Brain-derived neurotrophic factor is a regulator of human oocyte maturation and early embryo development

Brain-derived neurotrophic factor is a regulator of human oocyte maturation and early embryo development
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DOI:
10.1016/j.fertnstert.2009.04.007
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发表时间:
2010-03-15
影响因子:
6.7
通讯作者:
De Sousa, Paul A.
De Sousa, Paul A.
中科院分区:
医学2区
文献类型:
--
作者:
Anderson, Richard A.;Bayne, Rosemary A. L.;De Sousa, Paul A.

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目的:研究脑源性神经营养因子(BDNF)在人类卵母细胞成熟中的作用。设计:前瞻性研究。设置:研究机构。患者:接受腹腔镜绝育的女性。干预:在含有激素(H; FSH,LH,E-2)和血清替代品(SR)的培养基中,将小窦卵泡卵丘卵母细胞复合体(COCs)体外成熟(IVM)至中期II(MII)。BDNF或BDNF的阻断抗体主要结果测量:分析COCs的神经营养因子配体/受体和卵丘基因的表达,(HAS 2,TNFAIP 6,PTGS 2,GREM 1),卵丘扩增,成熟为MII,孤雌胚胎发育。BDNF和TrkB受体在卵丘和成熟卵母细胞中表达。在对照(H + SR)与H + BDNF、H + SR + BDNF或BDNF + SR培养基中IVM后MII产量没有差异。然而,BDNF/AB和TrkB/Fc都提高了MII产率。激活后,H + SR中的正常切割最高(38%),而阻断抗体产生最高的异常切割(BDNF/AB 68%; TrkB/Fc 57%)。在H + BDNF + SR中切割失败率最高(92%)。只有H + SR产生桑椹胚/囊胚(6%)。结论:COCs中的BDNF信号通路影响卵母细胞的成熟和早期胚胎的发生。(Fertil Steril(R)2010;93:1394-406.(C)2010年由美国生殖医学学会。
Objective: To investigate a role for brain-derived neurotrophic factor (BDNF) in human oocyte maturation.Design: Prospective study.Setting: Research institute.Patients: Women undergoing laparoscopic sterilization.Intervention(s): Small antral follicle cumulus oocyte complexes (COCs) were matured in vitro (IVM) to metaphase II (MII) in media with hormones (H; FSH, LH, E-2), serum replacement (SR). BDNF, or blocking antibodies to BDNF (BDNF/AB and TrkB/Fc), and activated.Main Outcome Measure(s): The COCs were analyzed for expression of neurotrophin ligands/receptors and cumulus genes (HAS2, TNFAIP6, PTGS2, GREM1) by reverse transcription polymerase chain reaction (RT-PCR), cumulus expansion, maturation to MII, and parthenogenetic embryo development.Result(s): The BDNF and truncated TrkB receptor were expressed in cumulus and mature oocytes. There was no difference in MII yields after IVM in control (H + SR) versus H + BDNF, H + SR + BDNF, or BDNF + SR media. However, both BDNF/AB and TrkB/Fc improved MII yields. After activation, normal cleavage was highest in H + SR (38%), whereas blocking antibodies yielded the highest abnormal cleavage (BDNF/AB 68%; TrkB/Fc 57%). Failure to cleave was highest in H + BDNF + SR (92%). Only H + SR yielded morulae/blastocysts (6%). Expression of GREM1 in cumulus increased after IVM in H + BDNF versus H + SR or in vivo maturation.Conclusion(s): The BDNF signaling within COCs influences oocyte maturation and early embryogenesis. (Fertil Steril (R) 2010;93:1394-406. (C)2010 by American Society for Reproductive Medicine.)