1 study population,the multivariate linear regression models showed that the total usage of Gn,FF FABP4 and FF IL-6 were independent risk factors for the rate of high-quality embryos,FF ox-LDL and BMI were independent protective factors for the rate of high-quality embryos.The level of estradiol on h CG injection day and antral follicle count were independent protective factors for the number of oocytes obtained.（4）In Part2 study population,the number of oocytes obtained and the rate of high-quality embryos in EMs group were lower than those in the control group,while the group differences were not statistically significant.The level of FF FABP4,ox-LDL,MCP-1and IL-6 in EMs group were significantly higher than the control group（Z=2.145～4.171,P<0.05）;while there was no statistically significant difference in FF TG,TC and LDL-C between two groups.（5）In Part2 study population,Spearman correlation analysis revealed a significant linear positive correlation between FF FABP4 with FF MCP-1(r _EMs=0.5997,P<0.001; r_control=0.567,P<0.0001)and FF ox-LDL(r _EMs=0.5261,P<0.01;r_control=0.6968,P<0.0001)in both EMs group and control group.（6）In the EMs group in Part2,Spearman correlation analysis showed that FF FABP4had no significant linear correlation with the rate of high-quality embryos and the number of oocytes obtained respectively.Conclusion:In this study,we identified for the first time that FF FABP4 might be involved in local inflammation and oxidative stress in follicular fluid,and may be adversely affects the quality of oocytes.Moreover,FF FABP4 level was significantly increased in EMs patients,which may take part in the proinflammation environment in FF by interacting with FF MCP-1 and ox-LDL.