Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA.
Reproduction. 2011 Mar;141(3):313-9. doi: 10.1530/REP-10-0241. Epub 2010 Dec 20.
The molecular basis of human fertilization remains enigmatic. Mouse models are often used to study sperm-egg recognition, but the mouse zona pellucida surrounding ovulated eggs contains three proteins (ZP1, ZP2, and ZP3) whereas the human zona contains four (ZP1, ZP2, ZP3, and ZP4). Human sperm are fastidious and recognize human but not mouse eggs. Transgenic mouse lines were established to ascertain whether human ZP4 is the sole determinant of human sperm binding. Human ZP4 expressed in transgenic mice had a molecular mass similar to the range of native protein isoforms and was incorporated into the extracellular zona matrix. Transgenic females were fertile with normal litter sizes. Mouse sperm readily recognized transgenic ovulated eggs, but human sperm did not. We conclude that human ZP4 is not sufficient to support human sperm binding to the zona pellucida in transgenic mice and that other zona proteins may be needed for human gamete recognition.
人类受精的分子基础仍然扑朔迷离。通常使用小鼠模型来研究精子-卵子识别,但排卵卵周围的小鼠透明带含有三种蛋白质(ZP1、ZP2 和 ZP3),而人类透明带含有四种(ZP1、ZP2、ZP3 和 ZP4)。人类精子很挑剔,只能识别人类卵子,而不能识别小鼠卵子。建立了转基因小鼠系以确定人类 ZP4 是否是人类精子结合的唯一决定因素。在转基因小鼠中表达的人 ZP4 的分子量与天然蛋白同工型的范围相似,并被整合到细胞外透明带基质中。转基因雌性具有正常的产仔数和生育能力。小鼠精子容易识别转基因排卵卵,但人类精子则不能。我们得出结论,人类 ZP4 不足以支持人类精子在转基因小鼠的透明带上结合,并且可能需要其他透明带蛋白来识别人类配子。