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Keywords = polyspermy block

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21 pages, 859 KB  
Review
Phospholipase Cζ, the Molecular Spark of Fertilization and Male Infertility: Insights from Bench to Bedside
by Aris Kaltsas, Maria-Anna Kyrgiafini, Zissis Mamuris, Fotios Dimitriadis, Athanasios Zachariou, Michael Chrisofos and Nikolaos Sofikitis
Medicina 2025, 61(6), 963; https://doi.org/10.3390/medicina61060963 - 23 May 2025
Cited by 4 | Viewed by 2811
Abstract
Phospholipase C zeta (PLCζ) has emerged as a pivotal sperm-specific factor responsible for triggering oocyte activation, a process essential for successful fertilization and early embryogenesis. A narrative review was conducted to examine the molecular architecture and biochemical features of PLCζ, with particular emphasis [...] Read more.
Phospholipase C zeta (PLCζ) has emerged as a pivotal sperm-specific factor responsible for triggering oocyte activation, a process essential for successful fertilization and early embryogenesis. A narrative review was conducted to examine the molecular architecture and biochemical features of PLCζ, with particular emphasis on how its distinctive structural domains facilitate the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) and the induction of calcium (Ca2+) oscillations in the oocyte. Notably, PLCζ exhibits unique sensitivity to basal Ca2+ levels and the capacity to sustain repetitive intracellular Ca2+ transients that drive meiotic progression and block polyspermy. Clinically, PLCζ deficiency—whether caused by genetic mutations, reduced expression, or improper localization—represents a unifying explanation for certain forms of male infertility, including total fertilization failure (TFF) following intracytoplasmic sperm injection (ICSI). Globozoospermia is a prime example; this condition is characterized by round-headed sperm devoid of acrosomes and exhibiting significantly reduced or absent PLCζ and often results in fertilization failure. Diagnostic methods such as immunofluorescence, Western blotting, and the mouse oocyte-activation test collectively support the identification and characterization of PLCζ-related defects, while genetic testing for mutations in the PLCZ1 gene has proven valuable for identifying hereditary causes of sperm-borne oocyte-activation deficiency (OAD). Therapeutic approaches range from assisted oocyte activation (AOA) with calcium ionophores to emerging interventions that introduce functional PLCζ protein or mRNA directly into the oocyte. These advancements demonstrate the rapid translation of foundational discoveries into clinically actionable interventions. Future investigations are poised to refine diagnostic assays, standardize measurement protocols, and explore the potential of gene therapy or CRISPR/Cas9-mediated correction for heritable PLCζ abnormalities. By addressing both the molecular basis and translational applications of PLCζ, recent findings underscore its indispensable role in fertility care and lay out a path toward further innovation in assisted reproductive technologies. Full article
(This article belongs to the Special Issue From Conception to Birth: Embryonic Development and Disease)
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24 pages, 1393 KB  
Review
The Role of Female and Male Genes in Regulating Pollen Tube Guidance in Flowering Plants
by Siyuan Zheng, Feng Wang, Zehui Liu, Hongbin Zhang, Liangsheng Zhang and Dan Chen
Genes 2024, 15(11), 1367; https://doi.org/10.3390/genes15111367 - 24 Oct 2024
Cited by 5 | Viewed by 5198
Abstract
In flowering plants, fertilization is a complex process governed by precise communication between the male and female gametophytes. This review focuses on the roles of various female gametophyte cells—synergid, central, and egg cells—in facilitating pollen tube guidance and ensuring successful fertilization. Synergid cells [...] Read more.
