Histol Histopathol, Vol 39, Wassarman and Litscher

Female fertility and the mammalian egg’s zona pellucida

Paul M. Wassarman and Eveline S. Litscher

Deptartment Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, USA

Corresponding Author: Paul M. Wassarman and Eveline S. Litscher, Dept. Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029-6574, USA. e-mail: paul.wassarman@mssm.edu and eveline.litscher@mssm.edu

Summary. All mammalian eggs are surrounded by a relatively thick extracellular matrix (ECM) or zona pellucida (ZP) to which free-swimming sperm bind in a species-restricted manner during fertilization. The ZP consists of either three (e.g., Mus musculus) or four (e.g., Homo sapiens) glycosylated proteins, called ZP1-4. These proteins are unlike those found in somatic cell ECM, are encoded by single-copy genes on different chromosomes, and are well conserved among different mammals. Mammalian ZP proteins are synthesized as polypeptide precursors by growing oocytes that will become ovulated, unfertilized eggs. These precursors are processed to remove a signal-sequence and carboxy-terminal propeptide and are secreted into the extracellular space. Secreted ZP proteins assemble into long, crosslinked filaments that exhibit a structural repeat due to the presence of ZP2-ZP3 dimers every 140 Å or so along filaments. Filaments are crosslinked by ZP1 and are oriented either perpendicular, parallel, or randomly to the plasma membrane of eggs depending on their position in the ZP. Free-swimming mouse sperm recognize and bind to ZP2 or ZP3 that serve as sperm receptors. Acrosome-intact sperm bind to ZP3 oligosaccharides and acrosome-reacted sperm bind to ZP2 polypeptide. ZP filaments fail to assemble in the absence of either nascent ZP2 or ZP3 and results in mouse eggs that lack a ZP and female infertility. Gene sequence variations due to point, missense, or frameshift mutations in genes encoding ZP1-4 results in human eggs that lack a ZP or have an abnormal ZP and female infertility. These and other features of the mouse and human egg’s ZP are discussed here. Histol Histopathol

Key words: Oogenesis, Extracellular Matrix, Female Fertility, Gene Targeting, Gene Sequence Variations, Sperm Binding, Zona Pellucida, ZP Domain, ZP Genes, ZP Proteins, ZP Subdomains

DOI: 10.14670/HH-18-728