Effects of aromatase inhibition on in vitro follicle and oocyte development analyzed by early preantral mouse follicle culture
Effects of aromatase inhibition on in vitro follicle and oocyte development analyzed by early preantral mouse follicle culture
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DOI：
10.1002/mrd.10107
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发表时间：
2002-04-01
影响因子：
2.5
通讯作者：
Smitz, J
中科院分区：
文献类型：
--
作者：
Hu, Y;Cortvrindt, R;Smitz, J
关于卵泡发生的体内研究已经证明了卵泡内类固醇含量、卵泡生长和卵母细胞发育之间的关系。这项研究考察了雄激素/雌激素比例的深刻变化将如何影响小鼠体外卵泡发育。一种有效的滤泡芳香酶抑制剂Arimidex(R)被用于这一目的。腔前早期卵泡培养12天至排卵前。对卵母细胞的减数分裂成熟、纺锤体和染色体构型、体外受精和植入前胚胎发育进行了评价。与对照组相比，Arimidex将卵泡培养液中的E2浓度降低了1000倍，并在条件培养液中测量到预期的同时睾酮积累。Arimidex处理组颗粒细胞提前形成窦状腔，基础孕酮分泌略有增加，卵泡存活率均超过98%，12天卵泡对HCG/EGF均有正常反应，卵丘粘液形成。在绒毛膜促性腺激素排卵挑战中，补充Arimidex的组孕酮产量减少，提示排卵前黄体生成。这些结果表明，在体外，小鼠的卵泡可以在非常低的雌激素水平下正常发育，局部雄激素增加3倍不是自发性的。卵母细胞的生长在不同的培养条件下没有差异。在培养结束时，Arimidex处理组的GVBD和极体形成率呈剂量依赖性增加，纺锤体和染色体分析表明，在所有组中，90%的排出极体的卵母细胞也达到了MII期。虽然大多数培养的MII卵母细胞具有正常的纺锤体和排列良好的染色体，但在含有Arimidex的培养组中，受精的卵母细胞明显较少，但在对照组和Arimidex处理组之间，植入前胚胎的发育没有明显差异。这些数据表明，在小鼠体内，明显的雌激素环境对体外卵泡发生并不是必不可少的。卵泡内类固醇浓度的剧烈变化不会扰乱减数分裂成熟，也不会影响植入前的早期发育，但会对体外培养的卵母细胞的受精产生不利影响，(C)2002年Wiley-Liss公司。
In vivo studies on folliculogenesis have documented a relation among intrafollicular steroid content, follicle growth, and oocyte development. This study examined how profound changes in androgen/estrogen ratio would affect mouse in vitro follicular development. Arimidex(R), a potent follicular aromatase inhibitor was used for this purpose. Early preantral follicles were cultured for 12 days up to the preovulatory stage. Oocyte's meiotic maturation, spindle and chromosome configurations, in vitro fertilization and preimplantation embryo development were evaluated. Compared to controls, Arimidex reduced E2 concentration in follicle culture medium by a factor 1000, and an expected simultaneous accumulation of testosterone was measured in the conditioned medium. Arimidex treatment provoked a dose-dependent earlier differentiation of the granulosa cells as judged by an earlier antrallike cavity formation and slightly elevated basal progesterone secretion, Follicle survival exceeded 98% in all groups and all follicles responded normally to HCG/EGF addition on day 12 by cumulus mucification. By the HCG ovulatory challenge, progesterone output was reduced in Arimidex supplemented groups suggesting preovulatory luteinization. These results indicate that in vitro mouse follicles can develop normally under very low levels of estrogens and that a local androgen increase by a factor 3 is not atretogenic. Oocyte growth did not differ among culture conditions. Arimidex treatment induced a dose dependent enhancement of GVBD and polar body formation rate in response to HCG at the end of culture, Spindle and chromosome analyses demonstrated that in all groups, 90% of the oocytes which extruded a polar body had also reached the MII stage. While most of the cultured MII oocytes had a normal spindle and well aligned chromosomes, significantly less oocytes were fertilized in the groups cultured in the presence of Arimidex, Once fertilized, however, there was found to be no difference for preimplantation embryo development between controls and Arimidex treatment. These data suggest that in mice a pronounced estrogenic environment is not essential for in vitro folliculogenesis. Drastic changes in the intrafollicular steroid concentrations do not disrupt meiotic maturation nor compromise early preimplantation development, but adversely affect fertilization of in vitro grown oocytes, (C) 2002 Wiley-Liss, Inc.