自身代谢缓解甲氨蝶呤对小鼠体内成熟卵母细胞副作用的研究

甲氨蝶呤(methotrexate,MTX)作为抗叶酸代谢类药物,在临床上应用广泛。其副作用之一表现为损伤卵母细胞质量。那么,对于有妊娠需求的女性服药者,停药后多久才适合受孕呢?该文结合双光子荧光成像与三维重构技术研究此问题。通过单次腹腔注射生理盐水及5 mg/kg MTX建立了对照组和MTX组小鼠,随后建立了MTX注射后代谢5、10、15、20、25及30天组小鼠。研究发现,小鼠体内成熟卵母细胞的纺锤体正常形态比率与染色体正常空间排布比率,分别于代谢15天和25天后,显著高于MTX组,并恢复至对照组水平。表征卵母细胞功能的体外受精率、二细胞胚胎率及囊胚率,发现分别于代谢15、20、25天后,恢复至对照组水平。该文结果表明,自身代谢可恢复MTX所引起的卵母细胞质量受损及功能下降,所需时间约为小鼠的5个生理周期,即25天。

Study on Self-Metabolism Alleviating Side-Effects of Methotrexate on the Mouse in-Vivo Matured Oocytes

MTX(methotrexate),an anti-folate drug,has been widely used in clinic.One of the side-effects of MTX is to reduce the quality of oocytes.So,how long it may take for the female patients with pregnancy needs to get pregnant after stopping taking MTX?In this paper,two-photon fluorescence imaging and three-dimensional reconstruction were combined to force on this issue.The model of mice in the control and MTX groups were established by intraperitoneally injecting physiological saline and 5 mg/kg MTX,and then the mice in the self-metabolism groups were established via metabolism lasting for five,10,15,20,25 and 30 days after MTX injection.It was found that the rate of normal spindle morphology and the rate of normal chromosome arrangement in the mouse in-vivo matured oocytes were significantly higher than those in the MTX group and returned to the levels of the control group after 15 and 25 days of metabolism,respectively.The in-vitro fertilization rate,two-cell embryo rate and blastocyst rate,which were used to characterized the function of oocytes,returned to the levels in the control group after 15,20 and 25 days of metabolism,respectively.It indicated that self-metabolism could recover the MTX-induced quality impairment and functional decline of oocytes,and the recovery time was about five physiological cycles of mice,namely 25 days.