CD147 deficiency is associated with impairedsperm motility/acrosome reaction and offersa therapeutic target for asthenozoospermia

Patients with asthenozoospermia often present multiple defects in sperm functions apart from a decrease in sperm motility. However, the etiological factors underlying these multifaceted defects remain mostly unexplored, which may lead to unnecessary treatment and unsatisfactory assisted reproductive technologies (ART) outcome. Here, we show that the protein levels of CD147 were lowered in sperm obtained from asthenozoospermic infertile patients exhibiting defects in both sperm motility and the acrosome reaction. Whereas CD147 maintained sperm motility before capacitation, female tract-derived soluble CD147 interacted with sperm-bound CD147 to induce an acrosome reaction in capacitated sperm. Soluble CD147 treatment restored the acrosome reaction and improved the fertility of sperm from patients with asthenozoospermia. Mechanistically, CD147 promotes sperm motility and acrosome reaction (AR) by eliciting Ca2+ influx through soluble CD147 binding to sperm-bound CD147. Notably, the level of soluble CD147 in seminal plasma was positively correlated with the fertilization rate and pregnancy outcome in infertile couples undergoing in vitro fertilization. Our study has identified a marker for the diagnosis and a therapeutic target for the defective AR capability in asthenozoospermia and a candidate for the prediction of in vitro fertilization outcomes for male infertile patients that facilitates the development of precision medicine in ART.

• Publication year

  2021

• Venue

  Molecular Therapy: Nucleic Acids

• Publication date

  2021-11-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.1016/j.omtn.2021.11.009PMID 34900396PMCID 8626663
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2020cited by this paper
• Viable acrosome-intact human spermatozoa in the ejaculate as a marker of semen quality and fertility status

  2018cited by this paper
• CD147 Induces Epithelial-to-Mesenchymal Transition by Disassembling Cellular Apoptosis Susceptibility Protein/E-Cadherin/β-Catenin Complex in Human Endometriosis.

  2018cited by this paper
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  2018cited by this paper
• Acrosome reaction and chromatin integrity as additional parameters of semen analysis to predict fertilization and blastocyst rates

  2018cited by this paper
• CD147 regulates extrinsic apoptosis in spermatocytes by modulating NFκB signaling pathways

  2016cited by this paper
• Regulation and roles of Ca2+ stores in human sperm

  2015influential reference
• 'How to count sperm properly': checklist for acceptability of studies based on human semen analysis.

  2015influential reference
• CD147 (EMMPRIN/Basigin) in kidney diseases: from an inflammation and immune system viewpoint.

  2015cited by this paper
• Deficient human β-defensin 1 underlies male infertility associated with poor sperm motility and genital tract infection

  2014cited by this paper
• Full-length soluble CD147 promotes MMP-2 expression and is a potential serological marker in detection of hepatocellular carcinoma

  2014cited by this paper
• Assessment of sperm hyperactivated motility and acrosome reaction can discriminate the use of spermatozoa for conventional in vitro fertilisation or intracytoplasmic sperm injection: Preliminary results

  2014cited by this paper
• Pathogenic Neisseria meningitidis utilizes CD147 for vascular colonization

  2014influential reference
• Novel regulators of spermatogenesis.

  2014cited by this paper
• Basigin null mutant male mice are sterile and exhibit impaired interactions between germ cells and Sertoli cells.

  2013cited by this paper
• The cell biology of mammalian fertilization

  2013cited by this paper
• Sperm morphology assessment using strict (tygerberg) criteria.

  2013cited by this paper
• CD147 regulates apoptosis in mouse spermatocytes but not spermatogonia.

  2012cited by this paper
• Interactions among HCLS1, HAX1 and LEF-1 proteins are essential for G-CSF–triggered granulopoiesis

  2012cited by this paper
• Mechanism of sperm capacitation and the acrosome reaction: role of protein kinases.

  2012cited by this paper
• New insights into germ cell migration and survival/apoptosis in spermatogenesis

  2012cited by this paper
• Dimerization is essential for HAb18G/CD147 promoting tumor invasion via MAPK pathway.

  2012cited by this paper
• Basigin/CD147 promotes renal fibrosis after unilateral ureteral obstruction.

  2011cited by this paper
• CD147 is required for matrix metalloproteinases-2 production and germ cell migration during spermatogenesis.

  2011cited by this paper
• Acrosome reaction in the cumulus oophorus revisited: involvement of a novel sperm-released factor NYD-SP8

  2011influential reference
• Most fertilizing mouse spermatozoa begin their acrosome reaction before contact with the zona pellucida during in vitro fertilization

  2011cited by this paper
• Calcium channels in the development, maturation, and function of spermatozoa.

  2011influential reference
• The Annulus of the Mouse Sperm Tail Is Required to Establish a Membrane Diffusion Barrier That Is Engaged During the Late Steps of Spermiogenesis1

  2010cited by this paper
• Hyaluronan binding assay (HBA) vs. sperm penetration assay (SPA): Can HBA replace the SPA test in male partner screening before in vitro fertilization?

  2010cited by this paper
• The human oocyte and cumulus cells relationship: new insights from the cumulus cell transcriptome.

