School of Life Sciences and Centre for Cell and Developmental Biology, The Chinese University of Hong Kong, Hong Kong, China.
Biol Reprod. 2011 Nov;85(5):977-86. doi: 10.1095/biolreprod.111.092239. Epub 2011 Jul 6.
The bone morphogenetic proteins (BMPs), originally identified by their abilities to induce bone and/or cartilage formation, have been reported to be involved in various growth and differentiation processes, including reproduction. Although mammalian models are more frequently used to study the BMP system in reproduction, we have extended the study to the zebrafish, an excellent model for studying female reproduction in teleosts. Reverse transcription-PCR analysis revealed the expression of the Bmp ligands (bmp2a, bmp2b, bmp4, bmp6, and bmp7a) and the type II Bmp receptors (bmpr2a and bmpr2b) in various tissues, including the ovary. Spatiotemporal distribution of these Bmp ligands and receptors in the ovary was then investigated in this study. Reverse transcription-PCR on isolated follicle layers and denuded oocytes demonstrated that all Bmp ligands examined were exclusively or abundantly expressed in the oocyte, whereas the two receptors were expressed exclusively in the follicle layers, strongly suggesting a potential paracrine signaling from the oocyte towards the follicle layer by various Bmp ligands. This supports the current view that instead of being passively controlled and nurtured by the follicle layer for its growth and development, the oocyte may play an active role by releasing various growth differentiation factors to regulate follicle layer function. Quantitative analysis of temporal expression profiles during folliculogenesis revealed an increased expression of bmp2a, bmp2b, bmp4, and bmp6 from primary growth (stage I) to previtellogenic (stage II) stages, followed by steady declines toward the end of folliculogenesis when the follicles became fully grown. On the contrast, the BMP receptors (bmpr2a and bmpr2b) consistently showed an increase in expression during folliculogenesis, with the peak levels reached at the full-grown stage prior to final oocyte maturation. The spatiotemporal expression patterns of the Bmp family in the zebrafish follicles provide important insights into potential roles for Bmps during follicle development as oocyte-derived factors. Further experiments using recombinant zebrafish Bmp4 showed that Bmp4 had an inhibitory effect on spontaneous oocyte maturation in vitro, but not 17alpha,20beta-dihydroxy-4-pregnen-3-one (DHP)-induced oocyte maturation in vitro.
骨形态发生蛋白（BMPs）最初因其诱导骨和/或软骨形成的能力而被识别，据报道，它们参与了各种生长和分化过程，包括生殖。虽然哺乳动物模型更常用于研究生殖中的 BMP 系统，但我们已将研究扩展到斑马鱼，这是一种研究硬骨鱼生殖的优秀模型。逆转录-PCR 分析显示，Bmp 配体（bmp2a、bmp2b、bmp4、bmp6 和 bmp7a）和 II 型 Bmp 受体（bmpr2a 和 bmpr2b）在包括卵巢在内的各种组织中表达。本研究随后研究了这些 Bmp 配体和受体在卵巢中的时空分布。对分离的卵泡层和去卵母细胞进行逆转录-PCR 分析表明，所有检测到的 Bmp 配体均仅或大量表达于卵母细胞中，而两个受体仅表达于卵泡层中，这强烈表明各种 Bmp 配体可能通过旁分泌信号从卵母细胞向卵泡层传递信号。这支持了当前的观点，即卵母细胞可能通过释放各种生长分化因子来调节卵泡层功能，从而发挥主动作用，而不是被动地受卵泡层控制和滋养以促进其生长和发育。在卵泡发生过程中进行的时间表达谱的定量分析显示，bmp2a、bmp2b、bmp4 和 bmp6 的表达从初级生长（I 期）到前卵黄生成（II 期）阶段增加，然后在卵泡发生结束时稳定下降，此时卵泡完全生长。相反，BMP 受体（bmpr2a 和 bmpr2b）在卵泡发生过程中表达持续增加，峰值水平在完全生长阶段达到，然后在最终卵母细胞成熟之前达到。斑马鱼卵泡中 Bmp 家族的时空表达模式为 Bmp 在卵泡发育过程中作为卵母细胞来源的因子发挥作用提供了重要线索。进一步使用重组斑马鱼 Bmp4 的实验表明，Bmp4 对体外自发卵母细胞成熟具有抑制作用，但对体外 17alpha,20beta-二羟基-4-孕烯-3-酮（DHP）诱导的卵母细胞成熟没有影响。
