-
ELife Jan 2022Fertility in female mammals, including mice and humans, is dependent on the presence of a zona pellucida (ZP) around growing oocytes and unfertilized eggs. A ZP is... (Review)
Review
Fertility in female mammals, including mice and humans, is dependent on the presence of a zona pellucida (ZP) around growing oocytes and unfertilized eggs. A ZP is required to stabilize contacts between oocyte microvilli and follicle cell projections that traverse the ZP to form gap junctions that support the health of growing oocytes and developing follicles. In the absence of a ZP, due to inactivation or mutation of genes encoding ZP proteins, there is a loss of contacts between growing oocytes and neighboring follicle cells and a concomitant reduction in the production of ovulated eggs that results in female infertility.
Topics: Animals; Female; Humans; Infertility, Female; Mammals; Mice; Oocytes; Oogenesis; Zona Pellucida
PubMed: 35076396
DOI: 10.7554/eLife.76106 -
Genes Aug 2021All mammalian oocytes and eggs are surrounded by a relatively thick extracellular matrix (ECM), the zona pellucida (ZP), that plays vital roles during oogenesis,... (Review)
Review
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 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 -acting sequences located close to the transcription start-site and by the same/similar -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 genes by gene targeting has a detrimental effect on ZP formation around growing oocytes and female fertility. Gene sequence variations in human 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.
Topics: Animals; Female; Fertility; Humans; Mammals; Mice; Oocytes; Oogenesis; Zona Pellucida
PubMed: 34440440
DOI: 10.3390/genes12081266 -
The Journal of Biological Chemistry Sep 2008All mammalian eggs are surrounded by a relatively thick extracellular coat, the zona pellucida, that plays vital roles during oogenesis, fertilization, and... (Review)
Review
All mammalian eggs are surrounded by a relatively thick extracellular coat, the zona pellucida, that plays vital roles during oogenesis, fertilization, and preimplantation development. The mouse zona pellucida consists of three glycoproteins that are synthesized solely by growing oocytes and assemble into long fibrils that constitute a matrix. Zona pellucida glycoproteins are responsible for species-restricted binding of sperm to unfertilized eggs, inducing sperm to undergo acrosomal exocytosis, and preventing sperm from binding to fertilized eggs. Many features of mammalian and non-mammalian egg coat polypeptides have been conserved during several hundred million years of evolution.
Topics: Acrosome; Animals; Biological Evolution; Embryo Implantation; Exocytosis; Female; Fertilization; Glycoproteins; Humans; Male; Mice; Oocytes; Oogenesis; Zona Pellucida
PubMed: 18539589
DOI: 10.1074/jbc.R800027200 -
Biomolecules Jun 2017Amyloids are traditionally considered pathological protein aggregates that play causative roles in neurodegenerative disease, diabetes and prionopathies. However,... (Review)
Review
Amyloids are traditionally considered pathological protein aggregates that play causative roles in neurodegenerative disease, diabetes and prionopathies. However, increasing evidence indicates that in many biological systems nonpathological amyloids are formed for functional purposes. In this review, we will specifically describe amyloids that carry out biological roles in sexual reproduction including the processes of gametogenesis, germline specification, sperm maturation and fertilization. Several of these functional amyloids are evolutionarily conserved across several taxa, including human, emphasizing the critical role amyloids perform in reproduction. Evidence will also be presented suggesting that, if altered, some functional amyloids may become pathological.
Topics: Amyloid; Animals; Female; Fertilization; Gametogenesis; Humans; Male; Reproduction; Spermatozoa; Zona Pellucida
PubMed: 28661450
DOI: 10.3390/biom7030046 -
Cells Jan 2021Sperm-zona pellucida (ZP) interaction, involving the binding of sperm surface ligands to complementary carbohydrates of ZP, is the first direct gamete contact event... (Review)
Review
Sperm-zona pellucida (ZP) interaction, involving the binding of sperm surface ligands to complementary carbohydrates of ZP, is the first direct gamete contact event crucial for subsequent gamete fusion and successful fertilization in mammals. It is a complex process mediated by the coordinated engagement of multiple ZP receptors forming high-molecular-weight (HMW) protein complexes at the acrosomal region of the sperm surface. The present article aims to review the current understanding of sperm-ZP binding in the four most studied mammalian models, i.e., murine, porcine, bovine, and human, and summarizes the candidate ZP receptors with established ZP affinity, including their origins and the mechanisms of ZP binding. Further, it compares and contrasts the ZP structure and carbohydrate composition in the aforementioned model organisms. The comprehensive understanding of sperm-ZP interaction mechanisms is critical for the diagnosis of infertility and thus becomes an integral part of assisted reproductive therapies/technologies.
