Gonadotropin and intra-ovarian signals regulating follicle development and atresia: the delicate balance between life and death
Gonadotropin and intra-ovarian signals regulating follicle development and atresia: the delicate balance between life and death
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DOI：
10.2741/2339
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发表时间：
2007-05-01
影响因子：
3.1
通讯作者：
Tsang, Benjamin K.
中科院分区：
文献类型：
--
作者：
Craig, Jesse;Orisaka, Makoto;Tsang, Benjamin K.
哺乳动物卵泡发育受细胞死亡和存活信号的严格调控，包括内分泌（如促性腺激素）和卵巢内调节因子（如Nodal和GDF9）。单个卵泡的命运（生长/排卵或闭锁）取决于促进卵泡细胞增殖、生长和分化的因子以及促进程序性细胞死亡（凋亡）的因子在表达和作用上的微妙平衡。从原始卵泡到窦前卵泡阶段的卵泡发育受卵母细胞衍生因子包括GDF9和BMP15的调控，且不依赖促性腺激素的支持（促性腺激素非依赖阶段）。当卵泡进入早期窦卵泡阶段时，它对促性腺激素产生反应（促性腺激素反应阶段），进一步发育使卵泡完全依赖促性腺激素的存在，同时受卵巢内调节因子的调节（促性腺激素依赖）。卵泡命运也受促凋亡因子如卵巢内调节因子Nodal的调控，Nodal由卵泡膜细胞分泌，通过涉及Smad2信号传导和抑制PI3K/Akt通路的机制促进分化的颗粒细胞凋亡。细胞内蛋白 prohibitin（PHB）在卵泡发生过程中似乎具有双重作用；在未分化细胞中作为细胞存活因子，在分化后作为促凋亡因子。对这些内分泌和卵巢调节因子之间相互作用的进一步研究将有助于更好地理解卵泡发育和闭锁的调控，从而为辅助生殖开发新技术。
Regulation of mammalian follicular development is tightly regulated by both cell death and survival signals, including endocrine (e.g. gonadotropin) and intra-ovarian regulators (e.g. Nodal and GDF9). The destiny of the individual follicle (growth/ovulation or atresia) is dependent on a delicate balance in the expression and action of factors promoting follicular cell proliferation, growth and differentiation, and of those promoting programmed cell death (apoptosis). Development of the follicle from the primordial to preantral stage is regulated by oocyte-derived factors including GDF9 and BMP15, and is not dependent on gonadotropin support (gonadotropin-independent stage). As the follicle transits into the early antral stage it becomes responsive to gonadotropin (gonadotropin-responsive stages) and further development renders the follicle completely dependent on the presence of gonadotropin while modulated by intra-ovarian regulators (gonadotropin-dependent). Follicle fate is also regulated by pro-apoptotic factors such as the intraovarian regulator Nodal, which is secreted by the theca and promotes apoptosis of differentiated granulosa cells through a mechanism involving Smad2 signaling and suppression of the PI3K/Akt pathway. The intracellular protein prohibitin (PHB) appears to have a dual role during folliculogenesis; acting as a cell survival factor in undifferentiated cells, and as a pro-apoptotic factor following differentiation. Further investigations of the interplay between these endocrine and ovarian regulators will lead to a better understanding into the regulation of follicular development and atresia, allowing development of new techniques for assisted reproduction.