Ovarian brain-derived neurotrophic factor (BDNF) promotes the development of oocytes into preimplantation embryos
Ovarian brain-derived neurotrophic factor (BDNF) promotes the development of oocytes into preimplantation embryos
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DOI：
10.1073/pnas.0502442102
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发表时间：
2005-06-28
影响因子：
11.1
通讯作者：
Hsueh, AJW
中科院分区：
文献类型：
--
作者：
Kawamura, K;Kawamura, N;Hsueh, AJW
受精卵最佳发育成植入前胚胎对于繁殖至关重要。尽管在黄体生成素（LH）刺激后排卵的哺乳动物卵母细胞可以在体外受精并促进形成早期胚胎，但对于调节卵子以促进早期胚胎发育的重要卵巢因素知之甚少。由于 LH 仅与卵巢体细胞相互作用，因此其对卵母细胞功能的潜在调节可能是由局部旁分泌因子介导的。我们对卵巢转录本进行了 DNA 微阵列分析，并鉴定出颗粒细胞和卵丘细胞分泌的脑源性神经营养因子 (BDNF) 是排卵前 LH 激增刺激的卵巢因子。卵巢BDNF作用于卵母细胞中专门表达的TrkB受体，以增强卵母细胞的第一极体挤出并促进受精卵在体外发育成植入前胚胎。此外，Trk受体抑制剂的体内治疗抑制了第一极体挤出和受精卵向囊胚的进展。因此，卵巢 BDNF 对卵母细胞的核和细胞质成熟很重要，这对于卵母细胞成功发育成植入前胚胎至关重要。 BDNF 治疗可以调节培养的卵母细胞，使其最佳地进展为全能囊胚。
Optimal development of fertilized eggs into preimplantation embryos is essential for reproduction. Although mammalian oocytes ovulated after luteinizing hormone (LH) stimulation can be fertilized and promoted into early embryos in vitro, little is known about ovarian factors important for the conditioning of eggs for early embryo development. Because LH interacts only with ovarian somatic cells, its potential regulation of oocyte functions is presumably mediated by local paracrine factors. We performed DNA microarray analyses of ovarian transcripts and identified brain-derived neurotrophic factor (BDNF) secreted by granulosa and cumulus cells as an ovarian factor stimulated by the preovulatory LH surge. Ovarian BDNF acts on TrkB receptors expressed exclusively in oocytes to enhance first polar body extrusion of oocytes and to promote the in vitro development of zygotes into preimplantation embryos. Furthermore, in vivo treatment with a Trk receptor inhibitor suppressed first polar body extrusion and the progression of zygotes into blastocysts. Thus, ovarian BDNF is important to nuclear and cytoplasmic maturation of the oocyte, which is essential for successful oocyte development into preimplantation embryos. Treatment with BDNF could condition the cultured oocytes for optimal progression into the totipotent blastocysts.