Defective zonae pellucidae in Zp2-null mice disrupt folliculogenesis, fertility and development.
Defective zonae pellucidae in Zp2-null mice disrupt folliculogenesis, fertility and development.
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发表时间：
2001-04
期刊：
影响因子：
4.6
通讯作者：
T. Rankin;M. O'Brien;Eric Lee;K. Wigglesworth;J. Eppig;Jurrien Dean
中科院分区：
文献类型：
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作者：
T. Rankin;M. O'Brien;Eric Lee;K. Wigglesworth;J. Eppig;Jurrien Dean
所有的脊椎动物卵都被细胞外基质所包围。这种基质在哺乳动物中被称为透明质酸，对于生长中的卵母细胞的存活、成功受精和早期胚胎通过输卵管至关重要。小鼠透明质酸由三种糖蛋白（ZP 1、ZP 2和ZP 3）组成，每种糖蛋白由单拷贝基因编码。在胚胎干细胞中使用靶向诱变，已经建立了Zp 2缺失小鼠系。ZP 1和ZP 3蛋白继续合成，并在早期卵泡中形成薄的基质，而在排卵前卵泡中不持续。异常的卵泡基质不影响初始卵泡的发生，但从缺乏透明卵泡的小鼠分离的卵巢中，有腔期卵泡的数量显著减少。用促性腺激素刺激后，在输卵管中检测到很少的卵子，并且在将Zp 2缺失的雌性小鼠与正常雄性小鼠交配后，没有回收到两细胞胚胎。结构缺陷比Zp 1缺失小鼠中观察到的更严重，Zp 1缺失小鼠具有降低的生殖力，但不像Zp 3缺失小鼠中观察到的那么严重，Zp 3缺失小鼠从不形成可见的透明细胞并且是不育的。尽管体外成熟和受精的无透明带卵母细胞可以进展到囊胚阶段，但来自Zp 2-或Zp 3-无效卵的囊胚的发育潜力似乎受到损害，并且在转移到寄养母亲后，未观察到活产。因此，除了其在受精和保护早期胚胎中的作用外，这些数据与透明质酸在卵泡发生期间维持颗粒细胞和卵母细胞之间的相互作用是一致的，这对于最大化卵母细胞的发育能力至关重要。
All vertebrate eggs are surrounded by an extracellular matrix. This matrix is known as the zona pellucida in mammals and is critically important for the survival of growing oocytes, successful fertilization and the passage of early embryos through the oviduct. The mouse zona pellucida is composed of three glycoproteins (ZP1, ZP2 and ZP3), each encoded by a single copy gene. Using targeted mutagenesis in embryonic stem cells, Zp2-null mouse lines have been established. ZP1 and ZP3 proteins continue to be synthesized and form a thin zona matrix in early follicles that is not sustained in pre-ovulatory follicles. The abnormal zona matrix does not affect initial folliculogenesis, but there is a significant decrease in the number of antral stage follicles in ovaries isolated from mice lacking a zona pellucida. Few eggs are detected in the oviduct after stimulation with gonadotropins, and no two-cell embryos are recovered after mating Zp2-null females with normal male mice. The structural defect is more severe than that observed in Zp1-null mice, which have decreased fecundity, but not quite as severe as that observed in Zp3-null mice, which never form a visible zona pellucida and are sterile. Although zona-free oocytes matured and fertilized in vitro can progress to the blastocyst stage, the developmental potential of blastocysts derived from either Zp2- or Zp3-null eggs appears compromised and, after transfer to foster mothers, live births have not been observed. Thus, in addition to its role in fertilization and protection of early embryos, these data are consistent with the zona pellucida maintaining interactions between granulosa cells and oocytes during folliculogenesis that are critical to maximize developmental competence of oocytes.