  2010cited by this paper
• A sperm GPI-anchored protein elicits sperm-cumulus cross-talk leading to the acrosome reaction

  2009cited by this paper
• Production of offspring from a germline stem cell line derived from neonatal ovaries

  2009cited by this paper
• Removal of acrosomal membrane from sperm head improves development of rat zygotes derived from intracytoplasmic sperm injection.

  2009cited by this paper
• Basigin-2 Is a Cell Surface Receptor for Soluble Basigin Ligand*

  2008cited by this paper
• Molecular Biology of the Cell 4th edition

  2007cited by this paper
• Simultaneous removal of sperm plasma membrane and acrosome before intracytoplasmic sperm injection improves oocyte activation/embryonic development

  2006cited by this paper
• Direct observation of individual endogenous protein complexes in situ by proximity ligation

  2006cited by this paper
• Incorporation of the acrosome into the oocyte during intracytoplasmic sperm injection could be potentially hazardous to embryo development.

  2005cited by this paper
• Treatment of male infertility.

  2005cited by this paper
• Mammalian fertilization.

  2004cited by this paper
• HAb18G/CD147-mediated calcium mobilization and hepatoma metastasis require both C-terminal and N-terminal domains

  2004cited by this paper
• Molecular Modifications of MC31/CE9, a Sperm Surface Molecule, During Sperm Capacitation and the Acrosome Reaction in the Rat: Is MC31/CE9 Required for Fertilization?1

  2004cited by this paper
• ASTHENOZOOSPERMIA: ANALYSIS OF A LARGE POPULATION

  2003cited by this paper
• The significance of the ionophore-challenged acrosome reaction in the prediction of successful outcome of controlled ovarian stimulation and intrauterine insemination.

  2003cited by this paper
• Full-Term Development of Golden Hamster Oocytes Following Intracytoplasmic Sperm Head Injection

  2002cited by this paper
• Behaviour of a sperm surface transmembrane glycoprotein basigin during epididymal maturation and its role in fertilization in mice.

  2002cited by this paper
• Establishment and characterization of a steroidogenic human granulosa-like tumor cell line, KGN, that expresses functional follicle-stimulating hormone receptor.

  2001cited by this paper
• A profile of fertilization in mammals

  2001cited by this paper
• The Involvement of HAb18G/CD147 in Regulation of Store-operated Calcium Entry and Metastasis of Human Hepatoma Cells*

  2001cited by this paper
• Effects of progesterone on sperm function: mechanisms of action.

  2000cited by this paper
• Printed in U.S.A. Copyright © 2001 by The Endocrine Society

  2000cited by this paper
• CASA--practical aspects.

  2000cited by this paper
• Female sterility in mice lacking the basigin gene, which encodes a transmembrane glycoprotein belonging to the immunoglobulin superfamily

  1998cited by this paper
• Outcome of intracytoplasmic sperm injection with testicular spermatozoa in obstructive and non-obstructive azoospermia.

  1996cited by this paper
• Intrauterine insemination: evaluation of the results according to the woman's age, sperm quality, total sperm count per insemination and life table analysis.

  1996cited by this paper
• Pregnancies after testicular sperm extraction and intracytoplasmic sperm injection in non-obstructive azoospermia.

  1995cited by this paper
• Recombinant human zona pellucida protein ZP3 produced by chinese hamster ovary cells induces the human sperm acrosome reaction and promotes sperm-egg fusion.

  1994cited by this paper
• Treatment of male infertility

  1994cited by this paper
• Ca(2+)-independent induction of acrosome reaction by protein kinase C in human sperm.

  1992cited by this paper
• Spontaneous and ionophore induced acrosome reaction in asthenozoospermic infertile semen.

  1992cited by this paper
• Human sperm capacitation and the acrosome reaction.

  1991influential reference
• The human sperm-hamster egg penetration assay: prognostic value.

  1988cited by this paper
• Induction of acrosome reactions by the human zona pellucida.

  1988cited by this paper
• O-linked oligosaccharides of mouse egg ZP3 account for its sperm receptor activity

  1985cited by this paper
• Mouse gamete interactions: the zona pellucida is the site of the acrosome reaction leading to fertilization in vitro.

  1982cited by this paper

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  2025cites this paper
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  2025cites this paper
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  2024cites this paper
• CD147 mediates S protein pseudovirus of SARS-CoV-2 infection and its induction of spermatogonia apoptosis

  2024cites this paper
• A systematic review identifying seminal plasma biomarkers and their predictive ability on IVF and ICSI outcomes.

  2023cites this paper
• SARS-CoV-2 and male infertility: from short- to long-term impacts

  2023cites this paper
• Spatial Distribution of SARS-CoV-2 Receptors and Proteases in Testicular Cells

  2023cites this paper
• Coiled-coil domain-containing 38 is required for acrosome biogenesis and fibrous sheath assembly in mice.

  2023cites this paper
• The microbiome and male infertility: looking into the past to move forward

  2022cites this paper
• CD147 and MMPs as key factors in physiological and pathological processes.

  2022cites this paper