Effect Of Apigenin On Reproductive Function Of Male Rats And The Relative Mechanism

Objective To investigate the effect of Apigenin (AP) on male reproductive toxicity and the relative mechanism in order to provide the basis for AP exploitation.Methods 48 adult male Sprague-Dawley rats were divided into four groups randomly. Each group of animals were treated with 234,468,936 mg/kg-bw AP or 10 ml/kg NS respectively by oral gavage for 5 weeks. Blood sample was obtained by cardiac puncture intravital at days 7,14, 21,28 and 35 to examine the concentration of testosterone (T), estradiol (E2), interstitial cell stimulating hormone (ICSH) and follicle-stimulating hormone (FSH). After sacrificing animals, testis and sex accessory organs (epididymis, penis, seminal vesicle, prostate, antiprostate and musculus levator ani) were excised and weighted. Sperm quality was analyzed by WLJY-9000 color semen analysis system. Sperm morphology malformation was counted using optical microscope. Spermatogenic cells cycle were determined by FCM (flow cytometry). Testis histology and transmission electron microscopy (TEM) examination were executed. The activity of testicular total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and the contents of maleic dialdehyde (MDA), glutathione (GSH) were determined. The activities of ACP, AKP, LDH, SDH,NOS, NADPH, Na+K+-ATPase and Ca2+Mg2+-ATPase were determined.Results There are no significant changes of absolute and relative weights of testis, epididymis, penis, seminal vesicle, prostate, antiprostate, musculus levator ani in the 234,468,936 mg/kg-bw AP treatment groups compared with NS group (P>0.05). The grade a sperm density of was decreased significantly and grade d sperm density was noticeably higher than NS controls in the 936 mg/kg·bw AP treatment group (P<0.05). Sperm morphology malformation rate of 936 mg/kg-bw AP treatment group was higher than NS group (P<0.05). Thickness of seminiferous epithelium, arrangement disorder and exfoliation of the seminiferous epithelium, decrease of the number of spermatogenic cells and matured spermatozoa were observed in 936 mg/kg-bw AP treatment groups. TEM examination of sperm ultrastructure revealed that mitochondria in the sperm tail of 936 mg/kg-bw AP treatment group were enlarged/swollen compared with NS control. MDA concentration decreased in 234 mg/kg-bw AP treatment group. The activity of T-AOC increased in 234,468 mg/kg-bw AP treatment group and decreased in 936 mg/kg-bw AP treatment group compared with NS group (P<0.05). The activities of SOD, GSH-Px and the concentration of GSH decreased in AP treatment group compared with NS group (P<0.05). The activities of ACP, AKP and LDH decreased in 234,468,936 mg/kg-bw AP treatment group compared with NS group (P<0.01). The activity of Ca2+Mg2+-ATPase in 234,468,936 mg/kg-bw and Na+K+-ATPase in 936 mg/kg-bw AP treatment group increased compared with NS group (P<0.05). The ratio of T/E2 in 936 mg/kg-bw AP treatment group at day 14,21 and 468 mg/kg-bw AP treatment group at day 28 increased compared with NS group (P<0.05). ICSH increased in 234 mg/kg-bw AP and 936 mg/kg-bw AP treatment groups at day 28 (P<0.05).Conclusion Ap can affect sperm quality decreasing grade a, increasing grade d sperm and sperm morphology malformation rate in male rats. AP damages the structure of seminiferous tubule and mitochondria morphology in sperm. The oxidative stress and the disruption of energy metabolism caused by 936 mg/kg-bw AP probably contribute to the sperm quality decline and seminiferous tubule damage. The mechanism of sex hormone pattern disruption and whether it can affect sperm quality need more research.