A Co-expression Analysis Of Endometrial Transcriptome In Association With Female Obesity

In recent years,the incidence of obesity has increased significantly around the world and caused widespread concern.Obese people have an increased risk of metabolic diseases,cardiovascular and cerebrovascular diseases,asthma,and osteoarthritis,which not only affect the long-term quality of life of humans,but are also associated with reproductive health.Studies on female body mass index and pregnancy outcomes indicate that female overweight/obesity significantly affects the pregnancy outcomes of first fresh embryo transfer.Moreover,the cumulative live birth rate(CLBR)is also compromised after fresh and subsequent frozen-thawed embryo transfer.There is no specific mechanism declaring the adverse effects of female BMI on pregnancy outcome.Endometrial function plays an important role for successful embryo implantation,and compromised endometrial receptivity among obese women is thought to be important factor,leading to lower implantation rate and decreased IVF success rate.The traditional method to evaluate the endometrial receptivity depends on morphological criteria,while its predictive value for the success of clinical pregnancy is very limited.Bioinformatics have achieved great improvement nowadays,especially in the field of tumors,providing a new method to explore the molecular mechanisms of disease.Objectives1.Use the GSE58144 dataset to explore the endometrial transcriptomics characteristics of obese women in mid-secretory phase;2.Utilize the differential expression analysis methods to confirm whether endometrial receptive marker genes are differentially expressed among different BMI groups,and then analyze the potential molecular mechanism of female obesity in association with endometrial dysfunction.Materials and Methods1.The GSE58144 dataset was obtained using the GEO public database,including 72 samples from infertile subject with an unsuccessful IVF/ICSI cycle,and the weighted gene co-expression network analysis(WGCNA)method was used to select modules associated with obesity.The modules that are significantly related to the obesity phenotype and the hub genes within the modules were screened and subjected to GO/KEGG enrichment analysis.2.Utilize the differential expression analysis via limma software package to screen out the differentially expressed genes in the mid-secretory phase endometrium among three BMI groups,and the STRING database was used to perform PPI networks on the differentially expressed genes between the obese and non-obese groups.Results1.In the co-expression network analysis,results indicated that turquoise,magenta,and yellow modules are significantly related to obesity.Genes within turquoise module are positively correlated with obesity,which were involved in fatty acids metabolism,cholesterol metabolism and transmembrane transport of substances.The hub genes selected from these modules including DUOX1/DUOXA1 and BMP7.These genes are up-regulated in the WOI endometrium of obese women,mainly involved in ROS metabolic process,oxidative stress,and endometrial decidualization.2.The results from differentially expressed gene analysis demonstrated that 11 endometrial receptive marker genes were significantly down-regulated in WOI endometrial tissues of obese women;among the marker genes,glycodelin(PAEP)and glutathione peroxidase(GPX3)were involved in regulating the biological processes of endometrial immune tolerance and cellular antioxidant damage.In addition,the antioxidant enzyme superoxide dismutase 2(SOD2)in the obese group WOI endometrium was also significantly down-regulated.ConclusionsFemale obesity might restrain the endometrial decidualization and endometrial immune tolerance in mid-secretory phase,and disturb the balance of the intracellular oxidative-antioxidant system by increasing the production of ROS and intracellular oxidative stress,leading to endometrial dysfunction in window of implantation and finally reducing the ART success rate.