Sato A, Otsu E, Negishi H, Utsunomiya T, Arima T
St Luke Clinic, Tsumori, Oita, Japan.
Hum Reprod. 2007 Jan;22(1):26-35. doi: 10.1093/humrep/del316. Epub 2006 Aug 21.
There is an increased incidence of rare imprinting disorders associated with assisted reproduction technologies (ARTs). The sex-specific epigenetic modifications that are imposed during gametogenesis act as a primary imprint to distinguish maternal and paternal alleles. The most likely candidate for the gametic mark is DNA methylation. However, the timing of DNA methylation acquisition in adult oocytogenesis and the effects of superovulation are unknown.
We examined the maternal methylation of PEG1(MEST), LIT1(KCNQ1OT1) and ZAC(PLAGL1) and the paternal methylation of H19 in adult growing oocytes of humans and mice and compared them with the methylation status of mouse neonatal growing oocytes by using bisulphite sequencing. Furthermore, we examined the effects of superovulation in the human and mouse.
Maternal methylation of these genes has already been initiated to some extent in adult human and mouse non-growing oocytes but not in mouse neonates. In addition, the methylation dynamics during adult human and mouse oocyte development changed more gradually than those during neonatal oocyte development. Furthermore, we found the demethylation of PEG1 in growing oocytes from some ART-treated infertile women and a gain in the methylation of H19. We also detected methylation changes in superovulated mice.
Our studies in the human and mouse suggest that superovulation can lead to the production of oocytes without their correct primary imprint and highlight the need for more research into ARTs.
与辅助生殖技术（ART）相关的罕见印记疾病发病率有所上升。配子发生过程中施加的性别特异性表观遗传修饰作为主要印记来区分母本和父本等位基因。配子标记最可能的候选者是DNA甲基化。然而，成年卵母细胞发生过程中DNA甲基化获得的时间以及超排卵的影响尚不清楚。
我们通过亚硫酸氢盐测序检测了人类和小鼠成年生长中卵母细胞中PEG1（MEST）、LIT1（KCNQ1OT1）和ZAC（PLAGL1）的母本甲基化以及H19的父本甲基化，并将其与小鼠新生生长中卵母细胞的甲基化状态进行比较。此外，我们研究了超排卵对人类和小鼠的影响。
这些基因的母本甲基化在成年人类和小鼠的非生长卵母细胞中已在一定程度上启动，但在小鼠新生儿中未启动。此外，成年人类和小鼠卵母细胞发育过程中的甲基化动态变化比新生儿卵母细胞发育过程中的变化更为渐进。此外，我们发现一些接受ART治疗的不孕妇女的生长中卵母细胞中PEG1发生去甲基化，而H19的甲基化增加。我们还在超排卵小鼠中检测到甲基化变化。
我们在人类和小鼠中的研究表明，超排卵可导致产生没有正确初级印记的卵母细胞，并强调需要对ART进行更多研究。
