Wang Yajun, Ge Wei
Department of Biology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
Biol Reprod. 2003 Dec;69(6):1998-2006. doi: 10.1095/biolreprod.103.020826. Epub 2003 Aug 20.
We have previously demonstrated that activin is likely an ovarian mediator of pituitary gonadotropin(s) and local epidermal growth factor in their stimulating oocyte maturation and maturational competence in the zebrafish. However, the downstream events controlled by activin remain unknown. One possible mechanism is that activin may directly work on the oocytes to promote the development of oocyte maturational competence. To substantiate this hypothesis, we performed the present study to demonstrate the expression of the activin system in different compartments of zebrafish follicles, namely, the follicle cells and oocytes. The proteins examined include activin subunits (betaA and betaB), activin-binding protein (follistatin), activin type II receptors (type IIA and IIB), the type I activin receptor-like kinases (ALK1-like, ALK2-like, and ALK4-like), and the intracellular activin signaling molecules (Smad2, Smad3, Smad4, and Smad7). The results showed that the entire activin signaling system is expressed by the full-grown immature zebrafish oocytes ( approximately 0.65 mm in diameter), including ALK4-like (ActRIB), ALK2-like (ActRIA), ActRIIA, ActRIIB, Smad2, Smad3, Smad4, and Smad7, therefore supporting our hypothesis that the oocytes are one of the direct targets of activin actions in the zebrafish ovary. In contrast, activin itself (betaA and betaB) and ALK1-like type I receptor are predominantly expressed in the follicle cells surrounding the oocytes. Interestingly, although follistatin is expressed in both the follicle cells and oocytes, its level of expression is significantly higher in the oocytes than the follicle cells, implying that follistatin may serve as a signal from the oocytes to modulate the activity of activin produced by the follicle cells. Taken together, the present study provides convincing evidence that although all members of the activin system are expressed in the whole follicle, they exhibit distinct spatial patterns of expression among different compartments of the follicle. It is likely that activin works directly on the oocytes in a paracrine manner to promote oocyte maturation and maturational competence. On the other hand, instead of being controlled passively by the follicle cells, the oocytes may actively participate in the regulation of follicle development by releasing various modulating molecules such as follistatin.
我们之前已经证明，在斑马鱼中，激活素可能是垂体促性腺激素和局部表皮生长因子刺激卵母细胞成熟及其成熟能力的卵巢介质。然而，激活素所控制的下游事件仍然未知。一种可能的机制是，激活素可能直接作用于卵母细胞，以促进卵母细胞成熟能力的发展。为了证实这一假设，我们进行了本研究，以证明激活素系统在斑马鱼卵泡的不同部分，即卵泡细胞和卵母细胞中的表达。所检测的蛋白质包括激活素亚基（βA和βB）、激活素结合蛋白（卵泡抑素）、激活素II型受体（IIA型和IIB型）、I型激活素受体样激酶（ALK1样、ALK2样和ALK4样）以及细胞内激活素信号分子（Smad2、Smad3、Smad4和Smad7）。结果表明，整个激活素信号系统在完全成熟的未成熟斑马鱼卵母细胞（直径约0.65毫米）中表达，包括ALK4样（ActRIB）、ALK2样（ActRIA）、ActRIIA、ActRIIB、Smad2、Smad3、Smad4和Smad7，因此支持了我们的假设，即卵母细胞是斑马鱼卵巢中激活素作用的直接靶点之一。相比之下，激活素本身（βA和βB）和ALK1样I型受体主要在围绕卵母细胞的卵泡细胞中表达。有趣的是，尽管卵泡抑素在卵泡细胞和卵母细胞中均有表达，但其在卵母细胞中的表达水平明显高于卵泡细胞，这意味着卵泡抑素可能作为来自卵母细胞的信号来调节卵泡细胞产生的激活素的活性。综上所述，本研究提供了令人信服的证据，即尽管激活素系统的所有成员都在整个卵泡中表达，但它们在卵泡的不同部分表现出不同的空间表达模式。激活素可能以旁分泌方式直接作用于卵母细胞，以促进卵母细胞成熟及其成熟能力。另一方面，卵母细胞可能通过释放各种调节分子（如卵泡抑素），而不是被动地受卵泡细胞控制，积极参与卵泡发育的调节。