Topics: Animals; Cell Communication; Humans; Ligands; Male; Mammals; Membrane Glycoproteins; Receptors, Cell Surface; Spermatozoa; Zona Pellucida
PubMed: 33445482
DOI: 10.3390/cells10010133 -
Reproduction & Fertility Jul 2021Sperm DNA fragmentation (SDF) and sperm morphological defects can negatively affect ART outcomes. Consequently, there is a need for additional semen processing technique...
UNLABELLED
Sperm DNA fragmentation (SDF) and sperm morphological defects can negatively affect ART outcomes. Consequently, there is a need for additional semen processing technique that accounts for sperm DNA status and morphology prior to ICSI. The objective was to evaluate the efficacy of an additional zona pellucida adhesion-based sperm selection for obtaining sperm populations with a high percentage of normal morphology and DNA integrity as compared to native semen and routine swim-up preparation. Semen samples from 78 normozoospermic men were subjected to swim up and placed in petri dishes coated with 48 acid-solubilized zonae pellucidae. Sperm DNA fragmentation and morphology were assessed in the native semen, the swim-up samples, and the zona-adhered spermatozoa from each patient. The mean sperm DNA fragmentation of the zona-selected spermatozoa (3.5 ± 0.7%) was significantly lower than the swim-up samples (15.3 ± 5.2%) ( < 0.001) and native semen (24.9 ± 7.1%) ( < 0.001). All of the samples had lower levels of DNA damage after additional selection by zona pellucida adhesion. Significantly higher percentage of sperm with normal morphology was observed after zona-adhesion selection (11.4 ± 3.9%) when compared to the swim-up samples (8.9 ± 4.3%) ( < 0.001) or the native semen (5.3 ± 3.2%) ( < 0.001). In 94% of the samples, the percentage of spermatozoa with normal morphology increased after the additional zona selection. This study demonstrates that sperm selection by additional zona-adhesion technique yields a significantly higher percentage of spermatozoa with normal morphology as well as a significantly decreased level of DNA fragmentation when compared to the native semen and the swim-up-only prepared samples.
LAY SUMMARY
High level of DNA folding known as sperm DNA fragmentation (SDF) inside each sperm and defects in the shape, size, and structure of the sperm can negatively affect assisted reproduction treatment (ART) outcomes. Consequently, there is a need for additional semen processing techniques that account for sperm quality prior to ART. Our team designed a simple technique using proteins from the coat around the egg (zona pellucida) to enhance sperm selection procedures based on natural sperm-egg interactions. Using this technique in combination with the most common techniques used in ART yields a significantly higher percentage of sperm with normal shape, size, and structure and a decreased level of DNA fragmentation. This sperm zona-selection technique would be beneficial if introduced in the ART practice to yield sperm with higher fertilization potential.
Topics: DNA Fragmentation; Humans; Male; Semen; Sperm-Ovum Interactions; Spermatozoa; Zona Pellucida
PubMed: 35118392
DOI: 10.1530/RAF-21-0041 -
Current Topics in Developmental Biology 2018All animal oocytes are surrounded by a glycoproteinaceous egg coat, a specialized extracellular matrix that serves both structural and species-specific roles during... (Review)
Review
All animal oocytes are surrounded by a glycoproteinaceous egg coat, a specialized extracellular matrix that serves both structural and species-specific roles during fertilization. Egg coat glycoproteins polymerize into the extracellular matrix of the egg coat using a conserved protein-protein interaction module-the zona pellucida (ZP) domain-common to both vertebrates and invertebrates, suggesting that the basic structural features of egg coats have been conserved across hundreds of millions of years of evolution. Egg coat proteins, as with other proteins involved in reproduction, are frequently found to be rapidly evolving. Given that gamete compatibility must be maintained for the fitness of sexually reproducing organisms, this finding is somewhat paradoxical and suggests a role for adaptive diversification in reproductive protein evolution. Here we review the structure and function of metazoan egg coat proteins, with an emphasis on the potential role their evolution has played in the creation and maintenance of species boundaries.
