Litscher Eveline S, Wassarman Paul M
Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029-6574, USA.
Trends Dev Biol. 2020;13:21-33.
The zona pellucida (ZP) is an extracellular matrix (ECM) that surrounds all mammalian oocytes, eggs, and embryos and plays vital roles during oogenesis, fertilization, and preimplantation development. The mouse and human ZP is composed of three or four unique proteins, respectively, called ZP1-4, that are synthesized, processed, and secreted by oocytes during their growth phase. All ZP proteins have a zona pellucida domain (ZPD) that consists of ≈270 amino acids and has 8 conserved Cys residues present as four intramolecular disulfides. Secreted ZP proteins assemble into long fibrils around growing oocytes with ZP2-ZP3 dimers located periodically along the fibrils. The fibrils are cross-linked by ZP1 to form a thick, transparent ECM to which sperm must first bind and then penetrate during fertilization of eggs. Inactivation of mouse or by gene targeting affects both ZP formation around oocytes and fertility. Female mice with eggs that lack a ZP due to inactivation of either or are completely infertile, whereas inactivation of results in construction of an abnormal ZP and reduced fertility. Results of a large number of studies of infertile female patients strongly suggest that gene sequence variations (GSV) in human or due to point, missense, or frameshift mutations have similar deleterious effects on ZP formation and female fertility. These findings are discussed in light of our current knowledge of ZP protein synthesis, processing, secretion, and assembly.
透明带（ZP）是一种细胞外基质（ECM），它包围着所有哺乳动物的卵母细胞、卵子和胚胎，并在卵子发生、受精和植入前发育过程中发挥重要作用。小鼠和人类的透明带分别由三种或四种独特的蛋白质组成，称为ZP1 - 4，它们在卵母细胞生长阶段由卵母细胞合成、加工和分泌。所有ZP蛋白都有一个透明带结构域（ZPD），该结构域由约270个氨基酸组成，有8个保守的半胱氨酸残基，以四个分子内二硫键的形式存在。分泌的ZP蛋白在生长中的卵母细胞周围组装成长纤维，ZP2 - ZP3二聚体沿纤维周期性定位。这些纤维通过ZP1交联形成一个厚的、透明的细胞外基质，精子在卵子受精时必须首先结合并穿透该基质。通过基因靶向使小鼠的 或 失活会影响卵母细胞周围的ZP形成和生育能力。由于 或 失活而缺乏ZP的雌性小鼠的卵子完全不育，而 的失活会导致异常ZP的构建和生育能力降低。对不孕女性患者的大量研究结果强烈表明，由于点突变、错义突变或移码突变导致的人类 或 中的基因序列变异（GSV）对ZP形成和女性生育能力有类似的有害影响。根据我们目前对ZP蛋白合成、加工、分泌和组装的了解，对这些发现进行了讨论。
