Center for Reproductive Medicine, First Affiliated Hospital, Sun Yat-sen University, People's Republic of China.
Eur J Obstet Gynecol Reprod Biol. 2011 Mar;155(1):58-64. doi: 10.1016/j.ejogrb.2010.11.014. Epub 2010 Dec 21.
Controlled ovarian hyperstimulation (COH) results in supraphysiologic levels of maternal serum estradiol (E(2)) during the luteal phase, thus promoting oocyte production at unknown risk to the subsequently developing embryo. Human embryonic stem cells (hESCs) have been identified as a model system to assess the impact of COH on early embryonic development, specifically 17β-estradiol mediated effects on proliferation, gene expression, and histone modification.
Cell proliferation and associated factors, such as HDAC1, as well as histone modification patterns were evaluated in ERα and β expressing hESCs after exposure to 17β-estradiol (1×10(-10) M to 1×10(-7) M), as well as in an untreated control.
Resultant data revealed that while physiologically relevant E(2) levels (1×10(-9)M E(2)) induced cell cycle progression from G1 to the proliferation phase, supraphysiologic levels akin to those observed after COH (1×10(-7) M E(2)) adversely affected hESCs proliferation via down regulation of HDAC1. Modification of H3K9me2, PhH3S10, H4K5ac, and H2A.Z histone patterns were also dependent on 17β-estradiol concentration.
While physiologic levels of 17β-estradiol induced cell proliferation, possibly via HDAC1 involvement in histone modification, cell proliferation in hESCs was suppressed at supraphysiologic levels.
控制性卵巢刺激（COH）会导致黄体期母体血清雌二醇（E（2））水平超生理，从而以未知的风险促进卵母细胞的产生。人类胚胎干细胞（hESC）已被确定为评估 COH 对早期胚胎发育影响的模型系统，特别是 17β-雌二醇对增殖、基因表达和组蛋白修饰的影响。
在暴露于 17β-雌二醇（1×10（-10）M 至 1×10（-7）M）后，以及在未处理的对照中，评估表达 ERα 和β的 hESC 中的细胞增殖和相关因子，如 HDAC1，以及组蛋白修饰模式。
结果数据显示，虽然生理相关的 E（2）水平（1×10（-9）M E（2））诱导细胞从 G1 期进入增殖期，但类似于 COH 后观察到的超生理水平（1×10（-7）M E（2））通过下调 HDAC1 对 hESC 的增殖产生不利影响。H3K9me2、PhH3S10、H4K5ac 和 H2A.Z 组蛋白模式的修饰也依赖于 17β-雌二醇浓度。
虽然生理水平的 17β-雌二醇诱导细胞增殖，可能通过 HDAC1 参与组蛋白修饰，但 hESC 中的细胞增殖在超生理水平时受到抑制。