Topics: Animals; Biological Evolution; Egg Proteins; Female; Humans; Invertebrates; Protein Domains; Protein Multimerization; Vertebrates; Zona Pellucida; Zona Pellucida Glycoproteins
PubMed: 29853187
DOI: 10.1016/bs.ctdb.2018.03.005 -
International Journal of Molecular... Mar 2021Mammalian oocytes are surrounded by an extracellular coat called the zona pellucida (ZP), which, from an evolutionary point of view, is the most ancient of the coats... (Review)
Review
Mammalian oocytes are surrounded by an extracellular coat called the zona pellucida (ZP), which, from an evolutionary point of view, is the most ancient of the coats that envelope vertebrate oocytes and conceptuses. This matrix separates the oocyte from cumulus cells and is responsible for species-specific recognition between gametes, preventing polyspermy and protecting the preimplantation embryo. The ZP is a dynamic structure that shows different properties before and after fertilization. Until very recently, mammalian ZP was believed to be composed of only three glycoproteins, ZP1, ZP2 and ZP3, as first described in mouse. However, studies have revealed that this composition is not necessarily applicable to other mammals. Such differences can be explained by an analysis of the molecular evolution of the ZP gene family, during which ZP genes have suffered pseudogenization and duplication events that have resulted in differing models of ZP protein composition. The many discoveries made in recent years related to ZP composition and evolution suggest that a compilation would be useful. Moreover, this review analyses ZP biosynthesis, the role of each ZP protein in different mammalian species and how these proteins may interact among themselves and with other proteins present in the oviductal lumen.
Topics: Animals; Biomarkers; Cell Communication; Evolution, Molecular; Female; Gene Expression Regulation, Developmental; Male; Mammals; Oocytes; Ovum; Protein Transport; Spermatozoa; Zona Pellucida; Zona Pellucida Glycoproteins
PubMed: 33806989
DOI: 10.3390/ijms22063276 -
Biomechanics and Modeling in... Apr 2021Probing mechanical properties of cells has been identified as a means to infer information on their current state, e.g. with respect to diseases or differentiation....
Probing mechanical properties of cells has been identified as a means to infer information on their current state, e.g. with respect to diseases or differentiation. Oocytes have gained particular interest, since mechanical parameters are considered potential indicators of the success of in vitro fertilisation procedures. Established tests provide the structural response of the oocyte resulting from the material properties of the cell's components and their disposition. Based on dedicated experiments and numerical simulations, we here provide novel insights on the origin of this response. In particular, polarised light microscopy is used to characterise the anisotropy of the zona pellucida, the outermost layer of the oocyte composed of glycoproteins. This information is combined with data on volumetric changes and the force measured in relaxation/cyclic, compression/indentation experiments to calibrate a multi-phasic hyper-viscoelastic model through inverse finite element analysis. These simulations capture the oocyte's overall force response, the distinct volume changes observed in the zona pellucida, and the structural alterations interpreted as a realignment of the glycoproteins with applied load. The analysis reveals the presence of two distinct timescales, roughly separated by three orders of magnitude, and associated with a rapid outflow of fluid across the external boundaries and a long-term, progressive relaxation of the glycoproteins, respectively. The new results allow breaking the overall response down into the contributions from fluid transport and the mechanical properties of the zona pellucida and ooplasm. In addition to the gain in fundamental knowledge, the outcome of this study may therefore serve an improved interpretation of the data obtained with current methods for mechanical oocyte characterisation.
Topics: Animals; Anisotropy; Biomechanical Phenomena; Cumulus Cells; Elasticity; Finite Element Analysis; Oocytes; Swine; Viscosity; Zona Pellucida
PubMed: 33533999
DOI: 10.1007/s10237-020-01414-4 -
Biology of Reproduction Nov 2022The zona pellucida plays a crucial role in the process of fertilization to early embryonic development, including cellular arrangement and communication between...
The zona pellucida plays a crucial role in the process of fertilization to early embryonic development, including cellular arrangement and communication between blastomeres. However, little is known regarding the role of the zona pellucida in pre- and post-implantation embryonic development associated with gene expression. We investigated the effect of zona pellucida removal on pre- and post-implantation development of mouse embryos. After zona pellucida removal of two-cell stage embryos was performed by acid Tyrode's solution, which is commonly used for zona pellucida treatment, compaction occurred earlier in zona pellucida-free than zona pellucida-intact embryos. In addition, the expression of differentiation-related genes in the inner cell mass and trophectoderm was significantly altered in zona pellucida-free blastocyst compared with zona pellucida-intact embryos. After embryo transfer, the rate of implantation and live fetuses was lower in zona pellucida-free embryos than in control embryos, whereas the fetal weight at E17.5 was not different. However, placental weight significantly increased in zona pellucida-free embryos. RNA-sequencing analysis of the placenta showed that a total of 473 differentially expressed genes significantly influenced the biological process. The present study suggests that zona pellucida removal by acid Tyrode's solution at the two-cell stage not only disturbs the expression pattern of inner cell mass-/trophectoderm-related genes but affects the post-implantation development of mouse embryos. Overall, this study provides deeper insight into the role of the zona pellucida during early embryonic development and the viability of post-implantation development.
Topics: Female; Mice; Pregnancy; Animals; Placenta; Zona Pellucida; Blastocyst; Embryonic Development; Gene Expression
PubMed: 35948000
DOI: 10.1093/biolre/ioac155