In flowering plants, fertilization is a complex process governed by precise communication between the male and female gametophytes. This review focuses on the roles of various female gametophyte cells—synergid, central, and egg cells—in facilitating pollen tube guidance and ensuring successful fertilization. Synergid cells play a crucial role in attracting the pollen tube, while the central cell influences the direction of pollen tube growth, and the egg cell is responsible for preventing polyspermy, ensuring correct fertilization. The review also examines the role of the pollen tube in this communication, highlighting the mechanisms involved in its growth regulation, including the importance of pollen tube receptors, signal transduction pathways, cell wall dynamics, and ion homeostasis. The Ca2+ concentration gradient is identified as a key factor in guiding pollen tube growth toward the ovule. Moreover, the review briefly compares these communication processes in angiosperms with those in non-flowering plants, such as mosses, ferns, and early gymnosperms, providing evolutionary insights into gametophytic signaling. Overall, this review synthesizes the current understanding of male–female gametophyte interactions and outlines future directions for research in plant reproductive biology. Full article
(This article belongs to the Special Issue Genetics and Genomics in Horticultural Plants)
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13 pages, 3935 KB  
Article
Tannin Reduces the Incidence of Polyspermic Penetration in Porcine Oocytes
by Jing-Tao Sun, Jia-Hui Liu, Xi-Qing Jiang, Xin Luo, Jin-Dong Yuan, Qi Zhang, Xin-Yue Qi, Sanghoon Lee, Zhong-Hua Liu and Jun-Xue Jin
Antioxidants 2022, 11(10), 2027; https://doi.org/10.3390/antiox11102027 - 14 Oct 2022
Cited by 7 | Viewed by 3135
Abstract
Tannin (TA) improves porcine oocyte cytoplasmic maturation and subsequent embryonic development after in vitro fertilization (IVF). However, the mechanism through which TA blocks polyspermy after IVF remains unclear. Hence, the biological function of organelles (cortical granule [CG], Golgi apparatus, endoplasmic reticulum [ER], and [...] Read more.
Tannin (TA) improves porcine oocyte cytoplasmic maturation and subsequent embryonic development after in vitro fertilization (IVF). However, the mechanism through which TA blocks polyspermy after IVF remains unclear. Hence, the biological function of organelles (cortical granule [CG], Golgi apparatus, endoplasmic reticulum [ER], and mitochondria) and the incidence of polyspermic penetration were examined. We found no significant difference in oocyte nuclear maturation among the 1 µg/mL, 10 µg/mL TA, and control groups. Moreover, 100 μg/mL TA significantly reduced 1st polar body formation rate compared to the other groups. Additionally, 1 and 10 μg/mL TA significantly increased the protein levels of GDF9, BMP15, and CDK1 compared to the control and 100 μg/mL TA groups. Interestingly, 1 and 10 μg/mL TA improved the normal distribution of CGs, Golgi, ER, and mitochondria by upregulating organelle-related gene expression and downregulating ER stress (CHOP) gene expression. Simultaneously, 1 and 10 μg/mL TA significantly increased the proportion of normal fertilized oocytes (2 pronuclei; 2 PN) and blastocyst formation rate compared to the control, as well as that of 100 μg/mL TA after IVF by upregulating polyspermy-related genes. In conclusion, TA during IVM enhances 2PN and blastocyst formation rates by regulating organelles’ functions and activities. Full article
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21 pages, 9221 KB  
Article
Effects of Dithiothreitol on Fertilization and Early Development in Sea Urchin
by Nunzia Limatola, Jong Tai Chun, Sawsen Cherraben, Jean-Louis Schmitt, Jean-Marie Lehn and Luigia Santella
Cells 2021, 10(12), 3573; https://doi.org/10.3390/cells10123573 - 17 Dec 2021
Cited by 9 | Viewed by 4402
Abstract
The vitelline layer (VL) of a sea urchin egg is an intricate meshwork of glycoproteins that intimately ensheathes the plasma membrane. During fertilization, the VL plays important roles. Firstly, the receptors for sperm reside on the VL. Secondly, following cortical granule exocytosis, the [...] Read more.
The vitelline layer (VL) of a sea urchin egg is an intricate meshwork of glycoproteins that intimately ensheathes the plasma membrane. During fertilization, the VL plays important roles. Firstly, the receptors for sperm reside on the VL. Secondly, following cortical granule exocytosis, the VL is elevated and transformed into the fertilization envelope (FE), owing to the assembly and crosslinking of the extruded materials. As these two crucial stages involve the VL, its alteration was expected to affect the fertilization process. In the present study, we addressed this question by mildly treating the eggs with a reducing agent, dithiothreitol (DTT). A brief pretreatment with DTT resulted in partial disruption of the VL, as judged by electron microscopy and by a novel fluorescent polyamine probe that selectively labelled the VL. The DTT-pretreated eggs did not elevate the FE but were mostly monospermic at fertilization. These eggs also manifested certain anomalies at fertilization: (i) compromised Ca2+ signaling, (ii) blocked translocation of cortical actin filaments, and (iii) impaired cleavage. Some of these phenotypic changes were reversed by restoring the DTT-exposed eggs in normal seawater prior to fertilization. Our findings suggest that the FE is not the decisive factor preventing polyspermy and that the integrity of the VL is nonetheless crucial to the egg’s fertilization response. Full article
(This article belongs to the Special Issue 10th Anniversary of Cells—Advances in Cell Cycle)
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13 pages, 1502 KB  
Article
Suppression of Non-Random Fertilization by MHC Class I Antigens
by Junki Kamiya, Woojin Kang, Keiichi Yoshida, Ryota Takagi, Seiya Kanai, Maito Hanai, Akihiro Nakamura, Mitsutoshi Yamada, Yoshitaka Miyamoto, Mami Miyado, Yoko Kuroki, Yoshiki Hayashi, Akihiro Umezawa, Natsuko Kawano and Kenji Miyado
Int. J. Mol. Sci. 2020, 21(22), 8731; https://doi.org/10.3390/ijms21228731 - 19 Nov 2020
Cited by 3 | Viewed by 8325
Abstract
Hermaphroditic invertebrates and plants have a self-recognition system on the cell surface of sperm and eggs, which prevents their self-fusion and enhances non-self-fusion, thereby contributing to genetic variation. However, the system of sperm–egg recognition in mammals is under debate. To address this issue, [...] Read more.
