Zona Pellucida Genes and Proteins: Essential Players in Mammalian Oogenesis and Fertility
All mammalian oocytes and eggs are surrounded by a relatively thick extracellular matrix (ECM), the zona pellucida (ZP), that plays vital roles during oogenesis, fertilization, and preimplantation development. Unlike ECM surrounding somatic cells, the ZP is composed of only a few glycosylated protei...
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MDPI AG
2021-08-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/8/1266 |
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| author | Paul M. Wassarman Eveline S. Litscher |
| author_facet | Paul M. Wassarman Eveline S. Litscher |
| author_sort | Paul M. Wassarman |
| collection | DOAJ |
| description | All mammalian oocytes and eggs are surrounded by a relatively thick extracellular matrix (ECM), the zona pellucida (ZP), that plays vital roles during oogenesis, fertilization, and preimplantation development. Unlike ECM surrounding somatic cells, the ZP is composed of only a few glycosylated proteins, ZP1–4, that are unique to oocytes and eggs. ZP1–4 have a large region of polypeptide, the ZP domain (ZPD), consisting of two subdomains, ZP-N and ZP-C, separated by a short linker region, that plays an essential role in polymerization of nascent ZP proteins into crosslinked fibrils. Both subdomains adopt immunoglobulin (Ig)-like folds for their 3-dimensional structure. Mouse and human <i>ZP</i> genes are encoded by single-copy genes located on different chromosomes and are highly expressed in the ovary by growing oocytes during late stages of oogenesis. Genes encoding ZP proteins are conserved among mammals, and their expression is regulated by <i>cis</i>-acting sequences located close to the transcription start-site and by the same/similar <i>trans</i>-acting factors. Nascent ZP proteins are synthesized, packaged into vesicles, secreted into the extracellular space, and assembled into long, crosslinked fibrils that have a structural repeat, a ZP2-ZP3 dimer, and constitute the ZP matrix. Fibrils are oriented differently with respect to the oolemma in the inner and outer layers of the ZP. Sequence elements in the ZPD and the carboxy-terminal propeptide of ZP1–4 regulate secretion and assembly of nascent ZP proteins. The presence of both ZP2 and ZP3 is required to assemble ZP fibrils and ZP1 and ZP4 are used to crosslink the fibrils. Inactivation of mouse <i>ZP</i> genes by gene targeting has a detrimental effect on ZP formation around growing oocytes and female fertility. Gene sequence variations in human <i>ZP</i> genes due to point, missense, or frameshift mutations also have a detrimental effect on ZP formation and female fertility. The latter mutations provide additional support for the role of ZPD subdomains and other regions of ZP polypeptide in polymerization of human ZP proteins into fibrils and matrix. |
| first_indexed | 2024-03-10T08:46:55Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T08:46:55Z |
| publishDate | 2021-08-01 |
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| series | Genes |
| spelling | doaj.art-8316ddc7df36432c9b8b450b744805b62023-11-22T07:46:55ZengMDPI AGGenes2073-44252021-08-01128126610.3390/genes12081266Zona Pellucida Genes and Proteins: Essential Players in Mammalian Oogenesis and FertilityPaul M. Wassarman0Eveline S. Litscher1Dept. Cell, Developmental, and Regenerative Biology Icahn School of Medicine at Mount Sinai, Annenberg Building-Box 1020, One Gustave L. Levy Place, New York, NY 10029, USADept. Cell, Developmental, and Regenerative Biology Icahn School of Medicine at Mount Sinai, Annenberg Building-Box 1020, One Gustave L. Levy Place, New York, NY 10029, USAAll mammalian oocytes and eggs are surrounded by a relatively thick extracellular matrix (ECM), the zona pellucida (ZP), that plays vital roles during oogenesis, fertilization, and preimplantation development. Unlike ECM surrounding somatic cells, the ZP is composed of only a few glycosylated proteins, ZP1–4, that are unique to oocytes and eggs. ZP1–4 have a large region of polypeptide, the ZP domain (ZPD), consisting of two subdomains, ZP-N and ZP-C, separated by a short linker region, that plays an essential role in polymerization of nascent ZP proteins into crosslinked fibrils. Both subdomains adopt immunoglobulin (Ig)-like folds for their 3-dimensional structure. Mouse and human <i>ZP</i> genes are encoded by single-copy genes located on different chromosomes and are highly expressed in the ovary by growing oocytes during late stages of oogenesis. Genes encoding ZP proteins are conserved among mammals, and their expression is regulated by <i>cis</i>-acting sequences located close to the transcription start-site and by the same/similar <i>trans</i>-acting factors. Nascent ZP proteins are synthesized, packaged into vesicles, secreted into the extracellular space, and assembled into long, crosslinked fibrils that have a structural repeat, a ZP2-ZP3 dimer, and constitute the ZP matrix. Fibrils are oriented differently with respect to the oolemma in the inner and outer layers of the ZP. Sequence elements in the ZPD and the carboxy-terminal propeptide of ZP1–4 regulate secretion and assembly of nascent ZP proteins. The presence of both ZP2 and ZP3 is required to assemble ZP fibrils and ZP1 and ZP4 are used to crosslink the fibrils. Inactivation of mouse <i>ZP</i> genes by gene targeting has a detrimental effect on ZP formation around growing oocytes and female fertility. Gene sequence variations in human <i>ZP</i> genes due to point, missense, or frameshift mutations also have a detrimental effect on ZP formation and female fertility. The latter mutations provide additional support for the role of ZPD subdomains and other regions of ZP polypeptide in polymerization of human ZP proteins into fibrils and matrix.https://www.mdpi.com/2073-4425/12/8/1266zona pellucidamammalian oogenesisgene expressionproteinszona pellucida domainpolymerization |
| spellingShingle | Paul M. Wassarman Eveline S. Litscher Zona Pellucida Genes and Proteins: Essential Players in Mammalian Oogenesis and Fertility Genes zona pellucida mammalian oogenesis gene expression proteins zona pellucida domain polymerization |
| title | Zona Pellucida Genes and Proteins: Essential Players in Mammalian Oogenesis and Fertility |
| title_full | Zona Pellucida Genes and Proteins: Essential Players in Mammalian Oogenesis and Fertility |
| title_fullStr | Zona Pellucida Genes and Proteins: Essential Players in Mammalian Oogenesis and Fertility |
| title_full_unstemmed | Zona Pellucida Genes and Proteins: Essential Players in Mammalian Oogenesis and Fertility |
| title_short | Zona Pellucida Genes and Proteins: Essential Players in Mammalian Oogenesis and Fertility |
| title_sort | zona pellucida genes and proteins essential players in mammalian oogenesis and fertility |
| topic | zona pellucida mammalian oogenesis gene expression proteins zona pellucida domain polymerization |
| url | https://www.mdpi.com/2073-4425/12/8/1266 |
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