TAF4b, a TBP associated factor, is required for oocyte development and function

TAF4b, a TBP associated factor, is required for oocyte development and function
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DOI:
10.1016/j.ydbio.2005.09.038
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发表时间:
2005-12-15
影响因子:
2.7
通讯作者:
Richards, JS
Richards, JS
中科院分区:
生物学3区
文献类型:
--
作者:
Falender, AE;Shimada, M;Richards, JS

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可受精卵母细胞的发育是一个复杂的过程,依赖于特定基因在生殖细胞和周围体细胞中的精确时空表达。由于TBP相关因子Taf4b缺失的雌性小鼠是不育的,我们试图确定在卵泡发育期间首次观察到这种表型的时间。出生后第3天,Taf4b缺失型雌性小鼠的卵巢卵母细胞数明显少于野生型和杂合子Taf4b小鼠(P<0.01)。然而,在第15天,卵巢中只有一个体细胞标记Fox12的表达减少。尽管卵泡数量减少,但许多卵泡进入窦状期,与颗粒细胞分化和卵母细胞成熟相关的多个基因在正常模式下表达,未成熟的Taf4b基因缺失的雌性可以在激素刺激下排卵和交配。然而,Taf4b基因缺失小鼠排出的卵丘卵母细胞复合体含有较少的(P&lt;0.01)卵丘细胞,卵母细胞功能异常。GVBD和极体排出量显著减少(P&lt;0.01)。少数受精的卵母细胞未能超过两细胞发育阶段。因此,Taf4b基因缺失的雌性小鼠的不孕症与排卵和受精后早期卵泡形成、卵母细胞成熟和合子卵裂的缺陷有关。(C)2005 Elsevier Inc.保留所有权利。
Development bf a fertilizable oocyte is a complex process that relies on the precise temporal and spatial expression of specific genes in germ cells and in surrounding somatic cells. Since female mice null for Taf4b, a TBP associated factor, are sterile, we sought to determine when during follicular development this phenotype was first observed. At postnatal day 3, ovaries of Taf4b null females contained fewer (P < 0.01) oocytes than ovaries of wild type and heterozygous Taf4b mice. However, expression of only one somatic cell marker Fox12 was reduced in ovaries at day 15. Despite the reduced number of follicles, many proceed to the antral stage, multiple genes associated with granulosa cell differentiation and oocyte maturation were expressed in a normal pattern, and immature Taf4b null females could be hormonally primed to ovulate and mate. However, the ovulated cumulus oocyte complexes from the Taf4b null mice had fewer (P < 0.01) cumulus cells, and the oocytes were functionally abnormal. GVBD and polar body extrusion were reduced significantly (P < 0.01). The few oocytes that were fertilized failed to progress beyond the two-cell stage of development. Thus, infertility in Taf4b null female mice is associated with defects in early follicle formation, oocyte maturation, and zygotic cleavage following ovulation and fertilization. (c) 2005 Elsevier Inc. All rights reserved.