精索静脉曲张导致不孕。目前的研究已经调查了实验性精索静脉曲张对DNA甲基化的影响,去甲基化,和生殖细胞的损伤,TESE来源和附睾精子。此外,比较了表皮细胞和TESE来源的精子的结果。最后,评估了精索静脉曲张对男性原核活性DNA去甲基化(ADD)和植入前胚胎发育的影响.将成年雄性大鼠分为对照组,对照假手术(经过简单的剖腹手术),和实验性精索静脉曲张诱导组(每组n=6)。左肾静脉半结扎被认为是诱发精索静脉曲张。DNA甲基转移酶1(DNMT1)和十11易位蛋白(TET1,2,3)的表达水平,和睾丸组织中的全局DNA甲基化,TESE,附睾衍生的精子,并评估了受精卵雄性原核中的ADD以及植入前胚胎发育。DNMT1和TET1、2、3在睾丸中的表达水平,TESE,与对照组和假手术组相比,精索静脉曲张组的附睾精子减少。与附睾衍生的精子相比,TESE衍生的精子表现出更高的DNMT1,更高的DNMT1和TET1、2,并且TET3表达没有变化。精索静脉曲张组代表睾丸中DNA甲基化较低,TESE来源和附睾精子,男性原核中5mC+信号较高,与对照和对照假大鼠相比,植入前胚胎发育较低。与附睾精子相比,TESE衍生的精子表现出更高的5mC蛋白表达。总之,精索静脉曲张会对DNA甲基化/去甲基化过程产生负面影响,损害精子发生并导致受精失败,这最终可能会通过增加对DNA损伤的敏感性而导致胚胎发育下降。
Varicocele causes infertility. The current study has investigated the impact of experimental varicocele on DNA methylation, demethylation, and damage in the germ cells, TESE-derived and epididymal spermatozoa. Moreover, the results were compared between epidydimal and TESE-derived spermatozoa. Finally, the varicocele-induced effect on active DNA demethylation (ADD) of male pronucleus and pre-implantation embryo development was assessed. The mature male rats were divided into control, control-sham (undergone simple laparotomy), and experimental varicocele-induced groups (n = 6/each group). The left renal vein semi-ligation was considered to induce varicocele. The expression levels of DNA methyltransferase 1 (DNMT1) and ten-eleven-translocation proteins (TET1, 2, 3), and global DNA methylation in testicular tissue, TESE, and epididymis-derived spermatozoa, and the ADD in zygotes male pronucleus as well as pre-implantation embryo development were assessed. The expression levels of DNMT1 and TET1, 2, 3 in testicles, TESE, and epididymis-derived spermatozoa were decreased in the varicocele group compared to the control and control-sham groups. The TESE-derived spermatozoa exhibited higher DNMT1, higher DNMT1, and TET 1, 2, and no change in TET3 expression compared to epididymis-derived spermatozoa. The varicocele group represented lower DNA methylation in the testicles, TESE-derived and epididymal spermatozoa, higher 5mC+ signal in male pronucleus, and a lower pre-implantation embryo development compared to control and control-sham rats. The TESE-derived spermatozoa exhibited higher 5mC protein expression compared to epididymal spermatozoa. In conclusion, varicocele can negatively impact the DNA methylation/demethylation processes impairing spermatogenesis and leading to fertilization failure, which may ultimately result in a decrease in embryo development by increasing susceptibility to DNA damage.