Kawamura Kazuhiro, Kawamura Nanami, Mulders Sabine M, Sollewijn Gelpke Maarten D, Hsueh Aaron J W
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305-5317, USA.
Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9206-11. doi: 10.1073/pnas.0502442102. Epub 2005 Jun 20.
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.
受精卵向植入前胚胎的最佳发育对生殖至关重要。尽管促黄体生成素(LH)刺激后排卵的哺乳动物卵母细胞可在体外受精并发育成早期胚胎,但对于卵子早期胚胎发育条件的重要卵巢因子知之甚少。由于LH仅与卵巢体细胞相互作用,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,并确定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峰刺激的一种卵巢因子。卵巢BDNF作用于仅在卵母细胞中表达的TrkB受体,以增强卵母细胞的第一极体排出,并促进合子在体外发育成植入前胚胎。此外,用Trk受体抑制剂进行体内治疗可抑制第一极体排出以及合子发育成囊胚的进程。因此,卵巢BDNF对卵母细胞的核成熟和胞质成熟很重要,这对于卵母细胞成功发育成植入前胚胎至关重要。用BDNF处理可使培养的卵母细胞具备向全能囊胚最佳发育进程的条件。