Oocyte-specific genes regulate follicle formation, fertility and early mouse development

Oocyte-specific genes regulate follicle formation, fertility and early mouse development
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DOI:
10.1016/s0165-0378(01)00100-0
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发表时间:
2002-01-01
影响因子:
3.4
通讯作者:
Dean, J
Dean, J
中科院分区:
医学4区
文献类型:
--
作者:
Dean, J

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卵母细胞表达的基因产物在卵泡发生、受精和着床前发育中起重要作用。生殖系因子α(图α)是一种碱性螺旋-环-螺旋(bHLH)转录因子,首次在E13.5的卵母细胞中检测到,并在成人中持续存在。缺乏FlG α的雌性小鼠不能形成原始卵泡,这导致卵母细胞的大量消耗和不育。FlGa也是表达编码ZP 1、ZP 2和ZP 3的透明质酸基因所必需的。缺乏ZP 1的小鼠形成结构异常的带状物并具有降低的生殖力。缺乏ZP 3的小鼠尽管存在其他两种β-淀粉样蛋白,但没有β-淀粉样蛋白基质。尽管Zp 3基因敲除小鼠中发生卵泡发生,但排卵很少,雌性小鼠不育。将表达人ZP 3的转基因小鼠与Zp 3缺失小鼠杂交,并重建嵌合透明基质(moZP 1、moZP 2、moZP 3)。出乎意料的是,人类精子在体外不能与“人源化”透明带结合,但小鼠精子可以。虽然在卵子发生的后期,卵母细胞变得转录失活,母体RNA被降解,但早期发育的激活需要来自卵子的预先存在的母体产物。胚胎所需的母体抗原(Mater)是一种单拷贝基因,在生长的卵母细胞中转录,尽管其转录物在减数分裂成熟过程中降解,但MATER蛋白仍存在于胚泡中。缺乏这种125 kDa细胞质蛋白的雌性小鼠由于早期卵裂阶段的胚胎阻滞而不产生后代。因此,Hater代表了哺乳动物发育中少数记录的母性效应基因之一,由Elsevier Science爱尔兰Ltd.出版。
Gene products expressed in oocytes play important roles in folliculogenesis, fertilization and pre-implantation development. Factor in the Germline, alpha (FIG alpha) is a basic helix-loop-helix (bHLH) transcription factor first detected in oocytes at E13.5 that persists in adults. Female mice lacking FlG alpha are unable to form primordial follicles which results in massive depletion of oocytes and sterility. FlGa is also required for expression of the zona pellucida genes that encode ZP1, ZP2, and ZP3. Mice lacking ZP1 form structurally abnormal zonae and have decreased fecundity. Mice lacking ZP3 have no zona matrix despite the presence of the other two zona proteins. Although, folliculogenesis occurs in Zp3 null mice, few eggs are ovulated and females are sterile. Transgenic mice expressing human ZP3 have been crossed with Zp3 null mice and reconstitute a chimeric zona pellucida matrix (moZP1, moZP2, moZP3). Unexpectedly, human sperm do not bind to 'humanized' zonae pellucidae in vitro, but mouse sperm do. Although, late in oogenesis, oocytes becomes transcriptionally inactive and maternal RNA is degraded, the activation of early development requires pre-existing maternal products from the egg. Maternal antigen that embryos require (Mater) is a single-copy gene that is transcribed in growing oocytes and, although its transcripts are degraded during meiotic maturation, MATER protein persists into the blastocyst. Female mice lacking this 125 kDa cytoplasmic protein produce no off-spring because of an embryonic block at the early cleavage stage. Thus, Hater represents one of the few documented maternal effect genes in mammalian development, Published by Elsevier Science Ireland Ltd.