Dataset Information

Spermatogenic cell-specific SPACA4 is essential for efficient sperm-zona pellucida binding in vitro.

ABSTRACT: Fertilization is a complex and highly regulated process that involves a series of molecular interactions between sperm and oocytes. However, the mechanisms of proteins involved in human fertilization, such as that of testis-specific SPACA4, remain poorly understood. Here we demonstrated that SPACA4 is a spermatogenic cell-specific protein. SPACA4 is expressed during spermatogenesis, upregulated in early-stage spermatids, and downregulated in elongating spermatids. SPACA4 is an intracellular protein that locates in the acrosome and is lost during the acrosome reaction. Incubation with antibodies against SPACA4 inhibited the binding of spermatozoa to zona pellucida. SPACA4 protein expression levels across different semen parameters were similar but varied significantly among patients. A prospective clinical study found no association between SPACA4 protein levels and fertilization or cleavage rates. Thus, the study suggests a novel function for SPACA4 in human fertilization in a non-dose-dependent manner. However, a larger clinical trial is required to evaluate the potential use of sperm SPACA4 protein levels to predict fertilization potential.

SUBMITTER: Chen L

PROVIDER: S-EPMC10291262 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Spermatogenic cell-specific SPACA4 is essential for efficient sperm-zona pellucida binding <i>in vitro</i>.

Chen Lin L Song Junli J Zhang Jinglei J Luo Zicong Z Chen Xuren X Zhou Canquan C Shen Xiaoting X

Frontiers in cell and developmental biology 20230612

Fertilization is a complex and highly regulated process that involves a series of molecular interactions between sperm and oocytes. However, the mechanisms of proteins involved in human fertilization, such as that of testis-specific SPACA4, remain poorly understood. Here we demonstrated that SPACA4 is a spermatogenic cell-specific protein. SPACA4 is expressed during spermatogenesis, upregulated in early-stage spermatids, and downregulated in elongating spermatids. SPACA4 is an intracellular prot ...[more]

PMID: 37377732

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Project description:Despite decades of research, the mechanism by which the fertilizing spermatozoon penetrates the mammalian vitelline membrane, the zona pellucida (ZP) remains one of the unexplained fundamental events of human/mammalian development. Evidence has been accumulating in support of the 26S proteasome as a candidate for echinoderm, ascidian and mammalian egg coat lysin. Monitoring ZP protein degradation by sperm during fertilization is nearly impossible because those few spermatozoa that penetrate the ZP leave behind a virtually untraceable residue of degraded proteins. We have overcome this hurdle by designing an experimentally consistent in vitro system in which live boar spermatozoa are co-incubated with ZP-proteins (ZPP) solubilized from porcine oocytes. Using this assay, mimicking sperm-egg interactions, we demonstrate that the sperm-borne proteasomes can degrade the sperm receptor protein ZPC. Upon coincubation with motile spermatozoa, the solubilized ZPP, which appear to be ubiquitinated, adhered to sperm acrosomal caps and induced acrosomal exocytosis/formation of the acrosomal shroud. The degradation of the sperm receptor protein ZPC was assessed by Western blotting band-densitometry and proteomics. A nearly identical pattern of sperm receptor degradation, evident already within the first 5 min of coincubation, was observed when the spermatozoa were replaced with the isolated, enzymatically active, sperm-derived proteasomes. ZPC degradation was blocked by proteasomal inhibitors and accelerated by ubiquitin-aldehyde(UBAL), a modified ubiquitin protein that stimulates proteasomal proteolysis. Such a degradation pattern of ZPC is consistent with in vitro fertilization studies, in which proteasomal inhibitors completely blocked fertilization, and UBAL increased fertilization and polyspermy rates. Preincubation of intact zona-enclosed ova with isolated active sperm proteasomes caused digestion, abrasions and loosening of the exposed zonae, and significantly reduced the fertilization/polyspermy rates after IVF, accompanied by en-mass detachment of zona bound sperm. Thus, the sperm borne 26S proteasome is a candidate zona lysin in mammals. This new paradigm has implications for contraception and assisted reproductive technologies in humans, as well as animals.

Dataset Information

Spermatogenic cell-specific SPACA4 is essential for efficient sperm-zona pellucida binding in vitro.

Publications

Spermatogenic cell-specific SPACA4 is essential for efficient sperm-zona pellucida binding <i>in vitro</i>.

Similar Datasets

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