Effects Of Daidzein On Oligospermia Via Prostaglandin E2 Metabolism

BackgroundIn recent years,the prevalence of infertility in the world is increasing,with male factors accounting for about 30%.Oligozoospermia is one of the major causes of male infertility.Daidzein is one of the phytoestrogen isoflavones,and humans have a wide range of contact with them in daily life through the consumption of beans and soy products.Since its structure is similar to endogenous estrogens,it can bind to estrogen receptors in vivo and generate estrogenic effects,which affects many health aspects of human,including male reproductive health.There are few studies on the effects of daidzein on male reproduction up to now,and the conclusions of these studies are not consistent.Further studies should be carried out to explore the association and mechanism.ObjectiveVerify the correlation between daidzein exposure and oligozoospermia and explore the mechanism.MethodsA population-based case-control study was conducted to verify the correlation between daidzein exposure and oligospermia.Metabolism analysis of the human urine revealed the possible mechanism of daidzein-induced oligozoospermia.After being exposed to daidzein for 12 weeks in adolescent C576L/6J mice model at the low dose(1 mg/kg/day),high dose(100 mg/kg/day),and the combination of daidzein(100 mg/kg/day)and aspirin(5 mg/kg/day),a prostaglandin E2 synthesis inhibitor,male mouse were mated with normal female mouse and the reproductive outcomes were observed at the 18 th day of the gestation.The transcriptomics and metabolomics analysis were performed to explore the mechanism.ResultsCase-control study had shown a positive correlation between daidzein exposure and spermatogenesis disorder or oligozoospermia.The metabolism analysis of human urine revealed that the effect may be caused via prostaglandin E2 metabolism.The results of animal experiments showed that daidzein exposure affects the organ coefficient and sperm density.In the mating experiment with normal female mice,the uterine embryo weight of mated females and the number of live fetuses in experimental group were decreased significantly.Interestingly,the above results could be reversed by aspirin.Finally,metabolomics combined with transcriptomoics methods were used to explore the underlying mechanisms.It was found that daidzein increased the prostaglandin E2 level by up-regulating the expression of Pla2g6 enzyme and Ptges3 enzyme gene in testis.Prostaglandin E2 affected the fumarate acid and the gene expression of Pck1 enzyme and Ass1 enzyme,which lead to the disturbances of the TCA cycle,gluconeogenesis and urea cycle,and ultimately exerted oligospermia.ConclusionThere is a positive correlation between daidzein exposure and oligozoospermia,and it may be caused via the interference of prostaglandin E2 metabolism.