Patients with acephalic spermatozoa syndrome linked to SUN5 mutations have a favorable pregnancy outcome from ICSI

Fang, Jianzheng; Zhang, Jingjing; Zhu, Fuxi; Yang, Xiaoyu; Cui, Yugui; Liu, Jiayin

doi:10.1093/humrep/dex382

Cited by 35 publications

(25 citation statements)

References 11 publications

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“…Indeed, SUN5 appears to be essential in the anchoring of the sperm tail to the head, which results in complete detachment in Sun5 knockout eSPT [ 140 ]. This phenotype appears in accordance with several cases of male infertility due to Sun5 gene mutations that induce SUN5 loss or variant production associated to acephalic SPZ syndrome, a form of teratozoospermia characterized by headless SPZ in the ejaculate [ 146 , 147 , 148 ].…”

Section: Linc Complex and Male Infertilitysupporting

confidence: 76%

LINCking the Nuclear Envelope to Sperm Architecture

Manfrevola

Guillou

Fasano

et al. 2021

Genes

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Nuclear architecture undergoes an extensive remodeling during spermatogenesis, especially at levels of spermatocytes (SPC) and spermatids (SPT). Interestingly, typical events of spermiogenesis, such as nuclear elongation, acrosome biogenesis, and flagellum formation, need a functional cooperation between proteins of the nuclear envelope and acroplaxome/manchette structures. In addition, nuclear envelope plays a key role in chromosome distribution. In this scenario, special attention has been focused on the LINC (linker of nucleoskeleton and cytoskeleton) complex, a nuclear envelope-bridge structure involved in the connection of the nucleoskeleton to the cytoskeleton, governing mechanotransduction. It includes two integral proteins: KASH- and SUN-domain proteins, on the outer (ONM) and inner (INM) nuclear membrane, respectively. The LINC complex is involved in several functions fundamental to the correct development of sperm cells such as head formation and head to tail connection, and, therefore, it seems to be important in determining male fertility. This review provides a global overview of the main LINC complex components, with a special attention to their subcellular localization in sperm cells, their roles in the regulation of sperm morphological maturation, and, lastly, LINC complex alterations associated to male infertility.

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Section: Linc Complex and Male Infertilitysupporting

confidence: 76%

LINCking the Nuclear Envelope to Sperm Architecture

Manfrevola

Guillou

Fasano

et al. 2021

Genes

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“…Previous studies showed that patients with acephalic spermatozoa harboring SUN5 mutations have a good pregnancy outcome after ICSI treatment . However, pregnancy was not achieved after embryo transfer in the woman whose husband harbors a TSGA10 mutation .…”

Section: Discussionmentioning

confidence: 99%

Biallelic mutations in PMFBP1 cause acephalic spermatozoa

Sha

Wang

et al. 2018

Clinical Genetics

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The majority of men with defects in spermatogenesis remain undiagnosed. Acephalic spermatozoa is one of the diseases causing primary infertility. However, the causes underlying over half of affected cases remain unclear. Here, we report by whole‐exome sequencing the identification of homozygous and compound heterozygous truncating mutations in PMFBP1 of two unrelated individuals with acephalic spermatozoa. PMFBP1 was highly and specifically expressed in human and mouse testis. Furthermore, immunofluorescence staining in sperm from a normal control showed that PMFBP1 localizes to the head‐flagella junction region, and the absence of PMFBP1 was confirmed in patients harboring PMFBP1 mutations. In addition, we generated Pmfbp1 knock‐out (KO) mice, which we found recapitulate the acephalic sperm phenotype. Label‐free quantitative proteomic analysis of testicular sperm from Pmfbp1 KO and control mice showed 124 and 35 proteins, respectively, increased or decreased in sperm from KO mice compared to that found in control mice. Gene ontology analysis indicates that the biological process of Golgi vesicle transport was the most highly enriched in differentially expressed proteins, indicating process defects related to Golgi complex function may disturb formation of the head‐neck junction. Collectively, our data indicate that PMFBP1 is necessary for sperm morphology in both humans and mice, and that biallelic truncating mutations in PMFBP1 cause acephalic spermatozoa.

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“…Intracytoplasmic sperm injection (ICSI) is the only technique so far in which abnormal or immotile sperm have the opportunity to fertilise oocytes successfully [13,14]. Meanwhile, Sha et al [11] believed that ICSI was the only solution to AS defects; however, not all AS-deficient sperm achieved the same clinical results [15].…”

Section: Introductionmentioning

confidence: 99%

Beyond Acephalic Spermatozoa: The Complexity of Intracytoplasmic Sperm Injection Outcomes

Nie¹,

Tang²,

Qin³

2020

BioMed Research International

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This review analyses the genetic mechanisms of acephalic spermatozoa (AS) defects, which are associated with primary infertility in men. Several target genes of headless sperms have been identified but intracytoplasmic sperm injection (ICSI) outcomes are complex. Based on electron microscopic observations, broken points of the sperm neck are AS defects that are based on various genes that can be classified into three subtypes: HOOK1, SUN5, and PMFBP1 genes of subtype II; TSGA10 and BRDT genes of subgroup III, while the genetic mechanism(s) and aetiology of AS defects of subtype I have not been described and remain to be explored. Interestingly, all AS sperm of subtype II achieved better ICSI outcomes than other subtypes, resulting in clinical pregnancies and live births. For subtype III, the failure of clinical pregnancy can be explained by the defects of paternal centrioles that arrest embryonic development; for subtype I, this was due to a lack of a distal centriole. Consequently, the embryo quality and potential ICSI results of AS defects can be predicted by the subtypes of AS defects. However, this conclusion with regard to ICSI outcomes based on subtypes still needs further research, while the existence of quality of oocyte and implantation failure in women cannot be ignored.

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Patients with acephalic spermatozoa syndrome linked to SUN5 mutations have a favorable pregnancy outcome from ICSI

Cited by 35 publications

References 11 publications

LINCking the Nuclear Envelope to Sperm Architecture

LINCking the Nuclear Envelope to Sperm Architecture

Biallelic mutations in PMFBP1 cause acephalic spermatozoa

Beyond Acephalic Spermatozoa: The Complexity of Intracytoplasmic Sperm Injection Outcomes

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