Hermaphroditic invertebrates and plants have a self-recognition system on the cell surface of sperm and eggs, which prevents their self-fusion and enhances non-self-fusion, thereby contributing to genetic variation. However, the system of sperm–egg recognition in mammals is under debate. To address this issue, we explored the role of major histocompatibility complex class I (MHC class I, also known as histocompatibility 2-Kb or H2-Kb and H2-Db in mice) antigens by analyzing H2-Kb-/-H2-Db-/-β2-microglobulin (β2M)-/- triple-knockout (T-KO) male mice with full fertility. T-KO sperm exhibited an increased sperm number in the perivitelline space of wild-type (WT) eggs in vitro. Moreover, T-KO sperm showed multiple fusion with zona pellucida (ZP)-free WT eggs, implying that the ability of polyspermy block for sperm from T-KO males was weakened in WT eggs. When T-KO male mice were intercrossed with WT female mice, the percentage of females in progeny increased. We speculate that WT eggs prefer fusion with T-KO sperm, more specifically X-chromosome-bearing sperm (X sperm), suggesting the presence of preferential (non-random) fertilization in mammals, including humans. Full article
(This article belongs to the Special Issue Molecular Biology of Spermatozoa 2.0)
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16 pages, 2783 KB  
Article
Sperm Cohort-Specific Zinc Signature Acquisition and Capacitation-Induced Zinc Flux Regulate Sperm-Oviduct and Sperm-Zona Pellucida Interactions
by Karl Kerns, Momal Sharif, Michal Zigo, Wei Xu, Lauren E. Hamilton, Miriam Sutovsky, Mark Ellersieck, Erma Z. Drobnis, Nicolai Bovin, Richard Oko, David Miller and Peter Sutovsky
Int. J. Mol. Sci. 2020, 21(6), 2121; https://doi.org/10.3390/ijms21062121 - 19 Mar 2020
Cited by 41 | Viewed by 6679
Abstract
Building on our recent discovery of the zinc signature phenomenon present in boar, bull, and human spermatozoa, we have further characterized the role of zinc ions in the spermatozoa’s pathway to fertilization. In boar, the zinc signature differed between the three major boar [...] Read more.
Building on our recent discovery of the zinc signature phenomenon present in boar, bull, and human spermatozoa, we have further characterized the role of zinc ions in the spermatozoa’s pathway to fertilization. In boar, the zinc signature differed between the three major boar ejaculate fractions, the initial pre-rich, the sperm-rich, and the post-sperm-rich fraction. These differences set in the sperm ejaculatory sequence establish two major sperm cohorts with marked differences in their sperm capacitation progress. On the subcellular level, we show that the capacitation-induced Zn-ion efflux allows for sperm release from oviductal glycans as analyzed with the oviductal epithelium mimicking glycan binding assay. Sperm zinc efflux also activates zinc-containing enzymes and proteases involved in sperm penetration of the zona pellucida, such as the inner acrosomal membrane matrix metalloproteinase 2 (MMP2). Both MMP2 and the 26S proteasome showed severely reduced activity in the presence of zinc ions, through studies using by gel zymography and the fluorogenic substrates, respectively. In the context of the fertilization-induced oocyte zinc spark and the ensuing oocyte-issued polyspermy-blocking zinc shield, the inhibitory effect of zinc on sperm-borne enzymes may contribute to the fast block of polyspermy. Altogether, our findings establish a new paradigm on the role of zinc ions in sperm function and pave the way for the optimization of animal semen analysis, artificial insemination (AI), and human male-factor infertility diagnostics. Full article
(This article belongs to the Special Issue Advances in Molecular Regulation of Spermatozoa Function)
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